First hint that body’s ‘biological age’ can be reversed Source: Nature | By Alison Abbott Nature 573, 173 (2019) doi: 10.1038/d41586-019...
First hint that body’s ‘biological age’ can be reversed
Source: Nature | By Alison Abbott
Nature 573, 173 (2019)
doi: 10.1038/d41586-019-02638-w
In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age.
A small clinical study in California has suggested for the first time that it might be possible to reverse the body’s epigenetic clock, which measures a person’s biological age.
For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.
The results were a surprise even to the trial organizers — but researchers caution that the findings are preliminary because the trial was small and did not include a control arm.
“I’d expected to see slowing down of the clock, but not a reversal,” says geneticist Steve Horvath at the University of California, Los Angeles, who conducted the epigenetic analysis. “That felt kind of futuristic.” The findings were published on 5 September in Aging Cell1.
“It may be that there is an effect,” says cell biologist Wolfgang Wagner at the University of Aachen in Germany. “But the results are not rock solid because the study is very small and not well controlled.”
Marks of life
The epigenetic clock relies on the body’s epigenome, which comprises chemical modifications, such as methyl groups, that tag DNA. The pattern of these tags changes during the course of life, and tracks a person’s biological age, which can lag behind or exceed chronological age.
Scientists construct epigenetic clocks by selecting sets of DNA-methylation sites across the genome. In the past few years, Horvath — a pioneer in epigenetic-clock research — has developed some of the most accurate ones.
The latest trial was designed mainly to test whether growth hormone could be used safely in humans to restore tissue in the thymus gland. The gland, which is in the chest between the lungs and the breastbone, is crucial for efficient immune function. White blood cells are produced in bone marrow and then mature inside the thymus, where they become specialized T cells that help the body to fight infections and cancers. But the gland starts to shrink after puberty and increasingly becomes clogged with fat.
Evidence from animal and some human studies shows that growth hormone stimulates regeneration of the thymus. But this hormone can also promote diabetes, so the trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, in the treatment cocktail.
The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age. It was led by immunologist Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, and was approved by the US Food and Drug Administration in May 2015. It began a few months later at Stanford Medical Center in Palo Alto, California.
Fahy’s fascination with the thymus goes back to 1986, when he read a study in which scientists transplanted growth-hormone-secreting cells into rats, apparently rejuvenating their immune systems. He was surprised that no one seemed to have followed up on the result with a clinical trial. A decade later, at age 46, he treated himself for a month with growth hormone and DHEA, and found some regeneration of his own thymus.
the TRIIM trial, the scientists took blood samples from participants during the treatment period. Tests showed that blood-cell count was rejuvenated in each of the participants. The researchers also used magnetic resonance imaging (MRI) to determine the composition of the thymus at the start and end of the study. They found that in seven participants, accumulated fat had been replaced with regenerated thymus tissue.
Rewinding the clock
Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.
Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.
“Because we could follow the changes within each individual, and because the effect was so very strong in each of them, I am optimistic,” says Horvath.
Researchers are already testing metformin for its potential to protect against common age-related diseases, such as cancer and heart disease. Fahy says that the three drugs in the cocktail might contribute separately to the effect on biological ageing through unique mechanisms. Intervene Immune is planning a larger study that will include people of different age groups and ethnicities, and women.
Regenerating the thymus could be useful in people who have underactive immune systems, including older people, he says. Pneumonia and other infectious diseases are a major cause of death in people older than 70.
Cancer immunologist Sam Palmer at the Heriot-Watt University in Edinburgh says that it is exciting to see the expansion of immune cells in the blood. This “has huge implications not just for infectious disease but also for cancer and ageing in general”.
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028
Aging Cell 08 September 2019
https://doi.org/10.1111/acel.13028
Reversal of epigenetic aging and immunosenescent trends in humans
Gregory M. Fahy, et al.
Abstract
Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age-related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (-2.5-year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from -1.6 year/year from 0–9 month to -6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2-year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention...
For these reasons, we conducted what may be the first human clinical trial designed to reverse aspects of human aging, the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) trial, in 2015–2017. The purpose of the TRIIM trial was to investigate the possibility of using recombinant human growth hormone (rhGH) to prevent or reverse signs of immunosenescence in a population of 51- to 65-year-old putatively healthy men, which represents the age range that just precedes the collapse of the TCR repertoire. rhGH was used based on prior evidence that growth hormone (GH) has thymotrophic and immune reconstituting effects in animals (Kelley et al., 1986) and human HIV patients (Napolitano et al., 2008; Plana et al., 2011). Because GH-induced hyperinsulinemia (Marcus et al., 1990) is undesirable and might affect thymic regeneration and immunological reconstitution, we combined rhGH with both dehydroepiandrosterone (DHEA) and metformin in an attempt to limit the “diabetogenic” effect of GH (Fahy, 2003, 2010; Weiss, Villareal, Fontana, Han, & Holloszy, 2011). DHEA has many effects, in both men and women, that oppose deleterious effects of normal aging (Cappola et al., 2009; Forti et al., 2012; Shufelt et al., 2010; Weiss et al., 2011). Metformin is a powerful calorie restriction mimetic in aging mice (Dhahbi, Mote, Fahy, & Spindler, 2005) and has been proposed as a candidate for slowing aging in humans (Barzilai, Crandall, Kritchevsky, & Espeland, 2016). Neither DHEA (Riley, Fitzmaurice, & Regelson, 1990) nor metformin are known to have any thymotrophic effects of their own...
DISCUSSION
The TRIIM trial was designed to investigate the possibility of thymus regeneration and reversion of immunosenescent trends in healthy aging men while minimizing side effects and any possible risks. Our results support the feasibility of this goal but unexpectedly also bring to light robust evidence that regression of multiple aspects and biomarkers of aging is possible in man. These two observations may be related.
Thymus regeneration and reactivation by growth hormone administration have been established in aging rats and dogs by restoration of youthful thymic histology (Goff, Roth, Arp, & al., e., 1987; Kelley et al., 1986) and by reversal of age-related immune deficits (Kelley et al., 1986). In humans, the existence of surviving thymic tissue after the age of about 54, which is required for successful thymus regeneration in older individuals, has been questioned (Simanovsky, Hiller, Loubashevsky, & Rozovsky, 2012). Available reports indicating increased thymic CT density and immunological improvements induced by rhGH in HIV patients (Napolitano et al., 2008; Plana et al., 2011), whose thymi are physiologically unusual (McCune et al., 1998), are silent on whether regeneration was observed in individuals over the age of 50. The present study now establishes highly significant evidence of thymic regeneration in normal aging men accompanied by improvements in a variety of disease risk factors and age-related immunological parameters as well as significant correlations between TFFF and favorable changes in monocyte percentages and the LMR, independent of age up to the age of 65 at the onset of treatment. These observations are consistent with the known ability of growth hormone to stimulate hematopoiesis and thymic epithelial cell proliferation (Savino, 2007). Our finding of an increase in FGF-21 levels after 12 months of treatment suggests that thymic regeneration by the present treatment may be mediated in part by this cytokine (Youm, Horvath, Mangelsdorf, Kliewer, & Dixit, 2016), which we believe is a novel finding…
[OpDis Editor Note: The human body is capable of far more than we imagine or what is begin said by doctors and experts in the medical field. It’s often enough that disease including faster aging is caused by environmental factors like pesticides, GMO’s, EM radiation and radioactive isotopes, unhealthy toxic food (including animal products). The human body is capable of homeostasis, aka self-healing but only when there’s not too much stress on the body to interfere with this function.]
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Our mission at Operation Disclosure is to bring you important news events and raw intel from various sources focused on exposing the Deep State/Cabal and their downfall. We are also focused on disclosing our lost ancient origins and extraterrestrial contact.
Disclaimer: All articles, videos, and images posted on Operation Disclosure were submitted by readers and/or handpicked by the site itself for informational and/or entertainment purposes. All statements, claims, views and opinions that appear on this site are always presented as unverified and should be discerned by the reader. We do not endorse any opinions expressed on this website and we do not support, represent or guarantee the completeness, truthfulness, accuracy, or reliability of any content posted on this website.
Copyright © 2019 Operation Disclosure
Source: Nature | By Alison Abbott
Nature 573, 173 (2019)
doi: 10.1038/d41586-019-02638-w
In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age.
A small clinical study in California has suggested for the first time that it might be possible to reverse the body’s epigenetic clock, which measures a person’s biological age.
For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.
The results were a surprise even to the trial organizers — but researchers caution that the findings are preliminary because the trial was small and did not include a control arm.
“I’d expected to see slowing down of the clock, but not a reversal,” says geneticist Steve Horvath at the University of California, Los Angeles, who conducted the epigenetic analysis. “That felt kind of futuristic.” The findings were published on 5 September in Aging Cell1.
“It may be that there is an effect,” says cell biologist Wolfgang Wagner at the University of Aachen in Germany. “But the results are not rock solid because the study is very small and not well controlled.”
Marks of life
The epigenetic clock relies on the body’s epigenome, which comprises chemical modifications, such as methyl groups, that tag DNA. The pattern of these tags changes during the course of life, and tracks a person’s biological age, which can lag behind or exceed chronological age.
Scientists construct epigenetic clocks by selecting sets of DNA-methylation sites across the genome. In the past few years, Horvath — a pioneer in epigenetic-clock research — has developed some of the most accurate ones.
The latest trial was designed mainly to test whether growth hormone could be used safely in humans to restore tissue in the thymus gland. The gland, which is in the chest between the lungs and the breastbone, is crucial for efficient immune function. White blood cells are produced in bone marrow and then mature inside the thymus, where they become specialized T cells that help the body to fight infections and cancers. But the gland starts to shrink after puberty and increasingly becomes clogged with fat.
Evidence from animal and some human studies shows that growth hormone stimulates regeneration of the thymus. But this hormone can also promote diabetes, so the trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, in the treatment cocktail.
The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age. It was led by immunologist Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, and was approved by the US Food and Drug Administration in May 2015. It began a few months later at Stanford Medical Center in Palo Alto, California.
Fahy’s fascination with the thymus goes back to 1986, when he read a study in which scientists transplanted growth-hormone-secreting cells into rats, apparently rejuvenating their immune systems. He was surprised that no one seemed to have followed up on the result with a clinical trial. A decade later, at age 46, he treated himself for a month with growth hormone and DHEA, and found some regeneration of his own thymus.
the TRIIM trial, the scientists took blood samples from participants during the treatment period. Tests showed that blood-cell count was rejuvenated in each of the participants. The researchers also used magnetic resonance imaging (MRI) to determine the composition of the thymus at the start and end of the study. They found that in seven participants, accumulated fat had been replaced with regenerated thymus tissue.
Rewinding the clock
Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.
Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.
“Because we could follow the changes within each individual, and because the effect was so very strong in each of them, I am optimistic,” says Horvath.
Researchers are already testing metformin for its potential to protect against common age-related diseases, such as cancer and heart disease. Fahy says that the three drugs in the cocktail might contribute separately to the effect on biological ageing through unique mechanisms. Intervene Immune is planning a larger study that will include people of different age groups and ethnicities, and women.
Regenerating the thymus could be useful in people who have underactive immune systems, including older people, he says. Pneumonia and other infectious diseases are a major cause of death in people older than 70.
Cancer immunologist Sam Palmer at the Heriot-Watt University in Edinburgh says that it is exciting to see the expansion of immune cells in the blood. This “has huge implications not just for infectious disease but also for cancer and ageing in general”.
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028
Aging Cell 08 September 2019
https://doi.org/10.1111/acel.13028
Reversal of epigenetic aging and immunosenescent trends in humans
Gregory M. Fahy, et al.
Abstract
Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age-related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (-2.5-year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from -1.6 year/year from 0–9 month to -6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2-year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention...
For these reasons, we conducted what may be the first human clinical trial designed to reverse aspects of human aging, the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) trial, in 2015–2017. The purpose of the TRIIM trial was to investigate the possibility of using recombinant human growth hormone (rhGH) to prevent or reverse signs of immunosenescence in a population of 51- to 65-year-old putatively healthy men, which represents the age range that just precedes the collapse of the TCR repertoire. rhGH was used based on prior evidence that growth hormone (GH) has thymotrophic and immune reconstituting effects in animals (Kelley et al., 1986) and human HIV patients (Napolitano et al., 2008; Plana et al., 2011). Because GH-induced hyperinsulinemia (Marcus et al., 1990) is undesirable and might affect thymic regeneration and immunological reconstitution, we combined rhGH with both dehydroepiandrosterone (DHEA) and metformin in an attempt to limit the “diabetogenic” effect of GH (Fahy, 2003, 2010; Weiss, Villareal, Fontana, Han, & Holloszy, 2011). DHEA has many effects, in both men and women, that oppose deleterious effects of normal aging (Cappola et al., 2009; Forti et al., 2012; Shufelt et al., 2010; Weiss et al., 2011). Metformin is a powerful calorie restriction mimetic in aging mice (Dhahbi, Mote, Fahy, & Spindler, 2005) and has been proposed as a candidate for slowing aging in humans (Barzilai, Crandall, Kritchevsky, & Espeland, 2016). Neither DHEA (Riley, Fitzmaurice, & Regelson, 1990) nor metformin are known to have any thymotrophic effects of their own...
DISCUSSION
The TRIIM trial was designed to investigate the possibility of thymus regeneration and reversion of immunosenescent trends in healthy aging men while minimizing side effects and any possible risks. Our results support the feasibility of this goal but unexpectedly also bring to light robust evidence that regression of multiple aspects and biomarkers of aging is possible in man. These two observations may be related.
Thymus regeneration and reactivation by growth hormone administration have been established in aging rats and dogs by restoration of youthful thymic histology (Goff, Roth, Arp, & al., e., 1987; Kelley et al., 1986) and by reversal of age-related immune deficits (Kelley et al., 1986). In humans, the existence of surviving thymic tissue after the age of about 54, which is required for successful thymus regeneration in older individuals, has been questioned (Simanovsky, Hiller, Loubashevsky, & Rozovsky, 2012). Available reports indicating increased thymic CT density and immunological improvements induced by rhGH in HIV patients (Napolitano et al., 2008; Plana et al., 2011), whose thymi are physiologically unusual (McCune et al., 1998), are silent on whether regeneration was observed in individuals over the age of 50. The present study now establishes highly significant evidence of thymic regeneration in normal aging men accompanied by improvements in a variety of disease risk factors and age-related immunological parameters as well as significant correlations between TFFF and favorable changes in monocyte percentages and the LMR, independent of age up to the age of 65 at the onset of treatment. These observations are consistent with the known ability of growth hormone to stimulate hematopoiesis and thymic epithelial cell proliferation (Savino, 2007). Our finding of an increase in FGF-21 levels after 12 months of treatment suggests that thymic regeneration by the present treatment may be mediated in part by this cytokine (Youm, Horvath, Mangelsdorf, Kliewer, & Dixit, 2016), which we believe is a novel finding…
[OpDis Editor Note: The human body is capable of far more than we imagine or what is begin said by doctors and experts in the medical field. It’s often enough that disease including faster aging is caused by environmental factors like pesticides, GMO’s, EM radiation and radioactive isotopes, unhealthy toxic food (including animal products). The human body is capable of homeostasis, aka self-healing but only when there’s not too much stress on the body to interfere with this function.]
______________________________________________________
Guest Posting
If you wish to write and/or publish an article on Operation Disclosure all you need to do is send your entry to UniversalOm432Hz@gmail.com applying these following rules.
The subject of your email entry should be: "Entry Post | (Title of your post) | Operation Disclosure"
- Must be in text format
- Proper Grammar
- No foul language
- Your signature/name/username at the top
______________________________________________________
Newsletter
If you wish to receive the daily Operation Disclosure Newsletter, you can subscribe here.
______________________________________________________
Our mission at Operation Disclosure is to bring you important news events and raw intel from various sources focused on exposing the Deep State/Cabal and their downfall. We are also focused on disclosing our lost ancient origins and extraterrestrial contact.
Disclaimer: All articles, videos, and images posted on Operation Disclosure were submitted by readers and/or handpicked by the site itself for informational and/or entertainment purposes. All statements, claims, views and opinions that appear on this site are always presented as unverified and should be discerned by the reader. We do not endorse any opinions expressed on this website and we do not support, represent or guarantee the completeness, truthfulness, accuracy, or reliability of any content posted on this website.
Copyright © 2019 Operation Disclosure
