Scripps researchers publish findings from Wellderly study in Cell
When asked whether he celebrated his recent 90th birthday, John Rawlings shook his head. “I’ll celebrate when I hit 100,” he responds with a smile. And by the look of it, he might very well reach that momentous milestone. At 90, Rawlings, who lives in San Diego, California, is the oldest member of his softball team. He plays three times a week and also works out at a gym – an exercise regime that puts most people a third his age to shame. But what’s his secret? How is he able to lead such an active lifestyle despite his advanced age?
Rawlings is one of approximately 1,400 individuals, between the ages of 80 and 105, participating in the Wellderly study, a clinical trial led by scientists at the Scripps Translational Science Institute (STSI). He belongs to a unique and enviable cohort of people who have lived into their ninth decade and beyond without developing any chronic illnesses. The study, launched in 2007, seeks to understand the genetic mechanisms that underpin their ability to avoid developing age-associated disease.
Chronic diseases, such as diabetes, heart disease, and hypertension, account for two-thirds of human deaths worldwide. According to the Centers of Disease Control and Prevention, they are the leading cause of death and disability in the United States, and account for more than 75% of health care costs.[1] While the links between chronic diseases and health risk behaviors, such as smoking, poor diet and lack of physical activity, have been firmly established, less attention has been paid to what mechanisms at the genetic level protect against age-associated illnesses.
The goal of the Wellderly study is to determine what is special about the genetics in this group of people and how these genetic characteristics contribute to healthy aging. By identifying the genetic components that protect the Wellderly from disease, scientists may be able to use this information to develop ways to prevent disease in the general population.
In a paper published in the scientific journal Cell, researchers at STSI have outlined initial findings from their analysis of the whole genome sequences of the Wellderly. The genomic data used for the analysis was collected over eight years from study participants across the country, and was made publicly available in the hope of spawning further research into late onset diseases and healthy aging. “Healthspan is woefully understudied,” says Dr. Eric Topol, Director of STSI and one of the study’s senior authors. “Much more work in large numbers of individuals across all populations is desperately needed.”
In order to identify genetic features of the Wellderly that may protect against age-associated disease, researchers at STSI performed both a common variant whole genome sequencing-based genome-wide association study, as well as a rare variant burden analysis. A genome-wide association study, or GWAS, allows researchers to examine common genetic variants to determine if any variant is associated with a particular trait, such as healthy aging. A rare variant burden analysis allows researchers to identify groups of rare variants impacting the same gene to determine whether any specific gene contains rare variants collectively associated with a particular trait. Results from these analyses, may allow scientists to identify particular genetic variants and further our understanding of genetic courses of disease-free healthy aging.
The results from the Wellderly genetic analyses implicate the preservation of cognitive function as a critical factor in healthy aging. “The health of the brain is a very important component of living to an advanced age,” says Dr. Ali Torkamani, Director of Genome Informatics at STSI and a senior author of the study. For example, the researchers found that APOE-ε4 allele was present in a substantially lower number of Wellderly, as compared to general population controls. This particular allele has previously been shown to be associated with longevity, but is also considered a ‘frailty’ allele for late onset disease. The STSI researchers also witnessed an overall decrease in genetic risk for Alzheimer’s and coronary artery disease among the Wellderly.
“We’re not immediately going to be able to translate these findings into better health for the general population. However, in the long term, identifying these variants that cause healthy aging will allow us to add to the body of knowledge that can eventually help all of us live to an advanced age, and be healthy,” Torkamani says.
The study concludes that healthy aging, also known as healthspan, is a separate but related phenotype to longevity (i.e., living a long life). Studying the genetics of healthy aging is a powerful way for identifying genetic mechanisms of resistance to age-associated disease.
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Read the full study in Cell.
Read the joint press release from Scripps Health and The Scripps Research Institute outlining the results of the Wellderly study.
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