Dr. Mikhail Blagosklonny on Rapamycin Longevity Series

The world’s leading Rapamycin researcher, Dr. Mikhail Blagosklonny, has a long background in cancer research and one important discovery he made around 2000 was that Rapamycin slowed down senescent cancer cells in different ways. After that step-by-step, his interest in the longevity field increased and he developed the very interesting hyperfunction theory of aging.

He has made a huge contribution in moving the Rapamycin longevity field forward and his research papers have impacted many people. For example, the Rapamycin physician Alan Green who – thanks to these papers – took the decision in 2017 to start prescribing Rapamycin off label. Today, Alan Green has the biggest clinical experience in the area with more than 1,200 patients. A lot of other physicians have after that also taken these steps and one of those, for example, is physician Peter Attia.

Interview Table of Contents:

  • 02:32 Current situation and mission
  • 04:07 Why did Rapamycin not prevent his cancer?
  • 06:33 He develops a new type of cancer treatment
  • 08:32 Hyperfunction theory of age-related diseases
  • 10:38 mTOR drives age-related diseases
  • 13:00 Hyperfunction theory and the car analogy
  • 17:20 Difference between new and old version of hyperfunction theory
  • 19:58 Prediction based on hyperfunction theory
  • 21:38 Rapamycin seems to work at any age
  • 23:55 Rapamycin will not make you immortal
  • 26:21 Rapamycin delays lung cancer in mice
  • 27:44 Hyperfunction theory and hormesis
  • 29:13 Rapamycin combination with fasting or calorie restriction
  • 30:33 Rapamycin combination with Acarbose or low carb diet
  • 31:40 Rapamycin combination with exercise
  • 33:04 Exercise and longevity effect
  • 36:10 mTOR sweet spot
  • 38:44 Why do centenarians live a long life?
  • 40:36 Theory of accumulation of molecular damage
  • 44:04 Hyperfunction theory was initially rejected
  • 47:47 Rapamycin research that is missing
  • 51:44 Rapamycin and bacterial infection
  • 53:30 Rapamycin side effect on longevity dose regime
  • 55:50 Rapamycin and pseudo-diabetes
  • 58:51 Rapamycin combination of Acarbose or low carb diet
  • 1:00:09 Rapamycin and increase in lipids
  • 1:02:19 mTOR, mTORC1 and mTORC2
  • 1:05:22 Mikhail’s self-experimentation with Rapamycin
  • 1:10:41 Rapamycin and traditional medical care
  • 1:11:13 Rapamycin and unacceptable side effects
  • 1:14:26 Rapamycin and combinations to avoid
  • 1:16:55 Rapamycin and high protein intake
  • 1:18:08 Best time to start taking Rapamycin
  • 1:21:00 Does Rapamycin prevent cancer or not?
  • 1:23:52 Autophagy is a double-edged sword
  • 1:26:51 Important insight from his cancer
  • 1:28:38 Rapamycin rebound effect
  • 1:30:24 Difference between theory and practice
  • 1:32:45 Mikhail’s cancer and cancer treatment
  • 1:37:36 Rapamycin and danger

Dr. Blagosklonny’s Links:

Rapamycin resources:

Disclaimer from host Krister Kauppi:

The podcast is for general information and educational purposes only and is not medical advice for you or others. The use of information and materials linked to the podcast is at the users own risk. Always consult your physician with anything you do regarding your health or medical condition.

Aging’s Scientific Integrity Process

The open-access journal Aging recently launched a new webpage showcasing the full Aging Scientific Integrity Process.

Aging banner
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BUFFALO, NY-Novembe8, 2022 – Scientific integrity is a crucial component of scholarly publishing for any credible journal. Peer-reviewed, open-access journal Aging (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) has recently presented its Scientific Integrity process.

Launched in 2009, Aging is an open-access biomedical journal dedicated to publishing high-quality, aging-focused research. Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. 

Aging has a scientific integrity process to ensure that publications meet a number of scrupulous criteria for authenticity and integrity. Each published paper is thoroughly analyzed by diligent reviewers and services, including multiple in-house developed image forensics softwares. A growing industry of digital technologies, tools and ideas are constantly being added to Aging’s scientific integrity toolbox. 

Aging’s Scientific Integrity process is built upon six critical components:

  1. Easily Accessible Ethics Statements
  2. Devotion to Industry Standards for Scientific Publishing
  3. Rigorous and Insightful Peer Review
  4. Detection and Zero-Tolerance of Plagiarism
  5. Leading-Edge Image Forensics
  6. Post-Publication Investigations (if needed)

You can read about each of these components in greater detail on Aging’s new Scientific Integrity webpage

The new webpage also depicts publishing statistics in a detailed graph (below)—showcasing a visual representation of the number of post-publication corrections and retractions by Aging compared to the industry average, between 2010 and 2022. As of September 2022, Aging’s average rate of corrections/retractions since 2009 is a low 2.33%. The industry average correction/retraction rate is 3.80%. 

Image forensics corrections/retractions (published & pending) as a percent of IF-eligible articles in Aging, 2009-2022

Aging’s highly-effective scientific integrity process allows researchers to read, share and cite Aging papers with confidence.

Click here for Aging’s full Scientific Integrity Process.

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Trending With Impact: New Drug Combinations Inhibit Stress Proteins

Researchers tested antiviral, anticancer, and immunosuppressive drug combinations that may aid in treating neurodegenerative disorders, including Alzheimer’s disease.

Figure 5. Neratinib and AR12 combine to reduce the expression of HSP90, HSP70, GRP78 and HSP27 via autophagy.
Figure 5. Neratinib and AR12 combine to reduce the expression of HSP90, HSP70, GRP78 and HSP27 via autophagy.

The Trending with Impact series highlights Aging publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Heat shock proteins (HSPs), also known today as stress proteins, were first observed in fruit flies in the 1960s. After Dr. Ferruccio Ritossa inadvertently subjected a preparation of fruit fly salivary glands to a non-lethal increase in temperature, he discovered a new pattern of chromosomal “puffing.” In 1974, researchers identified the proteins that were encoded by the “puffs” recorded by Dr. Ritossa, and named them heat shock proteins. 

These newfound proteins appeared to only become detectable when the cells were heated. Researchers later learned that HSPs can also be induced by oxidants, toxins, heavy metals, free radicals, viruses, and other stressors. Since its discovery, variations of this genetic system have been found in all bacteria, plants, and animals—including humans. HSPs have been well-studied since this revelation, and researchers now believe these molecular chaperones play important roles in protein refolding, aging-related diseases, and overall longevity. 

“Toxic misfolded proteins are key drivers of AD [Alzheimer’s disease], ALS [Amyotrophic lateral sclerosis], HC [Huntington’s Chorea] and other neurodegenerative diseases.”

Researchers from Virginia Commonwealth UniversityTranslational Genomics Research Institute, and the Banner Alzheimer’s Institute took part in a research study experimenting with combinations of therapeutic agents that may improve neurodegenerative diseases. In 2021, their paper was published in Aging’s Volume 13, Issue 13, and entitled, “Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43.”

“In this paper we examined using isogenic colon cancer cells [with] several existing drugs that function by increasing autophagy and degrading misfolded proteins.”

THE STUDY

“Aberrant expression of chaperone proteins is found in many human pathologies including cancer, in virology and in AD, ALS and HC.”

In this study, researchers tested drugs that have been used preclinically and clinically in several anticancer studies. The drugs used were: AR12, an antiviral chaperone ATPase inhibitor; Neratinib, a tyrosine kinase inhibitor; a combination of AR12 and Neratinib; Fingolimod, an immunosuppressive sphingosine l-phosphate receptor modulator; MMF, monomethyl fumarate; and a combination of Fingolimod and MMF.

The cells they tested these drug combinations on in vitro included Vero cells (African Green Monkey kidney cells), isogenic HCT116 colon cancer cells (genetically manipulated colon cancer cells), and GB6 cells (glioblastoma cancer stem cells). They also used plasmids, antibodies, and siRNAs. Researchers acknowledged that the use of non-neuronal cells may be a limitation of this study.

“Our present studies were performed in non-neuronal cells and as a caveat, it is possible that our data in HCT116 and Vero cells will not be reflective of the same processes in neuronal cells.”

Despite this caveat, results from their research were promising. Some combinations of these drugs were capable of knocking down many disease specific proteins that form toxic aggregates inside cells and in extracellular environments via autophagy. 

CONCLUSION

“As the mechanism of drug-action became clearer it was apparent that these agents should also be tested in neurodegenerative diseases. The entire neurodegenerative field needs rapid translational methods that target the underlying cause of disease, toxic misfolded protein. The findings from this work warrant further testing with a focus on clinical utility.”

Click here to read the full research paper, published by Aging.

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Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.


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Salt Water-Infused Blood Reverses Aging

From the University of California Berkeley and Apheresis Care Group, researchers ​​discovered a method of “refreshing” blood that reverses some of the effects of aging.

Infusion drips with bottles of yellow albumin fluid.
Infusion drips with bottles of yellow albumin fluid.

The Top-Performer series highlights papers published by Aging that have generated a high Altmetric attention score. Altmetric scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

Read Aging’s Top 100 Altmetric papers.

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Is it possible for old blood to be “refreshed” in order to rejuvenate youth and combat the effects of aging? Aging researchers have a long history of analyzing the blood in search of the keys to healthy aging. In 2020, researchers from the University of California Berkeley and Apheresis Care Group uncovered groundbreaking new insights about the rejuvenation of aging blood with the potential to slow, and potentially to reverse, aging. Their well-read priority research paper was published by Aging and entitled, “Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin.” To date, this top-performing paper has generated an impressive Altmetric Attention score of 147.

Blood Plasma

Approximately 55% of the body’s total blood volume is composed of a pale yellow liquid—plasma. Plasma largely consists of water (about 92%), with traces of mineral salts, sugars, fats, hormones, and vitamins. This watery substance also contains important proteins, such as immunoglobulin (antibodies), clotting/coagulation factors, and albumin.

“In people, albumin levels correlate with disease, nutrition, and socio-economic status rather than chronological age; and even when health, etc. status are not considered, albumin diminishes only marginally, by 2-4% at 75 years of age from its 26 years of age levels [2124].”

Plasmapheresis is a general term used to describe procedures that remove, treat, and return or exchange blood plasma to the blood. Patients with autoimmune diseases, sickle cell disease, certain forms of neuropathy, and even severe cases of malaria have benefitted from plasmapheresis. 

Heterochronic Parabiosis

Heterochronic parabiosis, a plasmapheresis-like procedure, is the surgical joining of two organisms in an effort to study the physiological changes that result from shared blood flow. Researchers have used this model of joining young and old animals together to observe the effects of old blood in young mice, and vice versa. In a 2005 study, University of California Berkeley and Apheresis Care Group researchers found that, through the process of heterochronic parabiosis, old mice sharing blood with young mice produced rejuvenating effects in old mice. 

“The general conclusion of these studies was that the old partners had better health and/or repair of cartilage, muscle, liver, brain, spinal cord, kidneys, bone, skin, etc., and often the young animals experienced premature aging of their respective tissues [13468].”

However, the same researchers suspected that the rejuvenating effects demonstrated by heterochronic parabiosis were not direct results of youthful factors in the young murine blood itself. They also suspected that the premature aging experienced by the young mice were not due to old factors in the aged blood either. The team proposed that simply diluting the young and old factors in the blood may be the cause of these effects. In 2020, the researchers conducted a new study, this time using saline and albumin, to test their hypothesis.

“Historically, the phenomena of heterochronic parabiosis and blood exchange remained unconfirmed with respect to the key assumption as to whether the addition of young factors is needed for rejuvenation, and if premature aging of young mice stemmed from the introduction of old blood factors or a simple dilution of young factors.”

The Study

In this study, the researchers began by conducting a plasmapheresis procedure in mice called a neutral blood exchange (NBE). Half of the platelet-rich-plasma (PRP) was removed from the blood in young and old mice and was replaced with a simple saline and 5% purified albumin.

“Through a half-hour long series of small volume exchanges, 50% of the PRP of old and young mice was replaced with saline plus 5% mouse albumin while the circulating red and white blood cells were returned isochronically to the animal.”

Their results showed that a single session of NBE improved regeneration, reduced fibrosis, enhanced myogenesis, and other factors in the old mice. In the young mice, they found that this procedure did not have adverse effects or worsen the aforementioned factors. To verify their findings, the team studied human blood samples from four older individuals (between the ages 65 and 70) and conducted an FDA approved procedure, Therapeutic Plasma Exchange (TPE), using the same saline/albumin formula.

“To confirm these findings and to explore their evolutionary conservation, we took advantage of the fact that there is a procedure for human patients analogous to NBE, where most of the plasma is replaced by physiologic solution supplemented with commercial human albumin, called Therapeutic Plasma Exchange, TPE, which is FDA approved and routinely used in the clinic [1618].”

Conclusion

In summary, their research found that simply diluting old blood factors with a neutral substance such as saline and albumin contributes to improving muscle repair, attenuating fibrosis, enhancing myogenic proliferation, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis. In some areas, they found that these effects were even stronger in TPE than results after heterochronic parabiosis or blood exchange.

“The theoretical significance of this study is in a better understanding of how blood heterochronicity acts to quickly and profoundly rejuvenate old mammals, and the clinical significance of this work is in developing TPE as a new modality to broadly improve organ health and repair in older individuals preventing illnesses that develop or become more severe in later decades of life.”

Click here to read the full priority research paper, published by Aging.

WATCH: MORE AGING VIDEOS ON LABTUBE

Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact media@impactjournals.com.

Trending With Impact: Circulating Mitochondria and Inflamm-Aging

Authors from the National Institute on Aging wrote a trending editorial paper on mitochondria extracellular vesicles and aging.

Figure 1. Mitochondrial DNA in extracellular vesicles and association with human aging.
Figure 1. Mitochondrial DNA in extracellular vesicles and association with human aging.
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The Trending With Impact series highlights Aging publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

Some structures inside cells play elusive, yet important roles in human aging. Researchers believe structures classified as extracellular vesicles (EVs), released outside of cell walls, may also play key components in the aging process—specifically related to chronic inflammation.

“EVs are lipid-bound nano-sized vesicles that are secreted outside of cells into the circulation (Figure 1A).”

Two researchers from the National Institutes of Health‘s National Institute on Aging wrote a trending editorial paper, published by Aging in 2021, and entitled, “Mitochondria as extracellular vesicle cargo in aging.” 

Inflammation and Aging

The term “inflamm-aging” has been coined to describe the common state of chronic low-grade inflammation associated with aging. Researchers believe that inflammation contributes to many age-related diseases, including cardiovascular disease, diabetes, cancer, and even dementia.

“In fact, inflammation-related diseases account for more than 50% of worldwide deaths, stressing the importance of inflammation in driving age-related disease and mortality [1,2].”

In the elderly, cellular damage and stress (among other causes) may contribute to chronic inflammation, which can initiate a release of mitochondrial damage-associated molecular patterns. This process can initiate cells to release mitochondrial DNA (mtDNA) into the space outside of the cell as circulating cell-free mitochondria DNA (ccf-mtDNA).

“Due to the similarities between mtDNA and bacterial DNA, this release can in turn elicit a sterile inflammatory response through activation of the innate immune system.”

Circulating Cell-Free Mitochondria DNA

Authors of this editorial believe that ccf-mtDNA may contribute to systemic chronic inflammation. In a previous study, researchers found, in general, that higher plasma/serum levels of ccf-mtDNA were reported in patients with inflammatory-related diseases and after acute injury or infection. However, ccf-mtDNA’s role in aging is complex, as one study showed that ccf-mtDNA levels initially decline into middle-age, and then gradually increase after age 50. 

The molecular details of how ccf-mtDNA exists within blood circulation has yet to be elucidated. Questions still linger surrounding whether or not components in the blood bind to ccf-mtDNA. If components do bind to ccf-mtDNA, are they capable of protecting ccf-mtDNA from destruction in circulation?

Extracellular Vesicles and mtDNA

“Given these gaps in the field, we recently explored whether plasma mtDNA can be encapsulated in extracellular vesicles (EVs) [5].”

The researchers evaluated multiple studies to find that mtDNA can be encapsulated in EVs isolated from plasma—both in cells that have been grown in vitro and in plasma EVs from patients with breast cancer. The next question the researchers addressed was: How do levels of mtDNA in plasma EVs fair in normal conditions and with age?

“To address this need, we isolated plasma EVs and analyzed mtDNA levels with human age. Individuals in this aging cohort had donated plasma at two different time points approximately 5 years apart, which enabled us to examine both crosssectional and longitudinal changes.”

Conclusion

“In both our cross-sectional and longitudinal analyses, EV mtDNA levels decreased with advancing age [5] (Figure 1B).”

The researchers concluded by reporting EV mtDNA levels decreased over a span of five years in the longitudinal cohort. Mitochondrial components, including mtDNA, may be important EV cargo. They emphasized that further research is needed and that it is important for researchers to consider age when using EVs as diagnostic or prognostic markers of disease. 

Click here to read the full editorial paper, published by Aging.

WATCH: MORE AGING VIDEOS ON LABTUBE

Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

2021 Ride for Roswell

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Aging Is Easily Treatable

In 2018, Dr. Mikhail Blagosklonny wrote a thought provoking theory article, entitled: “Disease or not, aging is easily treatable.”

Figure 1. Relationship between aging and diseases. When growth is completed, growth-promoting pathways increase cellular and systemic functions and thus drive aging. This is a pre-pre-disease stage, slowly progressing to a pre-disease stage. Eventually, alterations reach clinical disease definition, associated with organ damage, loss of functions (functional decline), rapid deterioration and death.
Figure 1. Relationship between aging and diseases. When growth is completed, growth-promoting pathways increase cellular and systemic functions and thus drive aging. This is a pre-pre-disease stage, slowly progressing to a pre-disease stage. Eventually, alterations reach clinical disease definition, associated with organ damage, loss of functions (functional decline), rapid deterioration and death.

The Top-Performer series highlights papers published by Aging that have generated a high Altmetric attention score. Altmetric scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

Read Aging’s Top 100 Altmetric papers.

Listen to an audio version of this article

Would re-classifying aging as an official disease help fuel the anti-aging drug industry? While many sufficient arguments can place aging in this category, Dr. Mikhail Blagosklonny—Editor-in-Chief at AgingOncotargetOncoscienceand Cell Cycle, and adjunct faculty member at the Roswell Park Comprehensive Cancer Center—believes that classifying aging as a disease is unnecessary and counterproductive.

“It is commonly argued that aging should be defined as a disease so as to accelerate development of anti-aging therapies. This attitude is self-defeating because it allows us to postpone development of anti-aging therapies until aging is pronounced a disease by regulatory bodies, which will not happen soon.”

In 2018, Dr. Blagosklonny wrote a theory article that was published in Aging’s Volume 10, Issue 11, and entitled, “Disease or not, aging is easily treatable.” To date, this top-performing paper has generated an Altmetric Attention score of 54.

“HEALTHY” AGING

In this article, Dr. Blagosklonny emphasizes his theory that human aging is the quasi-programmed continuation of growth and development. He explains that progressive aging later in life results in aberrant systematic hyperfunction, which leads to disease and, eventually, death. 

“Aging is a normal continuation of the normal developmental program, so it is NOT a program but a purposeless, unintended quasi-program [1016].”

Beginning after the growth process, Dr. Blagosklonny segments the aging process into four stages: pre-pre-diseasepre-diseaseclinical disease, and death (see Figure 1). In the early stages of aging, the unseen asymptomatic abnormalities which arise have not yet reached the currently agreed upon clinical definitions of disease. Dr. Blagosklonny explains that “healthy” aging can be interchangeable with “pre-pre-disease” and “pre-disease.”

“‘Healthy’ aging has been called subclinical aging [33], slow aging [18,34] or decelerated aging [35], during which diseases are at the pre-disease or even pre-pre-disease stage.”

TREATING AGING

“Aging is easily treatable.”

Dr. Blagosklonny justifies this instinctually debatable claim simply by pointing out the ways in which humans are already defying aging. Calorie restriction, intermittent fasting, and the ketogenic diet have all been proven to slow aging and extend healthy lifespan. Certain nutrients, conventional drugs, and pharmacological therapies which have shown anti-aging properties include metformin, aspirin, statins, beta-blockers, ACE inhibitors, Angiotensin II receptor blockers (ARB), and (the anti-aging therapy Dr. Blagosklonny is most intrigued by) rapamycin, and other rapalogs. 

“Rapamycin (Rapamune/Sirolimus), an allosteric inhibitor of mTOR complex 1 [63,66], is a natural rapalog as well as the most potent and best studied rapalog.”

Dr. Blagosklonny chronicles numerous studies over the years verifying rapamycin’s life- and health-extending effects in microorganisms, mice, humans, (non-human) primates, and even canines. Read more about the origin and applications of rapamycin.

PREVENTATIVE MEDICINE IS ANTI-AGING

“Gerontologists think of metformin as an anti-aging drug [121130], and metformin can be combined with rapamycin [131].”

In addition to the use of rapamycin and other anti-aging drugs, current preventative medicine strategies can be seen as anti-aging therapies, and vice versa. Dr. Blagosklonny discusses examples of preventative medicine and anti-aging therapy. In one example, patients who present with pre-diabetic symptoms may be treated with metformin to decrease insulin-resistance in advance, in order to prevent diabetes in the future. This is an example of preventative medicine as an anti-aging therapy.

“Physicians generally do not think of metformin as an anti-aging drug, simply because it is expected that life will be extended, if diseases are prevented.”

CONCLUSION

“Aging does not need to be defined as a disease to be treated.”

In conclusion, Dr. Blagosklonny proposes that “aging can be treated as a pre-disease to prevent its progression to diseases.” He suggests that, to preventatively combat disease brought on by aging, rapamycin and conventional life-extending drugs can be combined with “modestly low-calorie/carbohydrates diet, physical exercise, and stress avoidance.”

Click here to read the full theory article, published by Aging.

YOU MAY ALSO LIKE: MORE AGING VIDEOS ON LABTUBE

Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.


For media inquiries, please contact media@impactjournals.com.

Deep Learning Technology Consolidates Wearable Sensor Data

Smart watch / Smartphone

The Top-Performer series highlights papers published by Aging that have generated a high Altmetric attention score. Altmetric scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

Read Aging’s Top 100 Altmetric papers.

Listen to an audio version of this article

Wearable sensors (smartwatches, smartphones, and other devices) allow users to monitor some biomarkers of their own health with mobile biofeedback technology. In 2019, one-in-five adults in the United States reported regularly using a wearable fitness tracker or smartwatch. Since the COVID-19 pandemic, mobile downloads of health and home fitness apps have increased by 46%—in addition to a boom in wearable sensor use.

“Wearable device motion data have already been used for monitoring acute illnesses including detection of early signs of the outbreak of influenza-like illnesses [28] and COVID-19 [3034].” 

Large quantities of these data are being collected consistently from individual users. This potentially useful information is also being collected from large populations of people living in different countries, working in different occupations, with unique health statuses, and across multiple environmental seasons and stages of life. Wearable sensor data provides an opportunity to conduct large-scale studies that could lead to new global discoveries in aging and disease research.

“In fact, only mobile technology can support large-scale studies involving monitoring of early signs of a disease or measuring recovery rates, all requiring sampling more often than once per week.”

However, there are a number of different manufacturers of wearable sensors, smartwatches, and mobile devices. In addition to the inevitable inaccuracies, such as missing data, outliers, and even seasonal variation of physical activity, there are also varying measurements between devices of different manufacturers. These inaccuracies and variations create inconsistencies when comparing large-scale data from wearable sensors.

“We applied deep learning technology to systematically address these challenges.”

In 2021, researchers from Singapore’s Gero AI and Russia’s Moscow Institute of Physics and Technology authored a paper, published in Aging’s Volume 13, Issue 6, and entitled, “Deep longitudinal phenotyping of wearable sensor data reveals independent markers of longevity, stress, and resilience.” To date, this top-performing research paper has generated an Altmetric attention score of 43

The Study

“We trained and characterized a simple model that learns physical activity patterns from wearable devices, which are directly associated with morbidity risks on the population level.”

Three wearable sensor manufacturers were assessed in this study: UK Biobank, NHANES, and Healthkit. Researchers collected wearable sensor data for physical activity (steps per minute) from 103,830 users over the course of one week and, among 2,599 users, up to two years of data were collected. The team trained and validated a deep learning neural network technology—the GeroSense Biological Age Acceleration (BAA) system—to extract health-associated features from the physical activity recordings.  

“GeroSense BAA model employs additional neural network components to address this domain shift problem to ensure learning device-independent representations of the input signal.”

Conclusion

“We demonstrate that deep neural networks trained to predict morbidity risk from wearable sensor data can provide a high-quality and cheap alternative for BAA determination.”

The researchers explained that the application and wide deployment of their GeroSense BAA system may provide the means to accurately monitor stress and resilience in response to environmental conditions and interventions among people in different populations, countries, and socio-economic groups. 

“We hope that future developments will lead to further applications of AI in geroscience research, public health, and policy decision-making.”

Click here to read the full research paper, published by Aging.

YOU MAY ALSO LIKE: MORE AGING VIDEOS ON LABTUBE

Aging is an open-access journal that publishes high-quality research papers bi-monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our communities from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact media@impactjournals.com.

Trending With Impact: When Aging Switches On Alzheimer’s

In a trending Aging editorial paper, researchers explain that switches in the aging process may be a window of opportunity for patients with Alzheimer’s disease and potential epigenetic treatments.

Figure 1. The EORS downward spiral of aging and Alzheimer’s (Epigenetic Oxidative Redox Shift) [2].
Figure 1. The EORS downward spiral of aging and Alzheimer’s (Epigenetic Oxidative Redox Shift) [2].

The Trending with Impact series highlights Aging publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

Listen to an audio version of this article

Alzheimer’s disease (AD) develops at different times for different people due to known and unknown variables. AD and aging share a number of features in common, such as oxidative stress, mitochondrial impairment, and bioenergetic and metabolic shifts. Aging is an unmistakable risk factor for Alzheimer’s disease, but what causes aging to switch it on? Do these “switches” present opportunities for intervention?

In 2021, researchers from the University of California and the University of South Carolina wrote an editorial article about the onset of AD—propagated by switches that take place during the aging process. Their trending paper, published in Aging’s Volume 13, Issue 10, was entitled: “When aging switches on Alzheimer’s.”

“[…] the complex mechanisms of switching on so many AD pathologies remain underexplored.”

Oxidative Shifts

“Age-related redox stress, often measured as oxidative stress in aging and AD launches a global switch in the epigenetic landscape, widely affecting methylation, histone modification, and noncoding RNA regulation [5], to further drive downstream metabolic and energetic shifts.”

The authors begin this editorial paper by prefacing readers with the epigenetic oxidative redox shift theory of aging. They explain that the sedentary lifestyle often accompanied by old age resets epigenetic marks to prepare for low mitochondrial capacity and minimal energy production. In order to maintain this setting (resting redox energy levels), the body switches to require more oxygen and energy when performing physical activities and increases the conversion of glucose to lactose (the Warburg Effect). In turn, these metabolic shifts (now enforced by the epigenome) reinforce sedentary behavior—forming a vicious cycle.

“Our environment, lifestyle, stress, physical activity, and habits all modulate epigenetic control of gene expression for continuous environmental tracking.”

Conclusion

Oxidative shifts alter the activity of numerous redox-sensitive transcription factors, enzymes, and signaling proteins. The researchers explain that these oxidative switches taking place in patients with Alzheimer’s disease are potential targets for epigenetic treatments.

“While studies on these ‘switches’ enable elucidation of the underlying mechanisms for when aging switches on Alzheimer’s degeneration, more importantly, these ‘switches’ of redox, epigenetics and neuroinflammation encourage early interventions to decelerate AD pathology and retain functional memory.”

Click here to read the full paper, published by Aging.

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Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

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Trending with Impact: Aging and Lung Function Decline

Is there an association between biomarkers of aging and lung function? Researchers conducted a study which aimed to find out.

Human Respiratory System Lungs Anatomy

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By 2050, the United States Census Bureau estimates that 83.7 million people aged 65 years and older will be living in the U.S.—a number that will nearly double the 2012 estimated population. As the scale of the elderly population magnifies, additional aging research will continue to be increasingly relevant. 

“According to the American Lung Association, the lung matures by age 20-25 years, and its function declines gradually after the age of 35 [30].”

Among the elderly population, lung function has been found to vary, even between those who have never smoked, are the same height, and of the same chronological age. This has led researchers to wonder if lung function decline is part of the underlying biological aging processes. No published studies had investigated the associations between epigenetic aging biomarkers and lung function, until 2020.

In 2020, a team of researchers—from Harvard T.H. Chan School of Public HealthIcahn School of Medicine at Mount SinaiNorthwestern University Feinberg School of MedicineVA Boston Healthcare SystemBoston University School of Medicine, and Columbia University—aimed to begin answering this question. The researchers conducted a study with participants from the longitudinal Normative Aging Study (1963 – present) to determine whether or not there is an association between seven biomarkers of aging (BoA) and three measures of lung function. Their paper was published by Aging and entitled: “Biomarkers of aging and lung function in the normative aging study.”

“In this present study, we hypothesized that some of these BoA are associated with lower lung function.”

The Study

From 1961 to 1970, healthy U.S. males between the ages of 21 and 81 enrolled in the ongoing Veterans Affairs Normative Aging Study. One of the objectives of the study is to characterize the biomedical and psychosocial parameters of normal aging (distinct from the development of disease). There are a total of 2,280 participants in the Normative Aging Study (NAS). In the current Aging study, researchers included 696 elderly men from the NAS.

“The present study included 696 elderly men with 1,070 visits during years of 1999-2013.”

In search of associations between biomarkers of aging and lung function, the researchers first collected the study participants’ personal characteristics, including age, smoking history, height, weight, BMI, education, blood work, and other measures. They then analyzed lung function using three tests: forced expiratory volume in one second (FEV1), forced expiratory volume in one second / forced vital capacity (FEV1/FVC), and maximum mid-expiratory flow (MMEF).

Next, the team analyzed the participants’ epigenetic biomarkers of age; including GrimAgeAccel, PhenoAgeAccel, intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), and Zhang’s DNAmRiskScore; as well as non-epigenetic biomarkers of age, including telomere length and mitochondrial DNA copy number (mtDNA-CN). They then assessed for associations between these biomarkers and the three measures of lung function.

Conclusion

“In this longitudinal cohort of 696 elderly males, we found that GrimAgeAccel and Zhang’s DNAmRiskScore were associated with lower lung function, including FEV1, FEV1/FVC, and MMEF.”

The researchers found that the GrimAgeAccel and Zhang’s DNAmRiskScore were both associated with lower lung function in all three measures of lung function. They found no correlation between non-epigenetic aging biomarkers and lung function, but the researchers mention several limitations of their study. Their results suggest that epigenomic variation could help illuminate the pathogenesis of the reduced lung function that comes with age.

“Epigenetic mechanisms such as DNAm may provide further explanation for decreases in lung function as individual age.”

Click here to read the full paper, published by Aging.

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Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

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Can a Daily Dose of Electricity Improve Aging?

Researchers from the University of Leeds and the University of Glasgow conducted a 2019 study on the effects of transcutaneous vagal nerve stimulation (tVNS) among participants 55 years of age and older.

Medical illustration of vagus nerve with brain, lungs, heart, stomach and digestive tract.
Medical illustration of vagus nerve with brain, lungs, heart, stomach and digestive tract.

The Top-Performer series highlights papers published by Aging that have generated a high Altmetric attention score. Altmetric scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

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Among the cranial nerves, the vagus nerve has the largest distribution in the body. Extending from the brain to the abdomen, its name is derived from the Latin word vagari—which means “to wander.” This wandering nerve serves as part of the involuntary, or autonomic, nervous system. The vagus nerve is responsible for a number of important autonomic bodily functions, including lung function, heart rate, inflammation, brain/gut communication, mood, and even the consolidation of memories. 

Human aging is accompanied by progressive autonomic changes, including increases in sympathetic nervous activity (“fight or flight” responses) and decreases in parasympathetic nervous activity (“rest and digest” responses). These changes can have considerable effects on heart function, emotion, mood, gut function, and overall quality of life, and can often lead to an increase in medication consumption with age. 

TRANSCUTANEOUS VAGAL NERVE STIMULATION (TVNS)

In efforts to boost parasympathetic activity and decrease sympathetic activity, interventions such as vagus nerve stimulation (VNS) and transcutaneous vagal nerve stimulation (tVNS) have been developed. VNS is a highly invasive intervention, which involves surgically implanting an electrode around the cervical vagus nerve and a generator unit in the thoracic wall. Researchers have found that the non-invasive tVNS therapy (an electrical pulse focused on the tragus of the outer ear) is a safer and simpler intervention. Positive effects on autonomic function have been reported in non-patient groups treated with tVNS.

“tVNS is a simple, non-invasive and inexpensive therapy that involves stimulating the auricular branch of the vagus nerve (ABVN) at outer parts of the ear, conferring autonomic benefits in healthy volunteers [10].”

Previous research has shown that tVNS significantly reduces sympathetic nerve activity in healthy participants and boosts measures of parasympathetic activity. However, there are few studies available which detail the effects of tVNS in healthy older participants. 

“Despite this evidence, there is little work examining the autonomic implications of administering tVNS in healthy older individuals who are undergoing age-associated shifts towards sympathetic prevalence.”

THE STUDY

In 2019, researchers from the United Kingdom’s University of Leeds and University of Glasgow reported on the results of the effects of tVNS among participants 55 years of age and older in three studies. Their paper was published in Aging’s Volume 11, Issue 14, and entitled: “Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.” To date, this research paper has received an impressive Altmetric Attention score of 350.

In the first study, the researchers observed the effects of acute, single-session tVNS on cardiovascular autonomic function compared with the effects of sham (ear lobe/placebo) stimulation among 14 healthy participants 55 years of age and older. They collected baseline values and measured heart rate variability (HVR) and baroreflex sensitivity. 

“Since not all participants responded to tVNS, we examined if it was possible to identify potential tVNS responders from baseline parameters.”

In the second study, the researchers explored the effects of acute, single-session tVNS on autonomic function in the same age group and expanded the sample to 51 participants. The third study examined 26 participants in the same age group when administered tVNS once per day, for 15-minutes, over the course of two weeks. The researchers reported the impacts of daily tVNS in measures of autonomic function, health-related quality of life (QoL), mood, and sleep.

“Transcutaneous vagal nerve stimulation (tVNS) acutely administered to the tragus in healthy volunteers aged ≥ 55 years was associated with improvements in spontaneous cardiac baroreflex sensitivity and HRV.”

CONCLUSION

“For the first time, we have shown that age-related autonomic, QoL, mood and sleep changes may be improved with tVNS administered every day for two weeks.”

Although the researchers note that there are opportunities for improvement in this study design and further research is needed, participants reported improved sleep, depression, tension, vigor, and mood disturbance after two weeks of daily tVNS.

“These findings therefore suggest that daily tVNS may be an effective means of improving aspects of everyday life in this age group.” 

Click here to read the full research paper, published by Aging.

Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our communities from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.


For media inquiries, please contact media@impactjournals.com.

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