Over 80 'Wellderly' Research Reveals Some Unexpected Twists

Damian McNamara

March 05, 2017

LA JOLLA, California — Smoking rates and body mass index are higher than expected in the "wellderly" — a group of elderly Americans living past age 80 free of common chronic diseases — according to researchers from the Healthspan Project at the Scripps Translational Science Institute in La Jolla, California.

"Some tend to smoke more [than those in the general population], although their weights are lower," said Ali Torkamani, PhD, of Scripps Translational Science Institute.

"But if you look at the distribution of body mass index [BMI], they are not all thin," he reported here at the 10th Future of Genomic Medicine (FOGM) Conference.

Greater insight into what keeps the wellderly healthy, despite the presence of some genetic or lifestyle factors that tend to predispose others to considerable morbidity, is an ongoing aim of the Healthspan Project.

"It's about evaluating people who have genetic markers that should make them sick and, instead, they defy the odds," explained session moderator Kathy Hudson, PhD, former deputy director of science, outreach, and policy at the National Institutes of Health (NIH). A 90-year-old woman, for example, can test positive for a BRCA mutation, although she has never been symptomatic or diagnosed with breast cancer.

What makes the research interesting is that it looks at both positive and negative factors, Dr Hudson continued. "In addition to an absence of bad things, what are the positive things you might have — not just genetically, but also lifestyle and environment — that we can learn from?"

It's about evaluating people who have genetic markers that should make them sick and, instead, they defy the odds.

Previous research shows certain genetic allele frequencies are associated with longevity, such as FOXO3A, SIRT1, CETP, andTP53. In the current study, rs280229, a variant of FOXO3A, achieved borderline significance for longevity (P = .059). However, Dr Torkamani pointed out that longevity just reflects the number of years someone lives, whereas healthspan is how long a person lives in optimal health.

The researchers also looked at single gene (eg, BRCA) and polygenic disorders — gene combinations that increase disease risk — in their cohort.

In terms of single gene mutations associated with disease in the wellderly and general population, "there was no difference in rates of known pathogenic variants, which was surprising," said Dr Torkamani. "I thought we had a lot of false positives, but we then filtered for highly confident pathogenic variants, and still there was no difference."

In terms of polygenic mutations, which "are what most people are worried about, we found reduced risk for coronary artery disease and Alzheimer's disease, and no change in type 2 diabetes, stroke, and cancer, which is also pretty surprising," he said.

Healthy Behaviors Play a Part, But Not a Starring Role

Investigators also looked at healthy behaviors that could contribute to living free of common chronic conditions such as coronary artery disease or type 2 diabetes in the wellderly cohort.

More of the wellderly population exercised compared with the general population, 67% vs 44%, respectively; but surprisingly, 61% of men in the Healthspan wellderly cohort had smoked compared with 54% of men in the general population. For wellderly women, smoking rates were similar to the general population (42% vs 43).

The median body weight of wellderly women was lower than women in the general population (132 vs 160 pounds), as was the median weight of wellderly men (168 vs 190 pounds).

"There are some signals showing they have healthy behaviors overall, but it's not all behavior," said Dr Torkamani. "Some individuals are above a BMI of 30 kg/m2, but are still wellderly, and we also know that some nonobese, relatively healthy people in the United States still have worse health outcomes."

It's probably not just luck.

Some people may just be more fortunate to live to 80 years and beyond without any major chronic diseases, said Dr Torkamani.

To investigate this further, he and his team studied the wellderly's siblings. They found that although the siblings do not live significantly longer than most people, they do have a highly significant health benefit in middle age. And siblings likely share some advantageous factors with the wellderly, so "it's probably not just luck," said Dr Torkamani

Precision Medicine Initiative: Adding to the Evidence

Further insight into health and ageing will be provided by the NIH's Precision Medicine Initiative, said Dr Hudson.

"It's the most meaningful project I've ever worked on," said Eric Dishman, MD, PhD, director of the All of Us research program, which is part of the Initiative.

After 17 years at Intel, Dr Dishman is bringing the thinking behind platform development to the NIH. "It's a national resource, the largest biologic and data repository to drive advanced breakthroughs in science and precision medicine forward," he said.

Scripps Translational Science Institute is also participating in the program, which has ambitious plans to longitudinally follow the health of one million Americans, said Dr Hudson, and could help find answers to Dr Torkamani’s questions about why the wellderly live so well for so long.

Dr Torkamani is a minor shareholder of Human Longevity, Inc, which is not related to the Healthspan Project. Dr Hudson has reported no relevant financial relationships.

10th Future of Genomic Medicine (FOGM) Conference. Presented March 3, 2017.


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