Friday, June 30, 2023

New forms of Oral Polio Virus


“We’ve designed these new vaccines using lessons learned from many years of fighting polio and believe they will help eliminate the disease once and for all,” Andino says. “If there’s polio anywhere, it will come back where there are gaps in vaccination. The perception that polio is gone is a dangerous one.”

‘Reckless in the Extreme’: FDA Panel Recommends New RSV Shot for Use in Healthy Infants • Children's Health Defense Fund

Treatment options continue to expand

To create the new vaccines, the researchers used the molecular backbone of their earlier vaccine for the type 2 virus. They retained the genetic components that help keep the weakened virus from becoming pathogenic. But they replaced coding regions for the virus capsid (shell) unique to the type 2 virus with sequences from the other two polio types.


Time has shown critics were wrong.  This is only the beginning of a tug of war as others pursue gains from Pfizer-Moderna.

The oral polio vaccine is often used in resource-poor regions, due to its lower cost and easy delivery. The oral vaccine is also more effective in many ways, but it has a significant drawback: It is based on a live weakened poliovirus that can mutate and evolve. In rare cases, it can become infectious. This can lead to a vaccine-derived outbreak in communities with many unvaccinated people. There are three poliovirus types, with only type one still spreading in the wild. But episodes of all three types can still occur because of the vaccines.

Studies in mice showed that both novel vaccines triggered strong immune responses similar to those seen with the current oral vaccines. Each effectively prevented infection after exposure to the poliovirus. 


Since then, more than 600 million doses of the vaccine have been used to treat polio outbreaks in 28 countries. In their latest study, the researchers created modified oral vaccines that target the other two polioviruses, types 1 and 3. Research to develop the vaccines was supported in part by NIH. Results appeared in Nature on June 14, 2023.


Polio – a disease many have prematurely consigned to history – made headlines around the world in recent months when the virus was detected in relatively high-income country settings from New York, London, Montreal, and Jerusalem. This apparent comeback in polio-free countries has left many questioning the feasibility of eradication. On the contrary, we have never been closer to achieving our goal of a polio-free world: this resurgence only underscores the urgent need for eradication.

When the Global Polio Eradication Initiative (GPEI) was launched in 1988, nearly 1,000 children were being paralyzed with wild poliovirus (WPV) infection across 125 countries every single day. Since then, a concerted effort of health workers, communities, local governments, and global partners such as Rotary International has helped eradicate two of the three serotypes of wild poliovirus (WPV2 and WPV3) and cornered the remaining strain of WPV – type 1 (WPV1) – to small areas of Pakistan and Afghanistan – the last wild polio-endemic countries. The genetic diversity of the remaining chains of WPV1 is also on the decline, indicating the virus might very well be on the verge of being wiped out.  

However, this incredible progress is in jeopardy. Due in part to the COVID-19 pandemic, the world has seen a worrying drop in immunization rates over the past few years, creating pockets of under-immunized communities at heightened risk of polio infection and paralysis. Children missing polio vaccinations create opportunities for polio to re-emerge and spread – as seen in 2022 when WPV1 originating in Pakistan was detected in paralyzed children in Malawi and Mozambique. This episode served as a poignant reminder that as long as polio exists anywhere in the world, it remains a threat to people everywhere.

Persistently under-vaccinated communities are also at risk of outbreaks of vaccine-derived poliovirus (VDPVs). These polio variants evolve from oral polio vaccines (OPVs), which use a weakened form of the virus to protect children from infection and act as a key tool for many countries to stop the spread of polio. When a vaccinated child sheds that weakened virus into the environment, it can help provide indirect protection for the entire community. However, in areas with persistently low immunization coverage, the weakened vaccine virus can circulate over a prolonged period, ultimately regaining the ability to cause paralytic outbreaks that can spread across geographies. 

What do we do about it?

One technological solution to the VDPV situation is the development of OPV strains that are more genetically stable and therefore less likely to evolve into VDPVs. In 2011, a scientific consortium was formed to explore the development of a next-generation vaccine while still maintaining the advantages of existing OPV, such as ease of delivery and intestinal mucosal immunogenicity. As poliovirus serotype 2 strain has been associated with most of the paralytic polio outbreaks of cVDPVs, a new, type 2 OPV was selected as the initial focus of the consortium.

In November 2020, the novel oral polio vaccine type 2 (nOPV2) was authorized under the Emergency Use Listing (EUL) pathway by the World Health Organization (WHO) following positive findings from phase I and phase II studies of safety, reactogenicity, immunogenicity, and the desired genetic stability. The rollout of nOPV2 for outbreak response began in March 2021 and since then, more than 580 million doses of nOPV2 have been delivered in 28 countries, with surveillance data from initial field use indicating a high likelihood of success at closing outbreaks with a lower risk of seeding the emergence of new ones.

Regardless of which polio vaccine is used to stop an outbreak, there must be high immunization coverage for all children to be protected against paralysis. Following the detection of an environmental sample or confirmation of a case of paralytic polio, outbreak response campaigns must be launched in a timely manner to reach all at-risk communities with vaccines. Coordination transcending geographic borders is also key, which is why countries currently at a high risk of polio spread – such as Pakistan and Afghanistan as well as Malawi, Mozambique, Tanzania, Zambia, and Zimbabwe – are synchronizing campaigns to help ensure that underserved and migrant communities are not missed. Readiness on the regulatory front to use a vaccine under EUL provisions as in the case of nOPV2 and maintaining adequate global supplies of such vaccines will be important in minimizing the risk of the spread of polio.

https://pubmed.ncbi.nlm.nih.gov/25824845/

https://pubmed.ncbi.nlm.nih.gov/32330425/

https://pubmed.ncbi.nlm.nih.gov/37317297/

https://pubmed.ncbi.nlm.nih.gov/24175215/


Wednesday, June 28, 2023

Novel vaccines may help quell polio outbreaks | National Institutes of Health (NIH)

In the mid-1900s, the highly contagious disease poliomyelitis, or polio, was responsible for about a half-million cases of paralysis or death worldwide each year. Polio outbreaks began to drop dramatically beginning in the 1950s, after the development of two effective vaccines—one given orally, the other by injection. But despite worldwide efforts to eliminate polio, a few pockets of infection still remain, especially in developing countries.

The oral polio vaccine is often used in resource-poor regions, due to its lower cost and easy delivery. The oral vaccine is also more effective in many ways, but it has a significant drawback: It is based on a live weakened poliovirus that can mutate and evolve. In rare cases, it can become infectious. This can lead to a vaccine-derived outbreak in communities with many unvaccinated people. There are three types of poliovirus, with only type one still spreading in the wild. But outbreaks of all three types can still occur because of the vaccines.



An international research team has been seeking ways to improve the safety of the oral polio vaccine. The team is led by Drs. Raul Andino of the University of California, San Francisco, and Andrew Macadam of the U.K.’s National Institute for Biological Standards and Control. In 2020, they reported on modifications to the oral vaccine for type 2 poliovirus that made it genetically more stable. That means it was less likely to mutate, evolve, and become infectious. That same year, the World Health Organization approved the vaccine for emergency use.

Since then, more than 600 million doses of the vaccine have been used to treat polio outbreaks in 28 countries. In their latest study, the researchers created modified oral vaccines that target the other two polioviruses, types 1 and 3. Research to develop the vaccines was supported in part by NIH. Results appeared in Nature on June 14, 2023.

To create the new vaccines, the researchers used the molecular backbone of their earlier vaccine for the type 2 virus. They retained the genetic components that help keep the weakened virus from becoming pathogenic. But they replaced coding regions for the virus capsid (shell) that are unique to the type 2 virus with sequences from the other two polio types.

Studies in mice showed that both novel vaccines triggered strong immune responses similar to those seen with the current oral vaccines. Each effectively prevented infection after exposure to the poliovirus.

Further study showed that the new vaccines were genetically stable and so unlikely to evolve. The vaccines prevented infection even when packaged together to target two or all three types of poliovirus at once. The finding suggests that a combination vaccine could target all three strains and enable broad protection from poliovirus via an oral vaccine.

“We’ve designed these new vaccines using lessons learned from many years of fighting polio and believe they will help eliminate the disease once and for all,” Andino says. “If there’s polio anywhere, it will come back where there are gaps in vaccination. The perception that polio is gone is a dangerous one.”













Novel vaccines may help quell polio outbreaks | National Institutes of Health (NIH)

Monday, June 26, 2023

Rabbinical Wisdom and Covid

 


The Truth about COVID Vaccines



Wednesday, June 21, 2023

Advanced Treatments for Refractory Treatment of Epilepsy

Advances in epilepsy diagnostics, and treatment return man to quality of life


For years, Eric Walthall of Woodville, Wisconsin, experienced more than 100 debilitating epileptic seizures a month. For more than 20 years, he couldn’t drive. He stopped attending many of his sons' activities because he feared a seizure would cause him to lose consciousness. He separated his shoulder twice and hit his head because seizures caused him to fall.


"I couldn't get through life much more," says Eric, now 53, who was diagnosed with epilepsy at 16. He had tried several medications and procedures, seeking care in five different states, with limited success over more than 30 years.

Still, when Eric came to Mayo Clinic in 2021, he had hope. "I knew Mayo was going to knock it out of the park," says Eric, who is seizure-free after extensive evaluation and eventual surgery.

Eric's complicated case was reported in Epilepsy & Behavior Reports. His treatment included radiofrequency ablation with high electrical current guided by stereoelectroencephalography (SEEG), which uses electrodes placed directly into Eric's brain to find where seizures originate.

Treatment options continue to expand

"Mr. Walthall's case was extraordinarily complex and required close teamwork from a multidisciplinary team," says Brian Lundstrom, M.D., Ph.D., Mayo Clinic neurologist and senior researcher on the report. "Fortunately, combined with recent advanced approaches, we were able to find and treat a specific area of Mr. Walthall's brain and control his seizures.”

Epilepsy affects about 50 million people worldwide, according to the World Health Organization. For about a third of people with epilepsy, seizures persist despite use of medication. For some people, surgery to remove brain tissue where their seizures originate is not an option because of the potential risk to brain areas that control speech and movement.

Before coming to Mayo, Eric had tried various epilepsy treatments. He tried two neurostimulation devices that were implanted and ultimately removed — a vagus nerve stimulation (VNS) device and a responsive neurostimulation (RNS) device. While many patients have had success controlling seizures with neurostimulation devices, Eric did not.

He also had undergone extensive evaluations at other medical institutions. Eric's Mayo team incorporated a wide array of data from these previous tests. "It was critical for us to fully incorporate previous data into our current approaches to optimize seizure control for Mr. Walthall and minimize risk to his speech and motor functions from surgery," Dr. Lundstrom says.


Complicated epilepsy case

Kai Miller, M.D., Ph.D., Mayo Clinic neurosurgeon, used SEEG — temporarily putting small electrodes directly into Eric's brain to find the origin of Eric's seizures and help plan personalized treatment options. The Mayo Epilepsy team read the electrical changes in Eric's brain while he was being monitored in the hospital, narrowing the seizures' origin to a specific region of the brain.

Brain mapping of seizure activity
Brain mapping of seizure activity

Then, using the same temporary electrodes, Dr. Miller used a high electrical current called radiofrequency ablation to treat the brain area that the team identified. For some people, radiofrequency ablation will stop the seizures. But if it doesn’t, surgery still may be performed with no additional risk.

For Eric, the radiofrequency ablation treatment helped temporarily, and this was crucial in confirming the location in his brain for further surgery. He did go on to have surgery to remove part of his brain tissue where seizures were originating.

"Radiofrequency ablation allowed us to test the effect of disrupting the brain region where we believed the seizures were starting from, using electrodes that were already in place," Dr. Miller says. "The ablation gave us information to help weigh the benefits and risks of removing brain tissue in an open surgery; we always must balance the likelihood of a cure against possible risks of surgery. I'm thrilled that Eric's seizures have stopped and he's back to enjoying an active life."

Brain mapping

New technology has improved even traditional surgery for epilepsy. During the operation, Eric was awake, which allowed innovative brain mapping — using a Mayo-developed software tool — to ensure the surgery was as precise as could be to help preserve important brain functions, including language and movement.

In the operating room, Dr. Miller stimulated Eric's brain directly. Eric could speak with Dr. Miller and Eva Alden, Ph.D., a Mayo Clinic neuropsychologist, who administered tests to Eric and compared Eric’s presurgery responses to his abilities during the surgery.

"By assessing and monitoring Eric's responses during surgery, I could provide real-time feedback about his cognitive performance," Dr. Alden says. "This helped Dr. Miller gauge whether it was safe to continue operating in that part of the brain, or whether removing it could potentially result in a functional deficit of language or movement."

Eric recovered in the hospital for a week and had speech and occupational therapy.

'This is a blessing now

Today, Eric is back to driving. He and his wife, Melissa — Eric's chauffeur for years — are figuring out their new normal. Eric was able to take a trip to Canada last fall with his hunting buddies. He returned to downhill skiing, a hobby he had given up. Most importantly, he's able to enjoy family time, in the stands at his younger son's high school basketball games or visiting his older son in college.

"There was a lot of emotional pain and suffering, missing out over the years," says Eric, adding, "This is a blessing now. I give all the credit for my healing to my faith in God and the support of my family and friends and doctors."

For Eric, seeing someone else experience a seizure inspired him to share his story. Once, in a patient reception area, he saw a young girl convulse with a seizure. "Boom, she had one. My eyes welled up. I thought, 'If I ever get better, I want to be an ambassador to show what's possible.'"

The realm of what's possible for patients with epilepsy continues to expand, notes Dr. Lundstrom. Including RNS and VNS, there are other forms of stimulation including noninvasive stimulation and deep brain stimulation for epilepsy. In addition to radiofrequency ablation, there are minimally invasive lasers and guided ultrasound treatment. New research includes studies to predict seizures using wearables, like a smartwatch.

"From a research perspective, it is very exciting to see new diagnostic and therapeutic approaches developed every year," Dr. Lundstrom says. "Even better, though, is to see the difference they can make in a patient's life."

Wednesday, June 14, 2023

How Artificial Intelligence such as ChatGPT will aid in Cancer Treatments

This content was generated by ChatGPT4


The use of artificial intelligence (AI) in the prognosis for cancer has shown great promise in improving the management of cancer patients. AI techniques, such as machine learning and deep learning, have the potential to analyze large amounts of data derived from multi-omics analyses and assist in decision-making processes related to cancer diagnosis, prognosis, and treatment [[1](https://www.nature.com/articles/s41416-021-01633-1)][[3](https://pubmed.ncbi.nlm.nih.gov/31830558/)].


AI in precision oncology is transforming the current approach by integrating data from various sources, including genomics, imaging, and clinical information. These techniques enable the identification of patterns and interactions that may be difficult to detect through traditional methods [[1](https://www.nature.com/articles/s41416-021-01633-1)]. Radiomics, a field within AI, focuses on extracting quantitative features from medical images, such as CT scans and MRI, to create predictive models for cancer diagnosis and prognosis. Radiomics-based AI models have shown promise in predicting cancer outcomes and guiding treatment decisions [[2](https://www.nature.com/articles/s41571-021-00560-7)].


By leveraging AI algorithms, researchers and clinicians can develop predictive models that consider multiple factors and biomarkers, providing a more accurate prognosis for cancer patients. These models can help in assessing disease progression, determining the risk of recurrence, and guiding personalized treatment plans [[3](https://pubmed.ncbi.nlm.nih.gov/31830558/)].


Some specific applications of AI in cancer prognosis include:


1. Cancer Detection and Screening: AI algorithms can assist in the detection of cancer by analyzing medical imaging data. Deep learning models have demonstrated high accuracy in detecting lung nodules in chest radiographs [[2](https://www.nature.com/articles/s41571-021-00560-7)]. AI-based screening systems have also been evaluated for breast cancer screening, showing potential in improving detection rates [[2](https://www.nature.com/articles/s41571-021-00560-7)].


2. Prognostic Prediction: AI models can help predict the prognosis of cancer patients by analyzing various clinical and molecular features. These models take into account factors such as tumor characteristics, genomic profiles, and clinical data to estimate the likelihood of disease progression and overall survival [[1](https://www.nature.com/articles/s41416-021-01633-1)][[3](https://pubmed.ncbi.nlm.nih.gov/31830558/)].


3. Treatment Response Assessment: AI techniques can aid in assessing treatment response and distinguishing between true disease progression and pseudoprogression (an imaging phenomenon that mimics tumor growth). This information can guide treatment decisions and prevent unnecessary interventions [[2](https://www.nature.com/articles/s41571-021-00560-7)].


While AI shows great potential in improving cancer prognosis, there are challenges to be addressed. The development and validation of robust AI models require large and diverse datasets, access to high-quality data, and careful consideration of ethical and regulatory aspects. Integration of AI into clinical practice also requires careful validation, standardization, and ongoing refinement to ensure its reliability and effectiveness [[3](https://pubmed.ncbi.nlm.nih.gov/31830558/)].


In conclusion, the use of AI in prognosis for cancer holds promise for improving patient outcomes. AI techniques, such as machine learning and deep learning, can analyze complex data sets and provide valuable insights for personalized treatment strategies. Continued research and development in this field have the potential to revolutionize cancer care and enhance the accuracy of prognosis prediction in the future.

Monday, June 12, 2023

Medical Freedom Panel 2023 - Senator Mastriano- State of Pennsylvania


The. legislature of the Commonwealth of Pennsylvania wants to pass a "Medical Freedom Act". Currently, eleven states have passed “safe harbor” practitioner exemption laws in some form, including Minnesota, Rhode Island, California, Louisiana, Idaho, Oklahoma, Arizona (for homeopaths), New Mexico, Colorado, Nevada, and, most recently, Maine.

The committee had a hearing which included several patients and medical experts to testify about Covid19 and the Federal and employer mandates regarding COVID vaccination in regard to work, airline travel, and in public spaces.

The testimony is documented in the video HERE.

On June 9, 2023,  Senator Mastriano of the Pennsylvania House of Representatives sponsored a hearing in which Peter McCullough, MD MPH testified with compelling information before the committee.  At the outset (2021) of the pandemic, Dr. McCullough was widely criticized as a right-wing anti-vaxxer. Despite his legitimate medical and academic career, he was lumped in with all other COVID non-experts.

Time has shown critics were wrong.

The topic of the hearing was the illegal mandate for vaccinations using an unproven and non-approved vaccine. Testimony from several patients who were victims of the adverse events from mRNA vaccines.  Citizens were denied employment, refused entry into public spaces, and forced to wear masks (which has been shown not to decrease the spread of viral particles.


Dr. McCullough’s testimony is clear and concise and deconstructs the enormous amounts of unproven data regarding COVID.

There is a clear paper trail for support by the NIH in a gain of function research for SARS-COVID dating back to the 1970s.  The virus was studied at the Wuhan Viral Laboratory in a level 4 biohazard facility. Their study was clearly funded by the NIH, Francis Collins, and Anthony Fauci.  In essence, COVID-19 was produced by the United States and you, the taxpayer.  IT WAS NOT A CHINESE VIRUS.  The Federal government knew that developing biomedical weapons was outlawed by international law and sought to disguise it by offshoring the project yet underwriting its activities.

During a state of crisis, largely induced by media coverage and support by the CDC, vaccines were rushed into production using a technique named mRNA to produce a ‘spike protein’.  mRNA protein production was developed over a decade ago. However, it had never undergone controlled clinical trials (RCT). The metabolic pathway was poorly understood, nor was the biochemistry of its byproducts or detoxification path in humans. Protein spikes remain in the bloodstream for an unknown period. 


In addition to the immunogenic effect allowing viral particles entry into cells, the spike protein has intracellular effects and also persists for a lengthy period in circulation.  This effect is now demonstrated by the syndrome colloquially known as ‘Long Haul Covid’.



The United States has the highest death rate despite being a wealthy nation. Developing nations where vaccination rates were low or non-existent had low death rates from vaccination.  (This may be a statistical anomaly due to poor or nonexistent reporting.). 

Numerous experts have reported these outcomes but were suppressed until recently. Unfortunately, this has not been reported by major media sources that ignore new information.  My readers can find these sources through any internet search for “VAERS” The raw data about COVID vaccination  adverse reactions can be accessed HERE





















Medical Freedom Panel 2023 - Senator Mastriano

Friday, June 9, 2023

‘Reckless in the Extreme’: FDA Panel Recommends New RSV Shot for Use in Healthy Infants • Children's Health Defense

Reckless in the Extreme’: FDA Panel Recommends New RSV Shot for Use in Healthy Infants

Advisors to the U.S. Food and Drug Administration on Thursday recommended approval of AstraZeneca’s new monoclonal antibody, which the drugmaker said is designed to protect infants and toddlers up to age 2 from respiratory syncytial virus, but medical experts interviewed by The Defender called the move “reckless” and “preposterous.”


RSV (Respiratory Syncytial Virus) is a common respiratory virus that typically causes mild, cold-like symptoms in older children and adults. However, RSV can be more serious in infants, particularly those younger than six months old. In fact, RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lungs) and pneumonia in infants.

The severity of RSV in infants can vary. Some infants may only experience mild symptoms, such as a runny nose, cough, and low-grade fever, similar to a common cold. However, in other cases, RSV can lead to more severe respiratory symptoms, including:

1. Rapid or difficult breathing: Infants may breathe rapidly, struggle to catch their breath, or show signs of labored breathing.
2. Wheezing: RSV can cause wheezing, which is a high-pitched whistling sound during breathing.
3. Cyanosis: Infants with severe RSV infection may develop a bluish coloration of the lips, face, or fingernails due to inadequate oxygen supply.
4. Poor feeding: Infants may have difficulty feeding or show a decrease in appetite due to breathing difficulties.
5. Dehydration: Severe RSV infection can lead to dehydration if the infant is unable to take in enough fluids.

Certain factors can increase the risk of severe RSV infection in infants, including premature birth, a weakened immune system, and underlying medical conditions such as congenital heart disease or chronic lung disease.

If you suspect that your infant has RSV or is experiencing severe respiratory symptoms, it's essential to seek medical attention promptly. Healthcare professionals can evaluate the severity of the infection, provide supportive care, and monitor the infant's breathing and overall condition. In severe cases, hospitalization may be required for infants with significant breathing difficulties or dehydration.

Prevention is also crucial in reducing the risk of RSV in infants. Practicing good hand hygiene, avoiding close contact with sick individuals, and keeping infants away from crowded places during the RSV season (typically fall and winter in temperate climates) can help minimize the risk of infection. Additionally, certain high-risk infants may be eligible for palivizumab medication, which can provide temporary protection against severe RSV disease. It's important to consult with a healthcare professional to determine if your infant is a candidate for this preventive treatment.

Remember, if you have concerns about your infant's health or suspect RSV, it's always best to consult with a healthcare professional for an accurate diagnosis and appropriate management.

Here we go again !  99% of infants who contract RSV have cold-like signs and symptoms. 

Advisors to the U.S. Food and Drug Administration (FDA) on Thursday recommended approval of AstraZeneca’s new monoclonal antibody, which the drugmaker said is designed to protect infants and toddlers up to age 2 from respiratory syncytial virus (RSV).

Monoclonal antibodies are not vaccines and do not give long-lasting immunity, but only last as long as t he synthetic antibody is present.  The titers decrease rapidly and must be given annually

The drug, nirsevimab, would be delivered to newborns in a single shot at birth or “just before the start of a baby’s first RSV season, or as a larger dose in a second RSV season in children who are highly vulnerable,” CNN reported.

Here lies another COVID scenario, overreacting to a perceived nonexistent threat.

Common sense on the part of pediatricians should make this 'shot' unnecessary in almost all cases. Some children with serious pulmonary problems, such as cystic fibrosis, would be suitable for this prophylactic drug.

But medical experts interviewed by The Defender raised a number of concerns, including what they said was inadequate safety testing.

“It’s preposterous to give this drug prophylactically, especially without adequate safety testing,” said Brian Hooker, Ph.D., P.E., senior director of science and research for Children’s Health Defense (CHD).

AstraZeneca reported only 48% efficacy for the drug. And Hooker noted that the “circulating half-life of the antibodies is probably less than one month, so the protection would be minimal at best.”

Hooker also commented on the fact that 12 infant deaths were recorded during the clinical trial, which the FDA committee claimed were “unrelated” to the antibody:

“It appears that this vote was meant to bolster the uptake and popularity of the RSV vaccines that are now approved for maternal use. The very low rate of effectiveness for such a therapy is troubling as the conservative estimate is below 50%, which is usually a hard metric for drug approval.

“Also, it seems odd that four infants in the trial would die of cardiac arrest — with no information given, it leaves one to wonder why these children would die in such a way. Also, there should be further investigation into the two SIDS [sudden infant death syndrome] deaths that occurred during the trial.”
Since the monoclonal AB












‘Reckless in the Extreme’: FDA Panel Recommends New RSV Shot for Use in Healthy Infants • Children's Health Defense

This is the Waste from a Surgery

 Hospitals produce an enormous amount of waste.  Much of it is a biological hazard from infectious diseases, blood products, and as a result of operations.


Most Hospital waste cannot be recycled or reused due to concerns for sterility. At one time, many hospital drapes were cloth and could be reused. Most surgical instruments can be reused except for some unique instruments.  As time has passed, more and more instruments are disposable and can be used only once.

Surgical gloves cannot be reused or recycled, nor can plastic drapes, for the same reasons.
These items are not only used in the operating room but also on the hospital floors and rooms. IV containers are made of polyvinyl.  At one time, glass was used for transfusions.

There is a downside to using reusable items in terms of labor, cleaning, and sterilizing items. This becomes expensive in terms of time and personnel.

Hospital and Medical Waste are divided into Regulated and Non-Regulated. Hospitals usually contract with a Medical Waste Provider.  States such as California identify wastes and how they must be processed.

A hospital would need to perform an evaluation and cost analysis to determine if it would be a cost advantage.  Hospitals have lean operating margins and may have found that waste management depends upon disposable products that are an adverse effect on the environment. 

Thursday, June 8, 2023

Pfizer and Moderna are Circling the Wagons



New York-based Promosome filed separate lawsuits against Moderna and Pfizer, accusing both companies of violating patent protections related to mRNA technology.

In the filings submitted to the Southern District Court of California, Promosome claims that in 2009 company-affiliated scientists “discovered a method for increasing protein expression by making small changes to the mRNA that could affect the amount of protein produced without altering the amino acid sequence encoded by the mRNA.” The technology is based on the discoveries of Promosome CSO Dr. Vincent P. Mauro and the late Nobel Laureate Dr. Gerald M. Edelman of The Scripps Research Institute (TSRI) in La Jolla, California. Leveraging their expertise in the area of mRNA translation resulted in pioneering technologies that Promosome licenses to companies seeking to improve biotherapeutic and bio-industrial protein expression.


COVID Patent Lawsuits

Promosome’s Tuesday filings are the latest in the intellectual property battle over COVID-19 vaccines. n April 2023, Arbutus Biopharma sued Pfizer and BioNTech, alleging that their coronavirus vaccine used proprietary lipid nanoparticle (LNP) technology protected by five patents. The lawsuit claims that the delivery system that Comirnaty uses could not have been produced without Arbutus’ technology.

Alnylam also filed patent infringement lawsuits against Pfizer and Moderna in March 2022, accusing both companies of formulating their vaccines using Alnylam’s proprietary LNP drug delivery technology. Massachusetts Biopharma is seeking “fair compensation” for this infringement.

Moderna and Pfizer are also locked in a legal tussle with each other. In August 2022, Moderna sued Pfizer and BioNTech, claiming that the companies “unlawfully copied Moderna’s inventions, and they have continued to use them without permission,” Shannon Thyme Klinger, chief legal officer of Moderna, said at the time.

Pfizer returned with a countersuit in December 2022, seeking to dismiss Moderna’s lawsuit.

Pfizer, Moderna, and Bionet reaped tremendous profits from research based on the discoveries of Promosome CSO Dr. Vincent P. Mauro and the late Nobel Laureate Dr. Gerald M. Edelman of The Scripps Research Institute (TSRI) in La Jolla, California

This is only the beginning. in a tug of war as others pursue gains from Pfizer-Moderna.

In April 2023, Arbutus Biopharma sued Pfizer and BioNTech, alleging that their coronavirus vaccine used proprietary lipid nanoparticle (LNP) technology protected by five patents. The lawsuit claims that the delivery system that Comirnaty uses could not have been produced without Arbutus’ technology.


Pfizer and Moderna are Circling the Wagons

Saturday, June 3, 2023

How to Reinvent your Health - by Gary Mark Levin


Peter Attia gives a holistic overview of why our health care is so broken. In the past decade, social determinants of health have become a part of the health record. This is a measure of societal impact on your life. Attia has noted when he travels the difference in societal stress from America. America ranks #35 in terms of our overall health, and #55 in terms of life expectancy.

Societal issues such as work/life balance, cooking more at home, eating out less (processed foods), and walking more, as seen in Europe all contribute to life expectancy.

One good measurement of health is longevity. The United States is not a winner in that regard. The only category we are number one in is our expense. From 1980 to 2019, Commonwealth Fund found that the U.S. spent nearly 17 percent on health care as a percentage of its gross domestic product (GDP). Other countries, like Switzerland, the U.K., Australia, Norway, and more, spent well below that but still earned higher healthcare performance scores. The forecast is not good. Our life expectancy is decreasing, and this was true pre-COVID.

Life expectancy has dropped: Why it matters


This chart is for the overall life expectancy for Americans, however, there are large deviations for some demographics.

Here are the states with the largest declines in life expectancy

The U.S. fares significantly worse than other developed countries, with the Commonwealth Fund finding Japan has an average life expectancy of 84.4 years, Spain and Switzerland at 84 years and Canada averaging 82.3 years.

The chart below is another view.


African Americans have consistently lagged in life expectancy although the gap is closing.

Economic Growth and Life Expectancy – Do Wealthier Countries Live Longer?

There are many determinants of longevity, and do not always correlate with income, or race. Nutrition and lifestyle are important as well.

Health expenditure as a percentage of gross domestic product (GDP) in selected countries

Prevention

Certain diseases can be detected, however, no one test detects early disease.

Breast Cancer, Cervical Cancer, Colon Cancer, and Prostate Cancer can be detected early.

Mental health issues are significant factors, depression, suicide, and risky behavior all contribute to premature death. There is little doubt smallpox, poliovirus and measles have been eliminated which has increased longevity in the past century.

There are many things in action that can contribute to improved quality of life and life expectation.


During the past decade, we have progressed from Health 2.0 and Health 3.0. Today we have entered Health 4.0. Despite rapid technological advances such as remote monitoring, electronic health records, and fewer uninsured our life expectancy has decreased. Peter Attia seems to have put all of it together and I hope my article can disseminate his words and a few of my own.

Medical 4.0 is the fourth medical revolution, employing emerging technologies to create significant advancements in healthcare. New medical 4.0 technology has advanced significantly, ranging from mobile computing to cloud computing, over the previous decade and is now ready to be employed as a commercially accessible, networked system. Such things as virtual reality, artificial intelligence, networked hospitals and medical clinics create huge data banks for analysis.

References:

Outlive, The Science and Art of Longevity (Peter Attia)

Amazon Books about Longevity

Measuring biological aging in humans: A quest Aging Cell. 2020 Feb; 19(2): e13080.Published online 2019 Dec 12. doi: 10.1111/acel.13080

Acosta, J. C. , Banito, A. , Wuestefeld, T. , Georgilis, A. , Janich, P. , Morton, J. P. , … Gil, J. (2013). A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nature Cell Biology, 15(8), 978–990. 10.1038/ncb2784 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Agarwal, B. , & Baur, J. A. (2011). Resveratrol and life extension. Annals of the New York Academy of Sciences, 1215, 138–143. 10.1111/j.1749-6632.2010.05850.x [PubMed] [CrossRef] [Google Scholar]

Ahmadbeigi, N. , Soleimani, M. , Vasei, M. , Gheisari, Y. , Mortazavi, Y. , Azadmanesh, K. , … Nardi, N. B. (2013). Isolation, characterization, and transplantation of bone marrow‐derived cell components with hematopoietic stem cell niche properties. Stem Cells and Development, 22(23), 3052–3061. 10.1089/scd.2013.0005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Al Shahrani, M. , Heales, S. , Hargreaves, I. , & Orford, M. (2017). Oxidative stress: Mechanistic insights into inherited mitochondrial disorders and Parkinson’s disease. Journal of Clinical Medicine, 6(11), 100 10.3390/jcm6110100 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Allsopp, R. C. , Vaziri, H. , Patterson, C. , Goldstein, S. , Younglai, E. V. , Futcher, A. B. , … Harley, C. B. (1992). Telomere length predicts replicative capacity of human fibroblasts. Proceedings of the National Academy of Sciences, 89(21), 10114–10118. 10.1073/pnas.89.21.10114 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Anderson, R. M. , Le Couteur, D. G. , & de Cabo, R. (2017). Caloric restriction research: New perspectives on the biology of aging. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 73(1), 1–3. 10.1093/gerona/glx212 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Andreux, P. A. , Blanco‐Bose, W. , Ryu, D. , Burdet, F. , Ibberson, M. , Aebischer, P. , … Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 1(6), 595–603. 10.1038/s42255-019-0073-4 [CrossRef] [Google Scholar]

Andriani, G. A. , Almeida, V. P. , Faggioli, F. , Mauro, M. , Tsai, W. L. , Santambrogio, L. , … Montagna, C. (2016). Whole chromosome instability induces senescence and promotes SASP. Scientific Reports, 6(1), 35218 10.1038/srep35218 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Angelini, F. , Pagano, F. , Bordin, A. , Picchio, V. , De Falco, E. , & Chimenti, I. (2017). Getting old through the blood: Circulating molecules in aging and senescence of cardiovascular regenerative cells. Frontiers in Cardiovascular Medicine, 4, 62 10.3389/fcvm.2017.00062 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Arai, Y. , Martin‐Ruiz, C. M. , Takayama, M. , Abe, Y. , Takebayashi, T. , Koyasu, S. , … von Zglinicki, T. (2015). Inflammation, but not telomere length, predicts successful ageing at extreme old age: A longitudinal study of semi‐supercentenarians. EBioMedicine, 2(10), 1549–1558. 10.1016/j.ebiom.2015.07.029 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Arriola Apelo, S. I. , & Lamming, D. W. (2016). Rapamycin: An InhibiTOR of aging emerges from the soil of Easter Island. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 71(7), 841–849. 10.1093/gerona/glw090 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Avin, B. A. , Umbricht, C. B. , & Zeiger, M. A. (2016). Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review). International Journal of Oncology, 49(6), 2199–2205. 10.3892/ijo.2016.3743 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Bae, T. , Tomasini, L. , Mariani, J. , Zhou, B. , Roychowdhury, T. , Franjic, D. , … Vaccarino, F. M. (2017). Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science, 359(6375), 550–555. 10.1126/science.aan8690 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Baker, D. J. , & Petersen, R. C. (2018). Cellular senescence in brain aging and neurodegenerative diseases: Evidence and perspectives. Journal of Clinical Investigation, 128(4), 1208–1216. 10.1172/jci95145 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Baragetti, A. , Palmen, J. , Garlaschelli, K. , Grigore, L. , Humphries, S. , Catapano, A. L. , … Giuseppe Danilo, N. (2016). Leukocyte telomere length, genetically determined, is causally associated with the progression of carotid Intima‐Media Thickness and incidence of cardiovascular events. Atherosclerosis, 252, e252 10.1016/j.atherosclerosis.2016.07.064 [CrossRef] [Google Scholar]

Barker, D. J. P. , Osmond, C. , Winter, P. D. , Margetts, B. , & Simmonds, S. J. (1989). Weight in infancy and death from ischaemic heart disease. The Lancet, 334(8663), 577–580. 10.1016/s0140-6736(89)90710-1 [PubMed] [CrossRef] [Google Scholar]

Batsis, J. A. , Mackenzie, T. A. , Vasquez, E. , Germain, C. M. , Emeny, R. T. , Rippberger, P. , … Bartels, S. J. (2017). Association of adiposity, telomere length and mortality: Data from the NHANES 1999–2002. International Journal of Obesity, 42(2), 198–204. 10.1038/ijo.2017.202 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Beerman, I. (2017). Accumulation of DNA damage in the aged hematopoietic stem cell compartment. Seminars in Hematology, 54(1), 12–18. 10.1053/j.seminhematol.2016.11.001 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Behrens, Y. L. , Thomay, K. , Hagedorn, M. , Ebersold, J. , Henrich, L. , Nustede, R. , … Göhring, G. (2017). Comparison of different methods for telomere length measurement in whole blood and blood cell subsets: Recommendations for telomere length measurement in hematological diseases. Genes, Chromosomes and Cancer, 56(9), 700–708. 10.1002/gcc.22475 [PubMed] [CrossRef] [Google Scholar]

Bektas, A. , Schurman, S. H. , Sen, R. , & Ferrucci, L. (2018). Aging, inflammation and the environment. Experimental Gerontology, 105, 10–18. 10.1016/j.exger.2017.12.015 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ben‐Shlomo, Y. , Cooper, R. , & Kuh, D. (2016). The last two decades of life course epidemiology, and its relevance for research on ageing. International Journal of Epidemiology, 45(4), 973–988. 10.1093/ije/dyw096 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Berglund, K. , Reynolds, C. A. , Ploner, A. , Gerritsen, L. , Hovatta, I. , Pedersen, N. L. , & Hägg, S. (2016). Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk. Aging, 8(7), 1398–1415. 10.18632/aging.100995 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Berwick, M. , & Vineis, P. (2005). Measuring DNA repair capacity: Small steps. Journal of the National Cancer Institute, 97(2), 84–85. 10.1093/jnci/dji038 [PubMed] [CrossRef] [Google Scholar]

Bhat, R. , Crowe, E. P. , Bitto, A. , Moh, M. , Katsetos, C. D. , Garcia, F. U. , … Torres, C. (2012). Astrocyte senescence as a component of Alzheimer’s disease. PLoS ONE, 7(9), e45069 10.1371/journal.pone.0045069 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Biran, A. , Zada, L. , Abou Karam, P. , Vadai, E. , Roitman, L. , Ovadya, Y. , … Krizhanovsky, V. (2017). Quantitative identification of senescent cells in aging and disease. Aging Cell, 16(4), 661–671. 10.1111/acel.12592 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Bischoff, C. , Petersen, H. C. , Graakjaer, J. , Andersen‐Ranberg, K. , Vaupel, J. W. , Bohr, V. A. , … Christensen, K. (2006). No association between telomere length and survival among the elderly and oldest old. Epidemiology, 17(2), 190–194. 10.1097/01.ede.0000199436.55248.10 [PubMed] [CrossRef] [Google Scholar]

Bjedov, I. , Toivonen, J. M. , Kerr, F. , Slack, C. , Jacobson, J. , Foley, A. , & Partridge, L. (2010). Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster . Cell Metabolism, 11(1), 35–46. 10.1016/j.cmet.2009.11.010 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Blekhman, R. , Man, O. , Herrmann, L. , Boyko, A. R. , Indap, A. , Kosiol, C. , … Przeworski, M. (2008). Natural selection on genes that underlie human disease susceptibility. Current Biology, 18(12), 883–889. 10.1016/j.cub.2008.04.074 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Boccardi, V. , Pelini, L. , Ercolani, S. , Ruggiero, C. , & Mecocci, P. (2015). From cellular senescence to Alzheimer’s disease: The role of telomere shortening. Ageing Research Reviews, 22, 1–8. 10.1016/j.arr.2015.04.003 [PubMed] [CrossRef] [Google Scholar]

Branco, M. R. , Ficz, G. , & Reik, W. (2012). Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nature Reviews Genetics, 13(1), 7–13. 10.1038/nrg3080 [PubMed] [CrossRef] [Google Scholar]

Bu, H. , Wedel, S. , Cavinato, M. , & Jansen‐Dürr, P. (2017). MicroRNA regulation of oxidative stress‐induced cellular senescence. Oxidative Medicine and Cellular Longevity, 2017, 1–12. 10.1155/2017/2398696 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Bygren, L. , Tinghög, P. , Carstensen, J. , Edvinsson, S. , Kaati, G. , Pembrey, M. E. , & Sjöström, M. (2014). Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genetics, 15(1), 12 10.1186/1471-2156-15-12 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Capri, M. , Moreno‐Villanueva, M. , Cevenini, E. , Pini, E. , Scurti, M. , Borelli, V. , … Franceschi, C. (2015). MARK‐AGE population: From the human model to new insights. Mechanisms of Ageing and Development, 151, 13–17. 10.1016/j.mad.2015.03.010 [PubMed] [CrossRef] [Google Scholar]

Cesari, M. , Pérez‐Zepeda, M. U. , & Marzetti, E. (2017). Frailty and multimorbidity: Different ways of thinking about geriatrics. Journal of the American Medical Directors Association, 18(4), 361–364. 10.1016/j.jamda.2016.12.086 [PubMed] [CrossRef] [Google Scholar]

Chang, J. , Wang, Y. , Shao, L. , Laberge, R.‐M. , Demaria, M. , Campisi, J. , … Zhou, D. (2015). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22(1), 78–83. 10.1038/nm.4010 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Chen, B. H. , Marioni, R. E. , Colicino, E. , Peters, M. J. , Ward‐Caviness, C. K. , Tsai, P. C. , … Horvath, S. (2016). DNA methylation‐based measures of biological age: Meta‐analysis predicting time to death. Aging (Albany NY), 8(9), 1844–1865. 10.18632/aging.101020 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Chen, M. Z. , Moily, N. S. , Bridgford, J. L. , Wood, R. J. , Radwan, M. , Smith, T. A. , … Hatters, D. M. (2017). A thiol probe for measuring unfolded protein load and proteostasis in cells. Nature Communications, 8(1), 474 10.1038/s41467-017-00203-5 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Chi, M.‐S. , Lee, C.‐Y. , Huang, S.‐C. , Yang, K.‐L. , Ko, H.‐L. , Chen, Y.‐K. , … Chi, K.‐H. (2015). Double autophagy modulators reduce 2‐deoxyglucose uptake in sarcoma patients. Oncotarget, 6(30), 29808–29817. 10.18632/oncotarget.5060 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Childs, B. G. , Durik, M. , Baker, D. J. , & van Deursen, J. M. (2015). Cellular senescence in aging and age‐related disease: From mechanisms to therapy. Nature Medicine, 21(12), 1424–1435. 10.1038/nm.4000 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Childs, B. G. , Gluscevic, M. , Baker, D. J. , Laberge, R.‐M. , Marquess, D. , Dananberg, J. , & van Deursen, J. M. (2017). Senescent cells: An emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718–735. 10.1038/nrd.2017.116 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Childs, B. G. , Li, H. , & van Deursen, J. M. (2018). Senescent cells: A therapeutic target for cardiovascular disease. Journal of Clinical Investigation, 128(4), 1217–1228. 10.1172/jci95146 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Choi, J.‐H. , Kim, S.‐Y. , Kim, S.‐K. , Kemp, M. G. , & Sancar, A. (2015). An integrated approach for analysis of the DNA damage response in mammalian cells. Journal of Biological Chemistry, 290(48), 28812–28821. 10.1074/jbc.m115.690354 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Choi, S. , Reiter, D. A. , Shardell, M. , Simonsick, E. M. , Studenski, S. , Spencer, R. G. , … Ferrucci, L. (2016). 31P Magnetic Resonance Spectroscopy assessment of muscle bioenergetics as a predictor of gait speed in the Baltimore longitudinal study of aging. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71(12), 1638–1645. 10.1093/gerona/glw059 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Coen, P. M. , Jubrias, S. A. , Distefano, G. , Amati, F. , Mackey, D. C. , Glynn, N. W. , … Goodpaster, B. H. (2012). Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults. The Journals of Gerontology: Series A, 68(4), 447–455. 10.1093/gerona/gls196 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Coggan, A. R. (1995). Muscle biopsy as a tool in the study of aging. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 50, 30–34. [PubMed] [Google Scholar]

Cohen, A. , Morissette‐Thomas, V. , Ferrucci, L. , & Fried, L. (2016). Deep biomarkers of aging are population‐dependent. Aging, 8(9), 2253–2255. 10.18632/aging.101034 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Collins, A. R. (2014). Measuring oxidative damage to DNA and its repair with the comet assay. Biochimica Et Biophysica Acta (BBA) ‐ General Subjects, 1840(2), 794–800. 10.1016/j.bbagen.2013.04.022 [PubMed] [CrossRef] [Google Scholar]

Colquitt, B. M. , Allen, W. E. , Barnea, G. , & Lomvardas, S. (2013). Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity. Proceedings of the National Academy of Sciences, 110(36), 14682–14687. 10.1073/pnas.1302759110 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Consolini, A. E. , Ragone, M. I. , Bonazzola, P. , & Colareda, G. A. (2017). Mitochondrial Bioenergetics During Ischemia and Reperfusion. Adv Exp Med Biol, 982, 141–167. 10.1007/978-3-319-55330-6_8 [PubMed] [CrossRef] [Google Scholar]

Coppé, J.‐P. , Desprez, P.‐Y. , Krtolica, A. , & Campisi, J. (2010). The senescence‐associated secretory phenotype: The dark side of tumor suppression. Annual Review of Pathology: Mechanisms of Disease, 5(1), 99–118. 10.1146/annurev-pathol-121808-102144 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Cuervo, A. M. , Bergamini, E. , Brunk, U. T. , Dröge, W. , Ffrench, M. , & Terman, A. (2005). Autophagy and aging: The importance of maintaining "Clean" cells. Autophagy, 1(3), 131–140. 10.4161/auto.1.3.2017 [PubMed] [CrossRef] [Google Scholar]

Cuervo, A. M. , & Macian, F. (2014). Autophagy and the immune function in aging. Current Opinion in Immunology, 29, 97–104. 10.1016/j.coi.2014.05.006 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Cuervo, A. M. , Wong, E. S. P. , & Martinez‐Vicente, M. (2010). Protein degradation, aggregation, and misfolding. Movement Disorders, 25(S1), S49–S54. 10.1002/mds.22718 [PubMed] [CrossRef] [Google Scholar]

de Haan, G. , & Lazare, S. S. (2017). Aging of hematopoietic stem cells. Blood, 131(5), 479–487. 10.1182/blood-2017-06-746412 [PubMed] [CrossRef] [Google Scholar]

Degerman, S. , Josefsson, M. , Nordin Adolfsson, A. , Wennstedt, S. , Landfors, M. , Haider, Z. , … Adolfsson, R. (2017). Maintained memory in aging is associated with young epigenetic age. Neurobiology of Aging, 55, 167–171. 10.1016/j.neurobiolaging.2017.02.009 [PubMed] [CrossRef] [Google Scholar]

Dexheimer, V. , Mueller, S. , Braatz, F. , & Richter, W. (2011). Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age. PLoS ONE, 6(8), e22980 10.1371/journal.pone.0022980 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Diekman, B. O. , Sessions, G. A. , Collins, J. A. , Knecht, A. K. , Strum, S. L. , Mitin, N. K. , … Sharpless, N. E. (2018). Expression of p16INK 4a is a biomarker of chondrocyte aging but does not cause osteoarthritis. Aging Cell, 17(4), e12771 10.1111/acel.12771 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Dikalov, S. I. , & Harrison, D. G. (2014). Methods for detection of mitochondrial and cellular reactive oxygen species. Antioxidants & Redox Signaling, 20(2), 372–382. 10.1089/ars.2012.4886 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ding, J. , Sidore, C. , Butler, T. J. , Wing, M. K. , Qian, Y. , Meirelles, O. , … Schlessinger, D. (2015). Assessing mitochondrial DNA variation and copy number in lymphocytes of ~2,000 Sardinians using tailored sequencing analysis tools. PLoS Genetics, 11(7), e1005306 10.1371/journal.pgen.1005306 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Eerola, J. , Kananen, L. , Manninen, K. , Hellstrom, O. , Tienari, P. J. , & Hovatta, I. (2010). No evidence for shorter leukocyte telomere length in Parkinson's disease patients. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 65A(11), 1181–1184. 10.1093/gerona/glq125 [PubMed] [CrossRef] [Google Scholar]

Eichler, F. , Duncan, C. , Musolino, P. L. , Orchard, P. J. , De Oliveira, S. , Thrasher, A. J. , … Williams, D. A. (2017). Hematopoietic stem‐cell gene therapy for cerebral adrenoleukodystrophy. New England Journal of Medicine, 377(17), 1630–1638. 10.1056/nejmoa1700554 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Eirin, A. , Saad, A. , Tang, H. , Herrmann, S. M. , Woollard, J. R. , Lerman, A. , … Lerman, L. O. (2016). Urinary mitochondrial DNA copy number identifies chronic renal injury in hypertensive patients. Hypertension, 68(2), 401–410. 10.1161/hypertensionaha.116.07849 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Eisenberg, T. , Knauer, H. , Schauer, A. , Buttner, S. , Ruckenstuhl, C. , Carmona‐Gutierrez, D. , … Madeo, F. (2009). Induction of autophagy by spermidine promotes longevity. Nature Cell Biology, 11(11), 1305–1314. 10.1038/ncb1975 [PubMed] [CrossRef] [Google Scholar]

El‐Chemaly, S. , Cheung, F. , Kotliarov, Y. , O’Brien, K. J. , Gahl, W. A. , Chen, J. , … Gochuico, B. R. (2018). The immunome in two inherited forms of pulmonary fibrosis. Frontiers in Immunology, 9, 76 10.3389/fimmu.2018.00076 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

El‐Chemaly, S. , Taveira‐Dasilva, A. , Goldberg, H. J. , Peters, E. , Haughey, M. , Bienfang, D. , … Henske, E. P. (2017). Sirolimus and autophagy inhibition in lymphangioleiomyomatosis. Chest, 151(6), 1302–1310. 10.1016/j.chest.2017.01.033 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

El‐Zein, R. A. , Monroy, C. M. , Cortes, A. , Spitz, M. R. , Greisinger, A. , & Etzel, C. J. (2010). Rapid method for determination of DNA repair capacity in human peripheral blood lymphocytes amongst smokers. BMC Cancer, 10(1), 439 10.1186/1471-2407-10-439 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Epel, E. S. , Blackburn, E. H. , Lin, J. , Dhabhar, F. S. , Adler, N. E. , Morrow, J. D. , & Cawthon, R. M. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49), 17312–17315. 10.1073/pnas.0407162101 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Evangelou, K. , Lougiakis, N. , Rizou, S. V. , Kotsinas, A. , Kletsas, D. , Muñoz‐Espín, D. , … Gorgoulis, V. G. (2016). Robust, universal biomarker assay to detect senescent cells in biological specimens. Aging Cell, 16(1), 192–197. 10.1111/acel.12545 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fabbri, E. , An, Y. , Zoli, M. , Simonsick, E. M. , Guralnik, J. M. , Bandinelli, S. , … Ferrucci, L. (2014). Aging and the burden of multimorbidity: Associations with inflammatory and anabolic hormonal biomarkers. The Journals of Gerontology: Series A, 70(1), 63–70. 10.1093/gerona/glu127 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fabbri, E. , Chia, C. W. , Spencer, R. G. , Fishbein, K. W. , Reiter, D. A. , Cameron, D. , … Ferrucci, L. (2016). Insulin resistance is associated with reduced mitochondrial oxidative capacity measured by 31P‐magnetic resonance spectroscopy in participants without diabetes from the Baltimore longitudinal study of aging. Diabetes, 66(1), 170–176. 10.2337/db16-0754 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fabbri, E. , Zoli, M. , Gonzalez‐Freire, M. , Salive, M. E. , Studenski, S. A. , & Ferrucci, L. (2015). Aging and multimorbidity: New tasks, priorities, and frontiers for integrated gerontological and clinical research. Journal of the American Medical Directors Association, 16(8), 640–647. 10.1016/j.jamda.2015.03.013 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fan, M. , Chen, W. , Liu, W. , Du, G.‐Q. , Jiang, S.‐L. , Tian, W.‐C. , … Tian, H. (2010). The effect of age on the efficacy of human mesenchymal stem cell transplantation after a myocardial infarction. Rejuvenation Research, 13(4), 429–438. 10.1089/rej.2009.0986 [PubMed] [CrossRef] [Google Scholar]

Fang, L. , Neutzner, A. , Turtschi, S. , Flammer, J. , & Mozaffarieh, M. (2015). Comet Assay as an indirect measure of systemic oxidative stress. Journal of Visualized Experiments, 99, e52763 10.3791/52763 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ferrucci, L. , Corsi, A. , Lauretani, F. , Bandinelli, S. , Bartali, B. , Taub, D. D. , … Longo, D. L. (2005). The origins of age‐related proinflammatory state. Blood, 105(6), 2294–2299. 10.1182/blood-2004-07-2599 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ferrucci, L. , & Fabbri, E. (2018). Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nature Reviews Cardiology, 15(9), 505–522. 10.1038/s41569-018-0064-2 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ferrucci, L. , Harris, T. B. , Guralnik, J. M. , Tracy, R. P. , Corti, M.‐C. , Cohen, H. J. , … Havlik, R. J. (1999). Serum IL‐6 level and the development of disability in older persons. Journal of the American Geriatrics Society, 47(6), 639–646. 10.1111/j.1532-5415.1999.tb01583.x [PubMed] [CrossRef] [Google Scholar]

Ferrucci, L. , Levine, M. E. , Kuo, P. L. , & Simonsick, E. M. (2018). Time and the metrics of aging. Circulation Research, 123(7), 740–744. 10.1161/CIRCRESAHA.118.312816 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Ferrucci, L. , Penninx, B. W. J. H. , Volpato, S. , Harris, T. B. , Bandeen‐Roche, K. , Balfour, J. , … Md, J. M. G. (2002). Change in muscle strength explains accelerated decline of physical function in older women with high interleukin‐6 serum levels. Journal of the American Geriatrics Society, 50(12), 1947–1954. 10.1046/j.1532-5415.2002.50605.x [PubMed] [CrossRef] [Google Scholar]

Franceschi, C. , & Campisi, J. (2014). Chronic inflammation (Inflammaging) and its potential contribution to age‐associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(Suppl. 1), S4–S9. 10.1093/gerona/glu057 [PubMed] [CrossRef] [Google Scholar]

Franco, I. , Johansson, A. , Olsson, K. , Vrtačnik, P. , Lundin, P. , Helgadottir, H. T. , … Eriksson, M. (2018). Somatic mutagenesis in satellite cells associates with human skeletal muscle aging. Nature Communications, 9(1), 800 10.1038/s41467-018-03244-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Friedman, E. M. , Christ, S. L. , & Mroczek, D. K. (2015). Inflammation partially mediates the association of multimorbidity and functional limitations in a national sample of middle‐aged and older adults. Journal of Aging and Health, 27(5), 843–863. 10.1177/0898264315569453 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Fulop, T. , Larbi, A. , Dupuis, G. , Le Page, A. , Frost, E. H. , Cohen, A. A. , … Franceschi, C. (2018). Immunosenescence and inflamm‐aging as two sides of the same coin: Friends or foes? Frontiers in Immunology, 8, 1960 10.3389/fimmu.2017.01960 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Gale, C. R. , Marioni, R. E. , Čukić, I. , Chastin, S. F. , Dall, P. M. , Dontje, M. L. , … Deary, I. J. (2018). The epigenetic clock and objectively measured sedentary and walking behavior in older adults: The Lothian Birth Cohort 1936. Clinical Epigenetics, 10(1), 4 10.1186/s13148-017-0438-z [PMC free article] [PubMed] [CrossRef] [Google Scholar]

García‐Calzón, S. , Gea, A. , Razquin, C. , Corella, D. , Lamuela‐Raventós, R. M. , Martínez, J. A. , … Marti, A. (2013). Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: The PREDIMED‐NAVARRA trial. International Journal of Obesity, 38(2), 177–182. 10.1038/ijo.2013.68 [PubMed] [CrossRef] [Google Scholar]

García‐Prat, L. , Martínez‐Vicente, M. , Perdiguero, E. , Ortet, L. , Rodríguez‐Ubreva, J. , Rebollo, E. , … Muñoz‐Cánoves, P. (2016). Autophagy maintains stemness by preventing senescence. Nature, 529(7584), 37–42. 10.1038/nature16187 [PubMed] [CrossRef] [Google Scholar]

Gensous, N. , Bacalini, M. G. , Pirazzini, C. , Marasco, E. , Giuliani, C. , Ravaioli, F. , … Garagnani, P. (2017). The epigenetic landscape of age‐related diseases: The geroscience perspective. Biogerontology, 18(4), 549–559. 10.1007/s10522-017-9695-7 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

GBD 2017 Disease and Injury Incidence and Prevalence Collaborators . (2016). Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1545–1602. 10.1016/s0140-6736(16)31678-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Godderis, L. , Schouteden, C. , Tabish, A. , Poels, K. , Hoet, P. , Baccarelli, A. A. , & Van Landuyt, K. (2015). Global methylation and hydroxymethylation in DNA from blood and saliva in healthy volunteers. BioMed Research International, 2015, 845041 10.1155/2015/845041 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Goglin, S. E. , Farzaneh‐Far, R. , Epel, E. S. , Lin, J. , Blackburn, E. H. , & Whooley, M. A. (2016). Correction: Change in leukocyte telomere length predicts mortality in patients with stable coronary heart disease from the heart and soul study. PLoS ONE, 11(12), e0168868 10.1371/journal.pone.0168868 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Golpanian, S. , DiFede, D. L. , Khan, A. , Schulman, I. H. , Landin, A. M. , Tompkins, B. A. , … Hare, J. M. (2017). Allogeneic human mesenchymal stem cell infusions for aging frailty. The Journals of Gerontology: Series A, 72(11), 1505–1512. 10.1093/gerona/glx056 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Golpanian, S. , DiFede, D. L. , Pujol, M. V. , Lowery, M. H. , Levis‐Dusseau, S. , Goldstein, B. J. , … Hare, J. M. (2016). Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget, 7(11), 11899–11912. 10.18632/oncotarget.7727 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Gonzales‐Ebsen, A. C. , Gregersen, N. , & Olsen, R. K. (2017). Linking telomere loss and mitochondrial dysfunction in chronic disease. Frontiers in Bioscience (Landmark Ed), 22, 117–127. [PubMed] [Google Scholar]

Gonzalez‐Freire, M. , de Cabo, R. , Bernier, M. , Sollott, S. J. , Fabbri, E. , Navas, P. , & Ferrucci, L. (2015). Reconsidering the role of mitochondria in aging. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 70, 1334–1342. [PMC free article] [PubMed] [Google Scholar]

Gonzalez‐Freire, M. , Scalzo, P. , D'Agostino, J. , Moore, Z. A. , Diaz‐Ruiz, A. , Fabbri, E. , … Ferrucci, L. (2018). Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging. Aging Cell, 17(2), e12725 10.1111/acel.12725 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Greider, C. W. (1998). Telomeres and senescence: The history, the experiment, the future. Current Biology, 8(5), R178–R181. 10.1016/s0960-9822(98)70105-8 [PubMed] [CrossRef] [Google Scholar]

Greider, C. W. (2010). Telomerase discovery: The excitement of putting together pieces of the puzzle (nobel lecture). Angewandte Chemie International Edition, 49(41), 7422–7439. 10.1002/anie.201002408 [PubMed] [CrossRef] [Google Scholar]

Guiding Principles for the Care of Older Adults with Multimorbidity: An Approach for Clinicians . (2012). Guiding principles for the care of older adults with multimorbidity: An approach for clinicians: American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity. Journal of the American Geriatrics Society, 60(10), E1–E25. 10.1111/j.1532-5415.2012.04188.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Gupta, V. K. , Scheunemann, L. , Eisenberg, T. , Mertel, S. , Bhukel, A. , Koemans, T. S. , … Sigrist, S. J. (2013). Restoring polyamines protects from age‐induced memory impairment in an autophagy‐dependent manner. Nature Neuroscience, 16(10), 1453–1460. 10.1038/nn.3512 [PubMed] [CrossRef] [Google Scholar]

Haferkamp, S. , Scurr, L. L. , Becker, T. M. , Frausto, M. , Kefford, R. F. , & Rizos, H. (2009). Oncogene‐induced senescence does not require the p16INK4a or p14ARF melanoma tumor suppressors. Journal of Investigative Dermatology, 129(8), 1983–1991. 10.1038/jid.2009.5 [PubMed] [CrossRef] [Google Scholar]

Hall, B. M. , Balan, V. , Gleiberman, A. S. , Strom, E. , Krasnov, P. , Virtuoso, L. P. , … Gudkov, A. V. (2017). p16(Ink4a) and senescence‐associated β‐galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging, 9(8), 1867–1884. 10.18632/aging.101268 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hamann, I. , & Hartwig, A. (2014). Quantification of DNA repair capacity towards oxidatively damaged DNA in subcellular and cellular systems by a nonradioactive cleavage assay. Methods Mol Biol, 1208, 73–84. 10.1007/978-1-4939-1441-8_6 [PubMed] [CrossRef] [Google Scholar]

Hammadah, M. , Al Mheid, I. , Wilmot, K. , Ramadan, R. , Abdelhadi, N. , Alkhoder, A. , … Vaccarino, V. (2017). Telomere shortening, regenerative capacity, and cardiovascular outcomes. Circulation Research, 120(7), 1130–1138. 10.1161/circresaha.116.309421 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hannum, G. , Guinney, J. , Zhao, L. , Zhang, L. , Hughes, G. , Sadda, S. , … Zhang, K. (2013). Genome‐wide methylation profiles reveal quantitative views of human aging rates. Molecular Cell, 49(2), 359–367. 10.1016/j.molcel.2012.10.016 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hare, J. M. , Fishman, J. E. , Gerstenblith, G. , DiFede Velazquez, D. L. , Zambrano, J. P. , Suncion, V. Y. , … Heldman, A. W. (2012). Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy. JAMA, 308(22), 2369 10.1001/jama.2012.25321 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology, 11(3), 298–300. 10.1093/geronj/11.3.298 [PubMed] [CrossRef] [Google Scholar]

Harman, D. (1972). The biologic clock: The mitochondria? Journal of the American Geriatrics Society, 20(4), 145–147. 10.1111/j.1532-5415.1972.tb00787.x [PubMed] [CrossRef] [Google Scholar]

Harman, D. (2003). The free radical theory of aging. Antioxidants & Redox Signaling, 5(5), 557–561. 10.1089/152308603770310202 [PubMed] [CrossRef] [Google Scholar]

Hayashi, G. , & Cortopassi, G. (2015). Oxidative stress in inherited mitochondrial diseases. Free Radical Biology and Medicine, 88, 10–17. 10.1016/j.freeradbiomed.2015.05.039 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

He, Z. , Bian, J. , Carretta, H. J. , Lee, J. , Hogan, W. R. , Shenkman, E. , & Charness, N. (2018). Prevalence of multiple chronic conditions among older adults in Florida and the United States: Comparative analysis of the OneFlorida Data trust and national inpatient sample. Journal of Medical Internet Research, 20(4), e137 10.2196/jmir.8961 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Heidinger, B. J. , Blount, J. D. , Boner, W. , Griffiths, K. , Metcalfe, N. B. , & Monaghan, P. (2012). Telomere length in early life predicts life span. Obstetrical & Gynecological Survey, 67(5), 283–284. 10.1097/ogx.0b013e3182546dd0 [CrossRef] [Google Scholar]

Herbig, U. , Jobling, W. A. , Chen, B. P. C. , Chen, D. J. , & Sedivy, J. M. (2004). Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. Molecular Cell, 14(4), 501–513. 10.1016/s1097-2765(04)00256-4 [PubMed] [CrossRef] [Google Scholar]

Herranz, N. , & Gil, J. (2018). Mechanisms and functions of cellular senescence. Journal of Clinical Investigation, 128(4), 1238–1246. 10.1172/jci95148 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hewitt, G. , Jurk, D. , Marques, F. D. M. , Correia‐Melo, C. , Hardy, T. , Gackowska, A. , … Passos, J. F. (2012). Telomeres are favoured targets of a persistent DNA damage response in ageing and stress‐induced senescence. Nature Communications, 3(1), 708 10.1038/ncomms1708 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hilmer, S. N. , & Le Couteur, D. G. (2016). Standardized, multidisciplinary approaches for the study of aging biology and for translation of aging interventions. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71(4), 425–426. 10.1093/gerona/glv310 [PubMed] [CrossRef] [Google Scholar]

Hinken, A. C. , & Billin, A. N. (2018). Isolation of Skeletal Muscle Stem Cells for Phenotypic Screens for Modulators of Proliferation. Methods Mol Biol, 1787, 77–86. https://doi.org/0.1007/978-1-4939-7847-2_6 [PubMed] [Google Scholar]

Hoffman, J. M. , Lyu, Y. , Pletcher, S. D. , & Promislow, D. E. L. (2017). Proteomics and metabolomics in ageing research: From biomarkers to systems biology. Essays in Biochemistry, 61(3), 379–388. 10.1042/ebc20160083 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Holloway, G. P. , Holwerda, A. M. , Miotto, P. M. , Dirks, M. L. , Verdijk, L. B. , & van Loon, L. J. C. (2018). Age‐associated impairments in mitochondrial ADP sensitivity contribute to redox stress in senescent human skeletal muscle. Cell Reports, 22(11), 2837–2848. 10.1016/j.celrep.2018.02.069 [PubMed] [CrossRef] [Google Scholar]

Holton, N. W. , Ebenstein, Y. , & Gassman, N. R. (2018). Broad spectrum detection of DNA damage by Repair Assisted Damage Detection (RADD). DNA Repair, 66–67, 42–49. 10.1016/j.dnarep.2018.04.007 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115 10.1186/gb-2013-14-10-r115 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Hughes, M. C. , Ramos, S. V. , Turnbull, P. C. , Nejatbakhsh, A. , Baechler, B. L. , Tahmasebi, H. , … Perry, C. G. R. (2015). Mitochondrial bioenergetics and fiber type assessments in microbiopsy vs. bergstrom percutaneous sampling of human skeletal muscle. Frontiers in Physiology, 6, 360 10.3389/fphys.2015.00360 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Jani, B. D. , Nicholl, B. I. , McQueenie, R. , Connelly, D. T. , Hanlon, P. , Gallacher, K. I. , … Mair, F. S. (2017). Multimorbidity and co‐morbidity in atrial fibrillation and effects on survival: Findings from UK Biobank cohort. EP Europace, 20(FI_3), f329–f336. 10.1093/europace/eux322 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Jim, H. S. L. , Sutton, S. K. , Small, B. J. , Jacobsen, P. B. , Wood, W. A. , Knight, J. M. , … Lee, S. J. (2016). Trajectories of quality of life after hematopoietic cell transplantation: Secondary analysis of blood and marrow transplant clinical trials network 0902 data. Biology of Blood and Marrow Transplantation, 22(11), 2077–2083. 10.1016/j.bbmt.2016.08.012 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Jiménez‐Chillarón, J. C. , Díaz, R. , Martínez, D. , Pentinat, T. , Ramón‐Krauel, M. , Ribó, S. , & Plösch, T. (2012). The role of nutrition on epigenetic modifications and their implications on health. Biochimie, 94(11), 2242–2263. 10.1016/j.biochi.2012.06.012 [PubMed] [CrossRef] [Google Scholar]

Jimenez‐Chillaron, J. C. , Hernandez‐Valencia, M. , Lightner, A. , Faucette, R. R. , Reamer, C. , Przybyla, R. , … Patti, M. E. (2006). Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight. Diabetologia, 49(8), 1974–1984. 10.1007/s00125-006-0311-7 [PubMed] [CrossRef] [Google Scholar]

Jodczyk, S. , Fergusson, D. M. , Horwood, L. J. , Pearson, J. F. , & Kennedy, M. A. (2014). No association between mean telomere length and life stress observed in a 30 year birth cohort. PLoS ONE, 9(5), e97102 10.1371/journal.pone.0097102 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Justice, J. N. , Gregory, H. , Tchkonia, T. , LeBrasseur, N. K. , Kirkland, J. L. , Kritchevsky, S. B. , & Nicklas, B. J. (2018). Cellular senescence biomarker p16INK4a+ cell burden in thigh adipose is associated with poor physical function in older women. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 73(7), 939–945. 10.1093/gerona/glx134 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Jylhävä, J. , Pedersen, N. L. , & Hägg, S. (2017). Biological age predictors. Ebiomedicine, 21, 29–36. 10.1016/j.ebiom.2017.03.046 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Jylhävä, J. , Raitanen, J. , Marttila, S. , Hervonen, A. , Jylhä, M. , & Hurme, M. (2014). Identification of a prognostic signature for old‐age mortality by integrating genome‐wide transcriptomic data with the conventional predictors: The Vitality 90+ Study. BMC Medical Genomics, 7(1), 10.1186/1755-8794-7-54 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kadota, T. , Fujita, Y. , Yoshioka, Y. , Araya, J. , Kuwano, K. , & Ochiya, T. (2018). Emerging role of extracellular vesicles as a senescence‐associated secretory phenotype: Insights into the pathophysiology of lung diseases. Molecular Aspects of Medicine, 60, 92–103. 10.1016/j.mam.2017.11.005 [PubMed] [CrossRef] [Google Scholar]

Kananen, L. , Marttila, S. , Nevalainen, T. , Kummola, L. , Junttila, I. , Mononen, N. , … Jylhävä, J. (2016). The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: Evidence from two longitudinal studies. AGE, 38(3), 65 10.1007/s11357-016-9927-9 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kang, C. , Xu, Q. , Martin, T. D. , Li, M. Z. , Demaria, M. , Aron, L. , … Elledge, S. J. (2015). The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science, 349(6255), aaa5612–aaa5612. 10.1126/science.aaa5612 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kang, E. , Wang, X. , Tippner‐Hedges, R. , Ma, H. , Folmes, C. D. L. , Gutierrez, N. M. , … Mitalipov, S. (2016). Age‐related accumulation of somatic mitochondrial DNA mutations in adult‐derived human iPSCs. Cell Stem Cell, 18(5), 625–636. 10.1016/j.stem.2016.02.005 [PubMed] [CrossRef] [Google Scholar]

Kaushik, S. , & Cuervo, A. M. (2018). The coming of age of chaperone‐mediated autophagy. Nature Reviews Molecular Cell Biology, 19(6), 365–381. 10.1038/s41580-018-0001-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kent, J. A. , & Fitzgerald, L. F. (2016). In vivo mitochondrial function in aging skeletal muscle: Capacity, flux, and patterns of use. Journal of Applied Physiology, 121(4), 996–1003. 10.1152/japplphysiol.00583.2016 [PubMed] [CrossRef] [Google Scholar]

Kim, S. , & Jazwinski, S. M. (2015). Quantitative measures of healthy aging and biological age. Healthy Aging Research, 4, 10.12715/har.2015.4.26 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kirkland, J. L. , & Tchkonia, T. (2017). Cellular senescence: A translational perspective. Ebiomedicine, 21, 21–28. 10.1016/j.ebiom.2017.04.013 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Kirkland, J. L. , Tchkonia, T. , Zhu, Y. , Niedernhofer, L. J. , & Robbins, P. D. (2017). The clinical potential of senolytic drugs. Journal of the American Geriatrics Society, 65(10), 2297–2301. 10.1111/jgs.14969 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Klionsky, D. J. (2014). Coming soon to a journal near you—the updated guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy, 10(10), 1691–1691. 10.4161/auto.36187 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Klionsky, D. J. , Cuervo, A. M. , & Seglen, P. O. (2007). Methods for monitoring autophagy from yeast to human. Autophagy, 3(3), 181–206. 10.4161/auto.3678 [PubMed] [CrossRef] [Google Scholar]

Knight, A. K. , Craig, J. M. , Theda, C. , Baekvad‐Hansen, M. , Bybjerg‐Grauholm, J. , Hansen, C. S. , … Smith, A. K. (2016). An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biology, 17(1), 206 10.1186/s13059-016-1068-z [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Koppelstaetter, C. , Schratzberger, G. , Perco, P. , Hofer, J. , Mark, W. , Ollinger, R. , … Mayer, G. (2008). Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation. Aging Cell, 7(4), 491–497. 10.1111/j.1474-9726.2008.00398.x [PubMed] [CrossRef] [Google Scholar]

Laberge, R.‐M. , Zhou, L. , Sarantos, M. R. , Rodier, F. , Freund, A. , de Keizer, P. L. J. , … Campisi, J. (2012). Glucocorticoids suppress selected components of the senescence‐associated secretory phenotype. Aging Cell, 11(4), 569–578. 10.1111/j.1474-9726.2012.00818.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lanza, I. R. , & Nair, K. S. (2010). Mitochondrial metabolic function assessed in vivo and in vitro. Current Opinion in Clinical Nutrition and Metabolic Care, 13(5), 511–517. 10.1097/mco.0b013e32833cc93d [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lara, J. , Cooper, R. , Nissan, J. , Ginty, A. T. , Khaw, K.‐T. , Deary, I. J. , … Mathers, J. C. (2015). A proposed panel of biomarkers of healthy ageing. BMC Medicine, 13(1), 222 10.1186/s12916-015-0470-9 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Larsen, S. , Nielsen, J. , Hansen, C. N. , Nielsen, L. B. , Wibrand, F. , Stride, N. , … Hey‐Mogensen, M. (2012). Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. The Journal of Physiology, 590(14), 3349–3360. 10.1113/jphysiol.2012.230185 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Larsson, N.‐G. (2010). Somatic mitochondrial DNA mutations in mammalian aging. Annual Review of Biochemistry, 79(1), 683–706. 10.1146/annurev-biochem-060408-093701 [PubMed] [CrossRef] [Google Scholar]

Latimer, J. J. , & Kelly, C. M. (2014). Unscheduled DNA synthesis: the clinical and functional assay for global genomic DNA nucleotide excision repair. Methods Mol Biol, 1105, 511–532. 10.1007/978-1-62703-739-6_36 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lavker, R. M. , & Sun, T. T. (2000). Epidermal stem cells: Properties, markers, and location. Proceedings of the National Academy of Sciences, 97(25), 13473–13475. 10.1073/pnas.250380097 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lee, I. H. , Cao, L. , Mostoslavsky, R. , Lombard, D. B. , Liu, J. , Bruns, N. E. , … Finkel, T. (2008). A role for the NAD‐dependent deacetylase Sirt1 in the regulation of autophagy. Proceedings of the National Academy of Sciences of the United States of America, 105(9), 3374–3379. 10.1073/pnas.0712145105 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lev Maor, G. , Yearim, A. , & Ast, G. (2015). The alternative role of DNA methylation in splicing regulation. Trends in Genetics, 31(5), 274–280. 10.1016/j.tig.2015.03.002 [PubMed] [CrossRef] [Google Scholar]

Levine, M. E. , Lu, A. T. , Quach, A. , Chen, B. H. , Assimes, T. L. , Bandinelli, S. , … Horvath, S. (2018). An epigenetic biomarker of aging for lifespan and healthspan. Aging, 10(4), 573–591. 10.18632/aging.101414 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Li, C. , Gao, W. , Gao, Y. , Yu, C. , Lv, J. , Lv, R. , … Li, L. (2018). Age prediction of children and adolescents aged 6–17 years: An epigenome‐wide analysis of DNA methylation. Aging, 10(5), 1015–1026. 10.18632/aging.101445 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Li, M. , Chen, M. , Han, W. , & Fu, X. (2010). How far are induced pluripotent stem cells from the clinic? Ageing Research Reviews, 9(3), 257–264. 10.1016/j.arr.2010.03.001 [PubMed] [CrossRef] [Google Scholar]

Li, Y. , Huang, J. , Pang, S. , Wang, H. , Zhang, A. , Hawley, R. G. , & Yan, B. (2017). Novel and functional ATG12 gene variants in sporadic Parkinson's disease. Neuroscience Letters, 643, 22–26. 10.1016/j.neulet.2017.02.028 [PubMed] [CrossRef] [Google Scholar]

Ligthart, S. , Marzi, C. , Aslibekyan, S. , Mendelson, M. M. , Conneely, K. N. , Tanaka, T. , … Dehghan, A. (2016). DNA methylation signatures of chronic low‐grade inflammation are associated with complex diseases. Genome Biology, 17(1), 255 10.1186/s13059-016-1119-5 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lin, J. , Cheon, J. , Brown, R. , Coccia, M. , Puterman, E. , Aschbacher, K. , … Blackburn, E. H. (2016). Systematic and cell type‐specific telomere length changes in subsets of lymphocytes. Journal of Immunology Research, 2016, 1–9. 10.1155/2016/5371050 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Lin, Y. , Damjanovic, A. , Metter, E. J. , Nguyen, H. , Truong, T. , Najarro, K. , … Weng, N.‐P. (2015). Age‐associated telomere attrition of lymphocytes in vivo is co‐ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions. Clinical Science, 128(6), 367–377. 10.1042/cs20140481 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Liu, L. , Cheung, T. H. , Charville, G. W. , & Rando, T. A. (2015). Isolation of skeletal muscle stem cells by fluorescence‐activated cell sorting. Nature Protocols, 10(10), 1612–1624. 10.1038/nprot.2015.110 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Liu, Y. , Sanoff, H. K. , Cho, H. , Burd, C. E. , Torrice,















How to Reinvent your Health - by Gary Mark Levin