Living Past 100 May Be In Your Genes

MedicalResearch.com Interview with: Thomas Perls, MD, MPH Professor Boston University School of MedicineMedicalResearch.com 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.

Medical Research: What are the main findings?

Dr. Perls:   In this study, we analyzed survival data of the families of 1,500 participants in the New England Centenarian Study, the largest study of centenarians and their family members in the world, based at Boston Medical Center. Among those families, we looked at more than 1,900 sibling relationships that contained at least one person reaching the age of 90. We found that for people who live to 90 years old, the chance of their siblings also reaching age 90 is relatively small – about 1.7 times greater than for the average person born around the same time. But for people who survive to age 95, the chance of a sibling living to the same age is 3.5 times greater – and for those who live to 100, the chance of a sibling reaching the same age grows to about nine times greater. At 105 years old, the chance that a sibling will attain the same age is 35 times greater than for people born around the same time. However, this does not mean there are many 105 year old siblings running around. Because getting to such an age is so incredibly rare, just 10 sibships out of a 100 that contain a 105 year old will have another sibling living to that age. We also noted that the relative risks are higher for people born before 1890 versus those born after and this makes sense given that there were major changes in the public health around this time with cleaner water supplies, better socioeconomic conditions and so on and therefore the mortality rate, particularly among infants was dramatically declining.

Medical Research: What should clinicians and patients take away from your report?

Dr. Perls:  These much higher relative chances of survival likely reflect different and more potent genetic contributions to the rarity of survival being studied, and strongly suggest that survival to age 90 and survival to age 105 are dramatically different phenotypes or traits, with very different underlying and respectively stronger genetic influences.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Perls:   Because genes play a much stronger differentiating role in living to 105-plus years, studies of such individuals are much more powerful in discovering longevity-related genes than studies of people in their 90s. Therefore my co-authors and I call for investigators who are studying the determinants of living to the oldest ages to be precise in describing the rarity or percentile of survival that study participants achieve.

Citation:

Paola Sebastiani, Lisa Nussbaum, Stacy L. Andersen, Mara J. Black, and Thomas T. Perls. Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of Precise Definitions of “Aging,” “Life Span,” and “Longevity”. J Gerontol A Biol Sci Med Sci, 2015 DOI: 10.1093/gerona/glv020

MedicalResearch.com Interview with: Thomas Perls, MD, MPH Professor (2015). Living Past 100 May Be In Your Genes