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"
    http://www.geron.org/images/fall2013ppar.pdf

    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
    http://www.nytimes.com/2013/12/01/opinion/sunday/on-dying-after-your-time.html?smid=fb-share

     
  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
    http://online.wsj.com/news/articles/SB20001424052970204190804580131951809022766

    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
    http://onlinelibrary.wiley.com/doi/10.1111/acel.12342/full

    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?
     

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