Aging, Author Interviews, Exercise - Fitness, Heart Disease, JAMA / 07.09.2021 Interview with: Amanda Paluch, PhD Assistant Professor University of Massachusetts Amherst Department of Kinesiology Institute for Applied Life Sciences Life Science Laboratories Amherst, MA 01003 What is the background for this study? Response: We wanted to understand the association of total steps per day with premature mortality among middle-aged, Black and White women and men.  This study included 2110 adults; age 38-50 years old at the start of this study.  These adults wore a step counting device for one week and then followed for death from any cause over the next 10 years. (more…)
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020 Interview with: Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada What is the background for this study? What are the main findings? Response: A previous study published in 2011 by my collaborator, Dr. Michel Chretien at the IRCM, identified a rare mutation in the PCSK9, termed Q152H. Individuals harboring this mutation demonstrated dramatic reductions in their LDL cholesterol levels and had a significantly lower risk of CVD. Furthermore, individuals harboring the Q152H mutation showed increases in longevity with no evidence of other diseases such as liver disease, cancer and chronic kidney disease. This Q152H mutation was unique with only 4 families in Quebec shown to harbor this genetic variant. In terms of its effect on PCSK9 expression/activity, the mutation at Q152H was precisely at the cleavage site in PCSK9 necessary for its activation. As a result, the Q152H mutation fails to be cleaved and activated, thereby blocking its secretion into the circulation. This is why the Q152H mutation is considered a loss-of-function PCSK9 mutant. Given our lab's interest in endoplasmic reticulum (ER) stress and ER storage diseases, we began to collaborate with Drs. Chretien and Seidah at the IRCM to investigate whether this Q152H mutant, when overexpressed in liver cells, would cause ER stress and liver cell injury. This was based on the findings that the Q152H mutant does not undergo autocatalytic cleavage and its subsequent secretion from liver cells. It is well known in the literature that the accumulation of misfolded or inactive proteins in the ER gives rise to ER stress and cell injury/dysfunction. As a result, we initially showed to our surprise that overexpression of the Q152H mutant in liver cells failed to cause ER stress BUT increased the protein levels of several important ER chaperones, GRP78 and GRP94, known to PROTECT against liver cell injury/dysfunction. As part of our JCI study, we furthered these studies to examine the effect of the Q152H mutant when overexpressed in the livers of mice. This is where we demonstrated that the Q152H mutation showed protection against ER stress-induced liver injury/dysfunction. (more…)
Aging, Author Interviews, Geriatrics, Heart Disease, Lancet, Lipids / 11.11.2020 Interview with: Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark What is the background for this study? Response: Previous studies have yielded mixed results regarding the association between elevated cholesterol levels and increased risk of atherosclerotic cardiovascular disease in individuals above age 70 years; with some studies showing no association and others only minimal association. However, these previous studies were based on cohorts recruiting individuals decades ago where life-expectancy were shorter and where treatment of comorbidities were very different from today (more…)
Aging, Author Interviews, BMJ, Exercise - Fitness / 08.10.2020 Interview with: Ulrik Wisløff Professor and Head of CERG and K.G. Jebsen Centre for Exercise in Medicine of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences NTNU-Norwegian University of Science and Technology Trondheim, Norway What is the background for this study? Response: The Generation 100 study followed more than 1500 women and men in their 70s for five years. The aim was to find out if exercise gives older adults a longer and healthier life, and we also compare the effect of moderate and high-intensity exercise. What are the main findings? Response: Overall survival was high in all three groups, compared to what’s expected in this age group. There was a clear trend towards greater survival in the high-intensity compared to the moderate intensity exercise group. High-intensity interval training also had the greatest effect on cardiorespiratory fitness and health-related quality of life. (more…)
Aging, Author Interviews / 11.07.2020 Interview with: John Gerard Tower Professor of biological sciences University of Southern California What is the background for this study? Response: Mifepristone is a synthetic steroid drug that is used in humans for birth control and as a treatment for Cushing’s disease, and is currently in clinical trials as an anti-cancer treatment. We have previously shown that mifepristone dramatically increases the life span of mated female Drosophila flies. (more…)
Aging, Author Interviews, Genetic Research / 24.06.2020 Interview with: Andrea Bodnar, Ph.D., Science Director Gloucester Marine Genomics Institute (GMGI) What is the background for this study? How does gene expression differ in the red sea urchin from humans?  Why is this animal not susceptible to age-related deterioration? Response: The red sea urchin is one of the earth’s longest-lived animals, living for more than 100 years without showing signs of aging. These animals grow and reproduce throughout their lives and show no increase in mortality rate or incidence of disease with age. This includes no reported cases of neoplastic disease, like cancer. To begin to understand the cellular mechanisms underpinning this extraordinary life history this study investigated gene expression patterns in the tissues of young and old red sea urchins. (more…)
Aging, Author Interviews, Genetic Research, JAMA / 27.08.2018 Interview with: Yi Zeng, Ph.D.| Professor, Center for Study of Aging and Human Development and Geriatrics Division, School of Medicine, Duke University Professor, National School of Development, Chief Scientist of Raissun Institute for Advanced Studies, Peking University Distinguished Research Scholar, Max Planck Institute for Demographic Research Foreign member of the Royal Netherlands Academy of Arts and Science What is the background for this study? What are the main findings? Response: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized healthcare. (more…)
Aging, Author Interviews, Genetic Research / 15.08.2018 Interview with: Aladdin H. Shadyab, PhD  MS, MPH, CPH Department of Family Medicine and Public Health University of California, San Diego What is the background for this study? What are the main findings? Response: Previous studies have shown that offspring of long-lived parents are not only likely to live longer but to also avoid major chronic diseases (e.g., coronary heart disease), have fewer chronic disease risk factors, and to have better cognitive and physical function in late life. However, few studies have examined parental longevity in relation to an overall measure of successful aging that included reaching old age free of both major diseases and disabilities. The objective of our study was to determine if parental longevity predicted healthy aging, defined as survival to age 90 without any major age-related diseases (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. The participants of our study were from the Women's Health Initiative, a large, longitudinal study among postmenopausal women from the United States. We observed that women whose mothers survived to at least age 90 years were 25% more likely to achieve healthy aging. We also observed that women whose fathers only lived to age 90 did not have increased likelihood of healthy aging. However, women whose mother and father both lived to age 90 were the most likely to achieve healthy aging. (more…)
Author Interviews, Weight Research / 13.07.2018 Interview with: Jennifer L. Kuk, PhD Associate Professor York University School of Kinesiology and Health Science Toronto, Ontario What is the background for this study? What are the main findings? Response: Most of the literature on metabolic health obesity has shown that individuals with 'metabolically healthy obesity' are still at increased mortality risk. However, most of these studies have defined healthy as zero or one metabolic risk factor.  This is problematic as hypertension, diabetes or dyslipidemia alone increase your mortality risk and should preclude you from the 'healthy' group. We show that individuals with obesity and no other metabolic risk factors are no more likely to die than normal weight individuals with no metabolic risk factors.  (more…)
Aging, Author Interviews, Genetic Research / 09.07.2018 Interview with: “siblings” by Katina Rogers is licensed under CC BY 2.0Stacy L. Andersen, PhD Assistant Professor of Medicine Project Manager New England Centenarian Study Long Life Family Study Boston University School of Medicine Boston Medical Center Boston, MA 02118 What is the background for this study? Response: Exceptional longevity appears to run in families. Previous studies have found that people who have siblings who live into their 90s or who reach 100 years of age have a greater chance themselves of living longer than the general population. Yet it is supercentenarians, those who reach the age of 110 years, who represent the true extreme of the human lifespan.  We wanted to determine whether the parents and siblings of supercentenarians were more likely to reach very old ages than family members of younger centenarians. We collected family tree information for 29 participants of the New England Centenarian Study aged 110-119 years. Proof of age documents and familial reconstruction methods were used to validate ages and dates of birth and death of the supercentenarian as well as his or her parents and siblings. Mean age at death was compared to birth year and sex-specific US and Swedish cohort life table estimates conditional on survival to age 20 for siblings to omit deaths due to nonheritable factors such as infectious disease or accidents and survival to age 50 (the approximate age at which women are no longer able to reproduce) for parents.  (more…)
Author Interviews, Endocrinology, JAMA / 19.09.2017 Interview with: Arjola Bano, MD, MSc, DSc Researcher in the Departments of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam the Netherlands What is the background for this study? What are the main findings? Response: Thyroid function is clinically defined by the measurements of serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels. So far, abnormal TSH and FT4 levels as well as variations within the normal range have been linked to an increased risk of cardiovascular disease and death. However, it remains unclear whether there are differences in life span and years of life lived with and without cardiovascular disease, within the reference range of thyroid function. To investigate this, we performed a prospective study among 7785 middle-aged and elderly people with normal thyroid function. Participants were part of the Rotterdam Study, 65 years on average and 52% females. In our statistical analyses, we accounted for sociodemographic and cardiovascular risk factors. Over a median follow-up of 8.1 years, 789 incident cardiovascular deaths and 1357 deaths occurred. Analyses were performed separately among men and women. Our study found differences in life expectancy within the reference range of thyroid function. At the age of 50 years, people with low-normal thyroid function lived up to 3.5 years longer than those with high-normal thyroid function. Also, people with low-normal thyroid function lived a longer life without cardiovascular disease than those with high-normal thyroid function. (more…)
Author Interviews, Genetic Research, Nature / 29.07.2017 Interview with: Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics Assistant professor at the Institute of Social and Preventive Medicine What is the background for this study? What are the main findings? Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome. (more…)
Aging, Author Interviews, McGill, Nature / 29.06.2017 Interview with: Pr. Siegfried Hekimi PhD McGill University What is the background for this study? What are the main findings? Response: We analyzed data about the longest living individuals over the period of time during which the record can be trusted. We found that there was no detectable plateauing of the maximum possible lifespan. This is consistent with not clearly observed plateau in the currently increasing average lifespan as well. (more…)
Aging, Author Interviews, Social Issues / 25.12.2016 Interview with: Sonja Hilbrand MSc Department of Psychology University of Basel Basel, Switzerland. What is the background for this study? Response: Grandparenting is a topic of both great practical and theoretical interest. For instance, grandparents in industrialized societies invest substantial amounts of time and money in their grandchildren and there are many studies examining the potential benefits for these grandchildren. Other studies have focused on potentially negative effects on grandparental mortality associated with providing custudial care for grandchildren. In addition to previous research we wanted to ask whether there are tangible benefits to the donors (grandparents) of the resources. In other words, is caring a one-way street or not. In our study we examined whether moderate amounts of caregiving were associated with the longevity of older adults. For our analysis we used longitudinal data of over 500 German individuals aged between 70 and 103 years. (more…)
Aging, Author Interviews, Heart Disease, JACC / 17.08.2016 Interview with: Dr Janice Atkins Research Fellow Epidemiology and Public Health University of Exeter Medical School RD&E Hospital Wonford Barrack Road, Exeter What is the background for this study? What are the main findings? Response: We have previously shown that having longer-lived parents increases your likelihood of living longer, and family history of heart attacks is already used by physicians to identify patients at increased risk of disease. However, it has been unclear how the health advantages of having longer lived parents is transferred to their middle-aged offspring. Our study of nearly 200,000 UK volunteers aged 55-73 at baseline, and followed for 8 years using health records data, found that having longer-lived parents reduced the risk of morbidity and mortality in the participants. We found that for each parent that lived beyond 70 years of age the participants had 20% less chance of dying from heart disease. To illustrate this, in a group of 1,000 people whose father’s died at 70 and followed for 10 years, on average 50 would die from heart disease. When compared to a group whose father’s died at 80, on average only 40 would die from heart disease over the same 10-year period. Similar trends were seen in the mother’s. The relationship between parental age at death and survival and health in their offspring is complex, with many factors playing a role. Shared environment and lifestyle choices play a large role, including smoking habits, high alcohol consumption, low physical activity and obesity; but even accounting for these factors parents lifespan was still predictive in their offspring. The biggest genetics effects on lifespan in our studies affected the participant’s blood pressure, their cholesterol levels, their Body Mass Index, and their likelihood to be addicted to tobacco. These are all factors that affect risk of heart disease, so is consistent with the lower rates of heart disease in the offspring. (more…)
Author Interviews, Infections, PNAS / 27.07.2016 Interview with: Adam Hayward PhD Impact Research Fellow University of Stirling What is the background for this study? Response: Adult life expectancies in industrialized countries have increased dramatically in the last 150 years, even once we’ve accounted for the fact that previously common deaths in childhood and now very rare. One hypothesis seeking to explain this increase is that childhood infections cause chronic inflammation, which are then linked with heart disease and stroke in later life, reducing lifespan. Since such childhood infections were previously common but are now, thanks to vaccine and sanitation, much rarer, chronic inflammation should be lower and people should live longer and be less likely to die from early-onset heart disease. If this hypothesis is correct, we should see that higher exposure to infections in early life leads to increased adult mortality and deaths from heart disease and stroke. (more…)
Aging, Author Interviews / 19.06.2015 Interview with: Arlene Ash Ph.D., Professor David Hoaglin Ph.D., Professor and Aimee R. Kroll-Desrosiers, MS Department of Quantitative Health Sciences University of Massachusetts Medical School Worcester, MA Medical Research: What is the background for this study? What are the main findings? Response: The Long Life Family Study (LLFS) is an international collaborative investigation of the genetics and familial components of exceptional survival, longevity, and healthy aging. It has enrolled members of long-lived sibships, their offspring, and spouses of either group.  Medicare claims data is a unique, nationally representative source of data on all treated diseases for most Americans over the age of 65. Our main question was: Does membership in a long-lived family protect against disease? For each American LLFS participant who was at least age 65 in 2008 and alive in 2009, we selected four persons from the general Medicare population who matched the participant on age, sex, and ZIP code of residence. We then used 2008–2010 Beneficiary Annual Summary Files from the Centers for Medicare & Medicaid Services (CMS) to compare the prevalence of 17 conditions among 781 LLFS participants in Medicare with those of 3,227 non-LLFS matches.* Analyses accounted for nesting within LLFS families and adjusted for age, sex, race, and year. Among LLFS participants identified as members of a long-lived sibship, 7 of the 17 conditions were significantly less common than for similarly aged controls (Alzheimer’s, hip fracture, diabetes, depression, prostate cancer, heart failure and chronic kidney disease); in contrast, 4 (arthritis, cataract, osteoporosis and glaucoma) were significantly more common. Spouses, offspring and offspring spouses of these long-lived siblings share in significantly lower risk for Alzheimer’s, diabetes and heart failure. Several additional analyses found suggestive (although not statistically significant) evidence of lower disease prevalence in both genetically and maritally-related LLFS cohort members. (more…)
Aging, Author Interviews, Genetic Research / 28.03.2015 Interview with: Thomas Perls, MD, MPH Professor Boston University School of Interview with: Thomas Perls, MD, MPH Professor Boston University School of Medicine Medical Research: What is the background for this study? Dr. Perls:   For years now, Gerontology scholars continue to state that 25% of what they interchangeably call aging, longevity, life expectancy and life span is genetic and 75% is due to the environment and health-related behaviors. This assertion is based on Scandinavian twins reared apart, but the oldest participants in those studies lived to their 70s and 80s. Part of the problem here is the lack of consistency in what people mean by the terms Aging, Life Span and Longevity. In fact, the Seventh Day Adventists, who generally have a high prevalence of healthy behaviors (vegetarian, daily exercise, eat in moderation, abstain from tobacco and alcohol, and activities that help manage stress well) have an average live expectancy of approximately 88 years. Yet, 7th Day Adventists are ethnically and racially heterogeneous and thus it appears that those healthy behaviors explain the vast majority of the variation in how old these people live to be. This finding is consistent with the optimistic view of the twin studies, that much of living to one's 80's is in our hands. Living to only our 50s-70's is also in our hands (e.g. 75% behaviors) if we choose to smoke, eat red meat frequently, be obese, not exercise, be exposed to gun violence, have unsafe sex, do IV drugs, etc. So it is safe to say, in my opinion, that 75% of the variation in how old we live to be, is on average due to our behavior and exposure choices. The empowering and important point is that if we all lived like the Seventh Day Adventists, average life expectancy would increase almost 8 years and health costs would markedly decline because we would be getting to these older ages because we are healthier not because we are pouring more resources into more effectively treating diseases. The New England Centenarian Study, which I direct, and a number of other studies of nonagenarians (people in their 90s) have demonstrated via direct genetic studies as well as studies of family trees where at least some family members get to these very old ages, that with older and older ages of survival beyond age ~95 years, variations in genetic profiles explain a greater and greater proportion of the variation in how old people live to be at these ages. So much so that I believe the findings to date are consistent with the roles of genes and environment being reversed for survival to age 106+ years, that is, 75% genetics and 25% environment/behaviors. This supposition is based upon several observations: (1) as people reach the age of 105+ years, they become more and more alike in terms of what age-related diseases they get and when they get them. Consistent with Jim Fries; "Compression of Morbidity" hypothesis, people who survive to ages 110+ (called supercentenarians) and who therefore approximate the limit of human lifespan are on average disease and disability-free up until the last 5 or so years of their lives. This increasing homogeneity, especially compared to the increasing heterogeneity in the rates of aging and incidences of age-related diseases at younger percentiles or ages of survival, suggests underlying genetic similarities (similar genetic profiles) amongst groups of these supercentenarians; and (2) the New England Centenarian Study previously discovered genetic signatures (made up of longevity-associated variations of about 130 genes) that were associated with surviving to age 106+ years with 80% accuracy, but with only 60% accuracy for accurately picking out people living to ~100 years. This increasing accuracy with older and older ages also suggests a stronger and stronger genetic influence upon survival to these rarest percentiles of survival. With the above background, we set out in this study and subsequent paper, to (1) assess sibling relative risk using the largest-ever collection of validated pedigrees of centenarians, (2) to assess the risk of a sibling achieving the same age as their very old sibling (e.g. ages 95, 100, or 105+ years) relative to average people born around the same time, and (3) to look at how when a person was born (eg before or after 1890) made a difference in these relative risks. (more…)
Aging, Author Interviews, Brigham & Women's - Harvard, Nutrition, Weight Research / 28.02.2015

William Mair, Ph.D Assistant Professor Department of Genetics and Complex Diseases Harvard T. H Chan School of Public Health Boston, MA Interview with: William Mair, Ph.D Assistant Professor Department of Genetics and Complex Diseases Harvard T. H Chan School of Public Health Boston, MA 02115 MedicalResearch: What is the background for this study? What are the main findings? Dr. Mair: Dietary restriction, the reduction of food intake without malnutrition has been known for 80 years to prolong lifespan in organisms ranging from single celled yeast to non human primates, and early signs suggest improvement of metabolic parameters in patients undergoing clinical trials. However, negative side effects associated with low calorie intake remain, and compliance and lifestyle factors make it an unappealing therapeutic. Since calorie restriction (CR) can have remarkable protective effects against multiple age onset diseases in mouse models - ranging from cancer to neurodegeneration to metabolic disease - finding molecular mechanisms though which calorie restriction functions might provide novel therapeutic targets that promote healthy aging. Using a model system, the nematode worm C. elegans, we show that perception of energy intake in the nervous system may be as critical for the effects of low energy on aging as actual calorie intake itself. Animals expressing an active form of a protein called AMPK, which is a cellular energy sensor, were long lived despite eating normally but this longevity could be turned off or on by changes to a neurotransmitter in just a few neurons. This suggests that therapeutic targets that modulate the perception of energy status in the nervous system might provide novel ways to gain the benefit of calorie restriction and promote healthy aging. (more…)
AHRQ, Author Interviews, Education, NIH, Race/Ethnic Diversity / 13.02.2015 Interview with: Robert M. Kaplan Office of Behavioral and Social Sciences Research National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Years of formal education is one of the strongest correlates of life expectancy. The purpose of this study was to examine the relationship between educational attainment and life expectancy with adjustments for other social, behavioral, and biological factors. Using data from a large cohort of nearly 30,000 adults, we found that education was a very strong predictor of survival and that biological and behavioral factors only partially explained the relationship. (more…)
Aging, Author Interviews, Genetic Research / 26.08.2014

Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Interview with: Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. Medical Research: What are the main findings of the study? Dr. Serrano: We investigated the contribution of rare genetic variation to human exceptional longevity (EL, individuals with ≥100 years of age) by exome-sequencing long-lived siblings in three different families where exceptional longevity clustered. We found only one gene that harbored rare variants that was likely to contribute to human longevity across all three families and this gene was the Apolipoprotein B gene (APOB). We further found that the frequency of these rare APOB variants associated with familial exceptional longevity was greater in a cohort of 206 nonfamilial cases of exceptional longevity compared to the control population, though this association did not reach statistical significance. In addition, we found rare variants in many genes within individual families that are likely to contribute to human longevity given previous studies in animals. (more…)
Alcohol, Author Interviews, General Medicine, Karolinski Institute / 17.01.2014

Andrea Bellavia MSc Institute of Environmental Medicine, Karolinska Institutet Stockholm, Interview with: Andrea Bellavia MSc Institute of Environmental Medicine, Karolinska Institutet Stockholm, Sweden Dr. Montgomery: What are the main findings of the study? Answer: We evaluated for 15 years a cohort of Swedish men and women and observed, after taking into account various socio-demographic, dietary, and lifestyle factors, that a low daily consumption of alcoholic beverages is tied with longer survival. (more…)