Octogenarians, Nonagenarians, & Centenarians

Discussion in 'Men's Health Forum' started by cvictorg, Jul 1, 2010.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    "The Longevity Dividend: Geroscience Meets Geropolitics"

    Finding a way to slow the biological processes of aging will do more to extend the period of healthy life in humans than attacking individual diseases alone, according to some of the nation’s top gerontologists writing in the latest issue of Public Policy & Aging Report (PP&AR).

    The authors showcase work in the emerging interdisciplinary field of geroscience, which is based on the knowledge that aging itself is the major risk factor for most chronic diseases prevalent in the older population.

    The PP&AR contains seven articles that discuss the contemporary pursuit of scientific means to extend the period of healthy life by slowing aging in people — known as the Longevity Dividend Initiative — and some of the obstacles that stand in the way of what many consider to be one of the most exciting breakthroughs in the history of science and public health.
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    On Dying After Your Time

  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Elder abuse, including neglect, on the rise as world's population begins to age
    By 2050, seniors will outnumber children for first time in history. Cynthia Thoresen, of Australia, gives a glimpse into how an increasing number of elderly spend their golden years: neglected, injured and alone.
    Elder abuse, including neglect, on the rise as world's population begins to age - NY Daily News

  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    How We Die Now: “Death renders all equal,” wrote Claudian. How each one of us relates to death, however, is individual, and always changing — as we mature; as we contemplate life, and death, around us; and as society changes.

    In this special series in the National Post, we present stories and columns looking at the different ways we see, and prepare for, the Great Equalizer. http://news.nationalpost.com/2013/10/25/the-full-death-issue-how-we-die-now/
  5. BBC3

    BBC3 Member

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  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Cash TP, Pita G, Domínguez O, et al. Exome sequencing of three cases of familial exceptional longevity. Aging Cell. http://onlinelibrary.wiley.com/doi/10.1111/acel.12261/full

    Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan.

    In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function.

    Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Interestingly, APOB is a component of lipoprotein particles together with APOE, and variants in the genes encoding these two proteins have been previously associated with human longevity.

    Analysis of nonfamilial EL cases showed a trend, without reaching statistical significance, toward enrichment of APOB RFVs. We have also identified candidate longevity genes shared between two families (5–13) or within individual families (66–156 genes).

    Some of these genes have been previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52, RAD51, NCOR1, and ADCY5 genes.

    This work provides an initial catalog of genes that could contribute to exceptional familial longevity.
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Google's War Against Aging
    Secretive Calico Unit Joins AbbVie in Potential $1.5 Billion Drug Research Project

    Google Inc. GOOGL +0.61% 's secretive Calico LLC life-sciences company unveiled a potential $1.5 billion research partnership with drug maker AbbVie Inc., ABBV +0.05% marking the entrance of a potentially big player in developing treatments for age-related diseases. http://www.calicolabs.com/news/2014/09/03/

    Google has said little about Calico, in which it is the primary investor, since forming the company last year with former Genentech Inc. Chief Executive Arthur Levinson. On Wednesday, a Google spokesman declined to say how many employees Calico has or whether it had begun any other research projects.

    Under the new partnership, Calico and AbbVie will each invest up to $250 million, and potentially another $500 million each, to tackle conditions like cancer and neurodegenerative disorders. The companies said they would share costs and profits from the collaboration equally.

    Calico, run by Mr. Levinson and former Genentech colleague Hal Barron, will build a research-and-development center in the San Francisco Bay Area. It will oversee early drug development and the early stages of human clinical trials for drugs. AbbVie will help Calico identify, design and conduct early-stage research, and has the option to manage late-stage drug development and marketing of any drugs that pass through the early stages of trials.

    Calico is one of several Google efforts to move beyond its Internet search roots into other industries being changed by technology. The AbbVie deal suggests Google is willing to put serious resources behind the project.

    "It's a drop in the bucket for Google, but they are seeking big outcomes by dramatically extending human life," said Scott Strawn, an analyst at research firm IDC. "These types of partnerships will be core to making this happen."

    The drug industry has had a mixed record in its efforts to significantly improve treatment for neurodegenerative diseases such as Alzheimer's and Parkinson's. Several experimental treatments designed to halt or reverse the underlying progression of those diseases have failed in recent clinical trials, including bapineuzumab, an experimental Alzheimer's treatment co-developed by Johnson & Johnson JNJ +0.08% and Pfizer Inc. PFE -0.10%

    Big pharmaceutical companies like AbbVie typically team with biotech startups later in the drug-development cycle around a specific treatment that has shown promise in clinical trials. With Calico, AbbVie is investing at least $250 million in a project that is just getting started and will focus on early-stage drug research for at least a decade.

    "This is a big leap into the unknown for AbbVie. Google is used to leaping into the unknown but AbbVie is not," said Aubrey de Grey, chief scientific officer at SENS Research Foundation, a charity that develops therapies for reducing and reversing aging.

    Calico, or California Life Company, is one of several companies using cheaper technology to analyze genetic information in the hopes of creating treatments for age-related diseases. The general goal is to identify genetic mutations that may contribute to long life, or that make some people more prone to diseases.

    Human Longevity Inc., co-founded by genetics pioneer Craig Venter, is building a huge database of human genetic data to tackle age-related diseases including cancer, diabetes and obesity, heart and liver diseases, and dementia.

    Chinese genomics giant BGI and biopharmaceutical company H3 Biomedicine Inc. launched a partnership last year to find gene mutations that could be potential targets for cancer drugs.

    Google's own research lab, Google X, is working on a study called Baseline, which it hopes will build a genetic and molecular picture of a healthy human. Other medical researchers will then be able to use that information to create treatments to prolong life.

    Calico hasn't identified its specific areas of focus yet, but it has been hiring medical-research experts in the past year and recently launched a website. Google hasn't disclosed how much money it has invested in Calico.

    In a post on Google+, Mr. Levinson called the AbbVie partnership a "pivotal event" that will "turbocharge" the company's efforts to prolong human life.

    David Botstein, Cynthia Kenyon and Robert Cohen joined Calico in late 2013. Dr. Botstein has been a leading genetics researcher for more than 30 years, while Dr. Kenyon's research shows that aging is a regulated process controlled by genes, rather than something unpredictable. Dr. Cohen helped Genentech develop several of the company's groundbreaking cancer drugs.

    AbbVie sells the prostate cancer drug Lupron and the company's oncology group is involved in more than 55 active clinical trials and is investigating more than 15 different cancers and tumors.

    On Wednesday, AbbVie and Inifinity Pharmaceuticals Inc. launched a partnership to develop a cancer drug call duvelisib.

    In neuroscience, AbbVie sells Duodopa for Parkinson's disease outside the U.S., and has been developing a potential new treatment for multiple sclerosis.
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Ageing Research: Blood To Blood - By splicing animals together, scientists have shown that young blood rejuvenates old tissues. Now, they are testing whether it works for humans. http://www.nature.com/news/ageing-research-blood-to-blood-1.16762

    Parabiosis is a 150-year-old surgical technique that unites the vasculature of two living animals. (The word comes from the Greek para, meaning 'alongside', and bios, meaning 'life'.)

    It mimics natural instances of shared blood supply, such as in conjoined twins or animals that share a placenta in the womb.

    In the past few years, however, a small number of labs have revived parabiosis, especially in the field of ageing research.

    By joining the circulatory system of an old mouse to that of a young mouse, scientists have produced some remarkable results. In the heart, brain, muscles and almost every other tissue examined, the blood of young mice seems to bring new life to ageing organs, making old mice stronger, smarter and healthier. It even makes their fur shinier.

    Now these labs have begun to identify the components of young blood that are responsible for these changes. And last September, a clinical trial in California became the first to start testing the benefits of young blood in older people with Alzheimer's disease.
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  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Published on Apr 7, 2015

    Dan Buettner, the New York Times bestselling author of The Blue Zones, lays out a proven plan to maximize your health based on the practices of the world’s healthiest people. For the first time, Buettner reveals how to transform your health using smart eating and lifestyle habits gleaned from new research on the diets, eating habits, and lifestyle practices of the communities he’s identified as “Blue Zones”—those places with the world’s longest-lived, and thus healthiest, people.

    With this book’s audacious belief that the lifestyles of the world’s Blue Zones could be adapted and replicated in towns across North America, you’ll be inspired by the specific stories of the people, foods, and routines of our healthy elders; understand the role community, family, and naturally healthy habits can play to improve our diet and health; and learn the exact foods—including the 50 superfoods of longevity and dozens of recipes adapted for Western tastes and markets—that offer delicious ways to eat your way to optimum health.

    Filled with moving personal stories, delicious recipes, checklists, and useful tips that will transform any home into a miniature blue zone, The Blue Zones Solution is the ultimate blueprint for a healthy, happy life.
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Longevity and Skeletal Muscle Mass: The Role of IGF Signalling, the Sirtuins, Dietary Restriction and Protein Intake

    Advancing age is associated with a progressive loss of skeletal muscle (SkM) mass and function. Given the worldwide aging demographics, this is a major contributor to morbidity, escalating socio-economic costs and ultimately mortality.

    Previously, it has been established that a decrease in regenerative capacity in addition to SkM loss with age coincides with suppression of insulin/insulin-like growth factor signalling pathways.

    However, genetic or pharmacological modulations of these highly conserved pathways have been observed to significantly enhance life and healthspan in various species, including mammals.

    This therefore provides a controversial paradigm in which reduced regenerative capacity of skeletal muscle tissue with age potentially promotes longevity of the organism.

    This paradox will be assessed and considered in the light of the following:

    (i) the genetic knockout, overexpression and pharmacological models that induce lifespan extension (e.g. IRS-1/s6K KO, mTOR inhibition) versus the important role of these signalling pathways in SkM growth and adaptation;

    (ii) the role of the sirtuins (SIRTs) in longevity versus their emerging role in SkM regeneration and survival under catabolic stress;

    (iii) the role of dietary restriction and its impact on longevity versus skeletal muscle mass regulation;

    (iv) the crosstalk between cellular energy metabolism (AMPK/TSC2/SIRT1) and survival (FOXO) versus growth and repair of SkM (e.g. AMPK vs. mTOR); and

    (v) the impact of protein feeding in combination with dietary restriction will be discussed as a potential intervention to maintain SkM mass while increasing longevity and enabling healthy aging.
  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lv J, Qi L, Yu C, Yang L, Guo Y, et al. Consumption of spicy foods and total and cause specific mortality: population based cohort study. BMJ 2015. http://www.bmj.com/content/351/bmj.h3942

    Objective To examine the associations between the regular consumption of spicy foods and total and cause specific mortality.

    Design Population based prospective cohort study.

    Setting China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.

    Participants 199 293 men and 288 082 women aged 30 to 79 years at baseline after excluding participants with cancer, heart disease, and stroke at baseline.

    Main exposure measures Consumption frequency of spicy foods, self reported once at baseline.

    Main outcome measures Total and cause specific mortality.

    Results During 3 500 004 person years of follow-up between 2004 and 2013 (median 7.2 years), a total of 11 820 men and 8404 women died. Absolute mortality rates according to spicy food consumption categories were 6.1, 4.4, 4.3, and 5.8 deaths per 1000 person years for participants who ate spicy foods less than once a week, 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Spicy food consumption showed highly consistent inverse associations with total mortality among both men and women after adjustment for other known or potential risk factors. In the whole cohort, compared with those who ate spicy foods less than once a week, the adjusted hazard ratios for death were 0.90 (95% confidence interval 0.84 to 0.96), 0.86 (0.80 to 0.92), and 0.86 (0.82 to 0.90) for those who ate spicy food 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Compared with those who ate spicy foods less than once a week, those who consumed spicy foods 6 or 7 days a week showed a 14% relative risk reduction in total mortality. The inverse association between spicy food consumption and total mortality was stronger in those who did not consume alcohol than those who did (P=0.033 for interaction). Inverse associations were also observed for deaths due to cancer, ischemic heart diseases, and respiratory diseases.

    Conclusion In this large prospective study, the habitual consumption of spicy foods was inversely associated with total and certain cause specific mortality, independent of other risk factors of death.
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  12. BBC3

    BBC3 Member

    "TOO SPIECEY FOR YANKEE DOG....! Too Spicy..! You stay 2 star.."

  13. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Life Span Has Little to Do with Genes, Analysis of Large Ancestry Database Shows
    Life span has little to do with genes, analysis of ancestry database shows - STAT

    Millions of amateur genealogists assembling family trees on Ancestry.com probably figure they’re just finding lost relatives and assessing their genetic proximity to Prince Harry, but in fact they have unintentionally made a significant contribution to science. An analysis of 54 million of the website’s public family trees finds that the heritability of life span, a hot research topic for decades, is considerably less than widely thought.

    Scientists reported on Tuesday that genes accounted for well under 7 percent of people’s life span, versus the 20 to 30 percent of most previous estimates.

    That low heritability “implies that it would be harder” to affect life span through genetic tinkering or other life extension ideas, said computational geneticist J. Graham Ruby of Calico Life Sciences, lead author of the study published in the journal Genetics. Google founded Calico in 2013 to find ways to combat aging.

    [OA] Ruby JG, Wright KM, Rand KA, et al. Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating. Genetics 2018;210:1109. Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating

    Human life span is a phenotype that integrates many aspects of health and environment into a single ultimate quantity: the elapsed time between birth and death. Though it is widely believed that long life runs in families for genetic reasons, estimates of life span “heritability” are consistently low (∼15–30%). Here, we used pedigree data from Ancestry public trees, including hundreds of millions of historical persons, to estimate the heritability of human longevity. Although “nominal heritability” estimates based on correlations among genetic relatives agreed with prior literature, the majority of that correlation was also captured by correlations among nongenetic (in-law) relatives, suggestive of highly assortative mating around life span-influencing factors (genetic and/or environmental). We used structural equation modeling to account for assortative mating, and concluded that the true heritability of human longevity for birth cohorts across the 1800s and early 1900s was well below 10%, and that it has been generally overestimated due to the effect of assortative mating.
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  14. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] 10-Year Follow-Up of The Super-Seniors Study: Compression of Morbidity and Genetic Factors

    BACKGROUND: Super-Seniors are healthy, long-lived individuals who were recruited at age 85 years or older with no history of cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease. In a 10-year follow-up, we aimed to determine whether surviving Super-Seniors showed compression of morbidity, and to test whether the allele frequencies of longevity-associated variants in APOE and FOXO3 were more extreme in such long-term survivors.

    METHODS: Super-Seniors who survived and were contactable were re-interviewed 10 years after initial characterization. Health and lifestyle were characterized via questionnaire. Geriatric tests including the Timed Up and Go (TUG), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL) and the Mini-Mental State Exam (MMSE) were administered, and data were compared to results from on average 10 years earlier. As well, genotype and allele frequencies for SNPs rs7412 and rs429358 in APOE, and rs2802292 in FOXO3 were compared to the frequencies in the original collection of Super-Seniors and mid-life controls.

    RESULTS: Of the 480 Super-Seniors recruited from 2004 to 2007, 13 were alive, contactable, and consented to re-interview (mean age = 100.1 +/- 3.3). Eight of these 13 participants (62%) still met Super-Senior health criteria. Diseases that occurred in late life were cardiovascular (5 of 13; 38%) and lung disease (1 of 13; 8%).

    MMSE and IADL scores declined in the decade between interviews, and GDS and TUG scores increased. The surviving group of centenarians had a higher frequency of APOE and FOXO3 longevity-associated variants even when compared to the original long-lived Super-Senior cohort.

    CONCLUSIONS: Although physical and mental decline occurred in the decade between interviews, the majority of Super-Seniors re-interviewed still met the original health criteria. These observations are consistent with reports of compression of morbidity at extreme ages, particularly in centenarians.

    The increased frequency of longevity- associated variants in this small group of survivors is consistent with studies that reported genetics as a larger contributor to longevity in older age groups.

    Tindale LC, Salema D, Brooks-Wilson AR. 10-year follow-up of the Super-Seniors Study: compression of morbidity and genetic factors. BMC geriatrics 2019;19:58. 10-year follow-up of the Super-Seniors Study: compression of morbidity and genetic factors
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  15. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Are We Approaching a Biological Limit to Human Longevity?

    Until recently human longevity records continued to grow in history, with no indication of approaching a hypothetical longevity limit. Also, earlier studies found that age-specific death rates cease to increase at advanced ages (mortality plateau) suggesting the absence of fixed limit to longevity too.

    In this study we re-examine both claims with more recent and reliable data on supercentenarians (persons aged 110 years and over). We found that despite a dramatic historical increase in the number of supercentenarians, further growth of human longevity records in subsequent birth cohorts slowed down significantly and almost stopped for those born after 1879.

    We also found an exponential acceleration of age-specific death rates for persons older than 113 years in more recent data. Slowing down the historical progress in maximum reported age at death and accelerated growth of age-specific death rates after age 113 years in recent birth cohorts may indicate the need for more conservative estimates for future longevity records unless a scientific breakthrough in delaying aging would happen.

    The hypothesis of approaching a biological limit to human longevity has received some empirical support and it deserves further study and testing.

    Gavrilova NS, Gavrilov LA. Are We Approaching a Biological Limit to Human Longevity? The Journals of Gerontology: Series A 2019. Are We Approaching a Biological Limit to Human Longevity?

    Attached Files:

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  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Untangling the Genetics of Human Longevity—A Challenging Quest

    Human average life expectancy in developed countries has increased dramatically in the last century, a phenomenon which is potentially accompanied by a significant rise in multi-morbidity and frailty among older individuals. Nevertheless, some individuals appear someway resistant to causes of death, such as cancer and heart disease, compared with the rest of the population, and are able to reach very old ages in good clinical conditions, while others are not.

    Thus, during the last two decades we have witnessed an increase in the number of studies on biological and molecular factors associated with the variation in healthy aging and longevity. Several lines of evidence support the genetic basis of longevity: from the species-specific maximum lifespan to the genetically determined premature aging syndromes.

    Studies in human twins, that aimed to distinguish the genetic from the environmental component, highlighted a heritability of life span close to 25%. In centenarian’s families, the offspring of long-lived individuals not only exhibit a survival advantage compared to their peers, but also have a lower incidence of age-related diseases.

    On the other hand, population studies found that genetic factors influence longevity in age- and sex-specific ways, with a most pronounced effect at advanced age and possibly in men compared to women. All this evidence indicates that a genetic influence on longevity exists, laying the foundation for the search for the genetic components of extreme long life.

    Consequently, over the past three decades, there has been a surge in genetic research, due in part to advances in molecular technologies, starting as studies of single genetic variants in candidate genes and pathways, moving on to array-based genome-wide association studies (GWAS) and subsequently to next generation sequencing (NGS). However, despite a plethora of studies, only few variants (in the APOE, FOXO3A and 5q33.3 loci) have been successfully replicated in different ethnic groups and the emerging picture is complex. …

    Dato S, Soerensen M, Rose G. Untangling the Genetics of Human Longevity—A Challenging Quest. Genes. 2019; 10(8):585. Untangling the Genetics of Human Longevity—A Challenging Quest
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  17. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Study: many of the “oldest” people in the world may not be as old as we think
    Study: many of the "oldest" people in the world may not be as old as we think

    We’ve long been obsessed with the super-elderly. How do some people make it to 100 or even 110 years old? Why do some regions — say, Sardinia, Italy, or Okinawa, Japan —produce dozens of these “supercentenarians” while other regions produce none? Is it genetics? Diet? Environmental factors? Long walks at dawn?

    A new working paper released on bioRxiv, the open access site for prepublication biology papers, appears to have cleared up the mystery once and for all: It’s none of the above. Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans

    Instead, it looks like the majority of the supercentenarians (people who’ve reached the age of 110) in the United States are engaged in — intentional or unintentional — exaggeration.

    [OA] Newman SJ. Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans. bioRxiv 2019:704080. Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans

    The observation of individuals attaining remarkable ages, and their concentration into geographic sub-regions or ‘blue zones’, has generated considerable scientific interest. Proposed drivers of remarkable longevity include high vegetable intake, strong social connections, and genetic markers.

    Here, we reveal new predictors of remarkable longevity and ‘supercentenarian’ status. In the United States, supercentenarian status is predicted by the absence of vital registration. The state-specific introduction of birth certificates is associated with a 69-82% fall in the number of supercentenarian records.

    In Italy, which has more uniform vital registration, remarkable longevity is instead predicted by low per capita incomes and a short life expectancy. Finally, the designated ‘blue zones’ of Sardinia, Okinawa, and Ikaria corresponded to regions with low incomes, low literacy, high crime rate and short life expectancy relative to their national average.

    As such, relative poverty and short lifespan constitute unexpected predictors of centenarian and supercentenarian status, and support a primary role of fraud and error in generating remarkable human age records.
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    ApoE Genotype, Lipid Profile, Exercise, and the Associations With Cardiovascular Morbidity and 18-Year Mortality

    Studies of longevity examined apolipoprotein E (ApoE), a gene involved in lipoprotein metabolism, which interacts with susceptibility to age-related diseases, and with mortality. We evaluated the association of ApoE isoforms with cardiovascular disease (CVD) and all-cause mortality.

    A prospective cohort of 949 survivors of the Israel Study of Glucose Intolerance, Obesity, and Hypertension, examined during 1999–2004, mean age 72 years, was followed for mortality until 2017. Participants were interviewed for lifestyle habits and medical history. Anthropometrics and biochemical markers were taken. Logistic regression was used to assess CVD morbidity and Cox proportional hazard model for mortality.

    The most common genotype in the cohort was ApoE E3 (76.3%), with the other two almost equally distributed (ApoE E2 11.2% and ApoE E4 12.5%).

    In men only, ApoE E4 associated with CVD (adjusted odds ratio = 1.46, 95% confidence interval [CI] 0.76, 2.80) and with 18-year mortality (adjusted hazard ratio = 1.47, 95% CI 0.95, 2.26), adjusting for age, ethnicity, physical activity, hypertension, diabetes, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides and lipid-lowering medications. Low levels of HDL cholesterol, adjusted for ApoE and the above-mentioned variables, associated with higher prevalence of CVD (adjusted odds ratio = 1.35, 95% CI 1.00, 1.83) and all-cause mortality (adjusted hazard ratio = 1.42, 95% CI 1.14, 1.78).

    ApoE E3 and E2 conferred a lower 18-year mortality risk in the physically active individuals, compared to the sedentary (adjusted hazard ratio = 0.57, 95% CI 0.44, 0.74, and adjusted hazard ratio = 0.53, 95% CI 0.78, 1.02, respectively).

    In community-dwelling older adults, sociodemographic characteristics and physical activity, blood pressure and HDL-cholesterol levels, may outweigh the impact of ApoE polymorphisms on CVD morbidity and all-cause mortality.

    Dankner R, Ben Avraham S, Harats D, Chetrit A. ApoE Genotype, Lipid Profile, Exercise, and the Associations With Cardiovascular Morbidity and 18-Year Mortality. The Journals of Gerontology: Series A 2019. https://doi.org/10.1093/gerona/glz232
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    New Tests Use Epigenetics to Guess How Fast You're Aging
    New Tests Use Epigenetics to Guess How Fast You're Aging

    From the beginning of time, humankind has searched for the secret to a long life. Now science may have found an answer, in the form of molecular augury. The pattern of chemical chains that attach to the DNA in your cells—on-off switches known as epigenetic markers—can reveal how swiftly you are aging, and perhaps even how much longer you will live. While genetic testing might tell you where you came from, epigenetics promises a glimpse into the future. Now, a handful of companies are offering commercial blood or saliva tests based on the science of epigenetics—a chance to find out how old you truly are.

    DNA itself is fixed; the genes you’ve inherited will forever make you more or less prone to certain conditions. But your epigenetic patterns change based on what you eat, how much you sleep or exercise, and what substances you are exposed to—and ultimately influence your risk of developing chronic conditions such as heart disease or diabetes. They do so by altering gene activity, like a complex set of controls that turn genes up or down, on or off.

    Epigenetics plays a role throughout life, from embryo development to aging, and some epigenetic changes accumulate as the years pass in a way that literally inscribes your age upon your body. That process is influenced by your environment and the things you do or don’t do. If you adopt a new exercise regimen or are exposed to pollutants, your epigenetic patterns may change for the better or worse.

    In 2011, after analyzing hundreds of epigenetic markers, Steve Horvarth developed the first epigenetic “clock,” a new way to calibrate aging. It measures specific epigenetic patterns that are linked to aging and disease, and compares that result against what would normally be expected for someone of your age. You may look or feel younger than expected, but this clock puts a number on it and tells you whether you really are aging more slowly than most other people.

    That number, what’s sometimes called your biological age, might be older or younger than the years you count on each birthday. Fifty can be the new 40, or 50 can be more like 60.

    Horvath, a biostatistician at the University of California Los Angeles, wasn’t trying to create a scientific oracle. A test of cellular aging, he reasoned, would be a powerful tool for researchers trying to find ways to prolong life and health. He created the test by focusing on methylation and demethylation, processes that grow or shrink those chemical chains and thereby control the action of genes. His clock accurately predicted biological age when tested in groups of hundreds of people, giving researchers an efficient way to look for the longevity benefits of drugs or lifestyle changes.

    At first, he had trouble publishing his results. It seemed too good to be true that a simple blood test could accurately predict lifespan, says Horvath. But other studies backed up his findings. He has refined the test over the years, and says his lab’s newest test, dubbed GrimAge for the Grim Reaper, is the most accurate yet. (He developed GrimAge for for research, although some version of it could become publicly available in the future.)

    The science of an epigenetic clock is now well-established. (There are other clocks in addition to Horvath’s.) The commercial tests to predict your biological age are based on this science—but these proprietary products aren’t independently evaluated. For example, they might not be equally accurate for all ethnic or racial groups.

    Still, they can give you some interesting information. Spit into a tube or prick your finger to take a few drops of blood, and send the samples off along with $299 or $500 depending on the test. If you smoke or if you are obese, your epigenetic markers are likely to be biologically older. If you are fit and have a healthy diet, you may detect the benefits.

    What’s enticing about this is that if you then make efforts to reduce your biological age by changing your habits, the test might be able to give you a reality check, and tell you whether you are succeeding. Just be aware that tests from different companies will measure different sets of patterns, and the results may not match.

    Epigenetic tests don’t need to be approved by the Food and Drug Administration, and company disclaimers state that they don’t screen for or assess disease risk. But already, some life insurance companies have begun using the tests, along with the usual physical exams and family history, to predict your lifespan.

    Generally, though, these tests aren’t fortune tellers. You won’t learn exactly how long you have left to live. For one thing, random events—a serious infection, a car accident—play a huge role in lifespan. For another, the test was designed to apply to a population, rather than an individual. It’s one thing to say that a group of people who share a similar pattern of methylation changes will, on balance, live longer. It’s quite another to accurately forecast one specific individual’s lifespan. “It’s not the case we could nail down the date of death of an individual within plus or minus one year,” Horvath says.

    Nonetheless, Horvath took his own test when he was 51, to see what it would tell him about how fast he is aging. His biological age was 48.9. His identical twin took the test, and interestingly, his result was exactly the same: 48.9.

    That doesn’t exactly mean Horvath will live precisely two years longer than expected. It’s a kind of shorthand, a simple way to convey whether you’re aging more quickly or slowly than the average person.

    Morgan Levine, a gerontologist and biostatistician at Yale University, created DNAm PhenoAge when she previously worked in Horvath’s lab. Her test was designed to reflect the risk of major diseases as well as overall lifespan. Beginning in January, her newest epigenetic clock will be sold as a commercial test beginning in January for $500 from the company Elysium Health, where she is head of bioinformatics. It measures patterns at 150,000 DNA methylation sites, which she says enhances its predictive value.

    Levine views the test as a tool for personalized prevention, enabling people to see if their healthy lifestyle changes cause their epigenetic age to decline, making them biologically younger. “This is much more reflective of lifestyle and behavior” than a genetic test, says Levine. “People have much more power over this number.”

    Commercial epigenetic testing is in its infancy, so consumers should be wary if companies make claims about a specific disease risk or offer to precisely predict lifespan—or use the results to market other products, says Robert Green, a medical geneticist at Brigham and Women’s Hospital in Boston who has studied direct-to-consumer genetic testing. “They have to understand that there’s a difference between something that is provided by a consumer-facing company and something that is recommended with the full force of medical science behind it,” says Green, cofounder of Genome Medical, which provides an online consultation service for people who undergo genetic testing.

    If you learn from an epigenetic test that you should improve your diet, lose weight, stop smoking, exercise more, and get more sleep—well, that’s advice you knew before shelling out a few hundred bucks. Still, sometimes a test result—genetic or epigenetic—may be what motivates you to actually change your habits, Green says.

    At 34, Levine is conducting her own personal experiment. She took her test last year; it showed her biological age to be 2.5 years younger than her chronological age. Previously a vegetarian, runner, and equestrian, she has now gone vegan and switched her workouts to high-intensity training, which has been linked to anti-aging changes in muscle. She plans to re-test monthly to see if her new regimen slows her biological aging.

    Larry Jia, founder and CEO of Zymo Research and Epimorphy, has been selling an epigenetic test that is a modified version of Horvath’s clock to researchers and consumers since 2017. He also took the test himself—and discovered that he is biologically a half-year older than his chronological age, which is 61. He began prioritizing sleep and cutting back on his hours to reduce his work stress, but the number didn’t budge—maybe, he says, because he can’t eliminate the stress of running a company. “Sometimes there are things you can’t control,” he says.

    After conducting thousands of tests for customers, he observes some patterns. The rate of aging seems to accelerate in people with a higher body mass index and in current smokers—as well as in people who engage in excessive and intense exercise or who have stressful jobs, he says. But he hasn’t seen that either a meat-heavy or mostly plant-based diet makes a significant difference.

    Epigenetic testing may seem as harmless as tapping into a biological horoscope, but it does raise some darker questions. Bioethicist Charles Dupras and his colleagues at McGill University in Montreal examined genetic anti-discrimination laws and found most would not apply to epigenetics. That means people may not be protected from misuse of their profile, such as might happen if employers wanted to use disease risk or other markers in hiring decisions. Privacy policies might not treat epigenetics as sensitive personal data, he says: “It’s another layer of information about the lives of consumers that should be safeguarded.”

    For now, our ability to turn back aging is somewhat limited to the familiar advice we already know so well: eat well, exercise, don’t smoke. But researchers are already using the epigenetic clock to test an anti-aging cocktail and to look for an anti-aging diet. If a wellspring of youth exists, epigenetic tests may be the ultimate divining rod.
  20. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Is Targeting Aging the Future of Medicine? Researchers Make the Case
    Is Targeting Aging the Future of Medicine? Researchers Make the Case

    Human life expectancy worldwide rose dramatically over the past century, but people’s health spans — the period of life spent free from chronic, age-related disease or disability — have not increased accordingly.

    But in the latest issue of the journal Public Policy & Aging Report (PP&AR) from The Gerontological Society of America, experts demonstrate that through interventions that impact the aging process itself, rather than through a focus on individual diseases, the scientific community can achieve a greater impact on both life and health expectancies. https://academic.oup.com/ppar/issue/29/4

    Titled “Is Aging Still a Disease? Perspectives from Geroscience,” the journal highlights existing studies as well as recommended areas for further research.

    The contents of the new PP&AR:
    • “It is Time to Embrace 21st-Century Medicine,” by Matt Kaeberlein, PhD, FGSA
    • “The Longevity Dividend: A Brief Update,” by S. Jay Olshansky, PhD, FGSA
    • “Time for a New Strategy in the War on Alzheimer’s Disease,” by Matt Kaeberlein, PhD, FGSA
    • “Is Old Age or Aging a Disease, in a Literal or a Metaphorical Sense?” by Stephen B. Kritchevsky, PhD, FGSA
    • “Is Aging a Disease? A Geriatrician’s Perspective,” by Peter A. Boling, MD
    • “A Regulatory Pathway for Medicines That Target Aging,” by G. Alexander Fleming, MD, Jennifer H. Zhao, BA, Thomas C. Seoh, JD, and Nir Barzilai, MD
    • “International Investment in Geroscience,” by Sean X. Leng, MD, PhD, FGSA, and Brian K. Kennedy, PhD, FGSA