CTSA Program-Supported Research Uncovers Genetic Components of Healthy Aging

Older adults often face aging-related ailments such as heart disease, dementia and high blood pressure, all of which can be costly and shorten lifespans. However, some people live long lives without encountering these common health problems. What sets apart healthy agers from their peers?

To find out, Scripps Translational Science Institute (STSI) researchers led efforts to sequence and compare the genomes of 511 healthy agers — whom they deemed the “Wellderly” — and a representative group of 686 older adults. The STSI scientists defined the Wellderly as those aged 80 and older who had no chronic diseases and were not taking medications for chronic illnesses.

Study results, published in Cell, reveal that the Wellderly had reduced genetic susceptibility to Alzheimer’s disease, suggesting that protection against cognitive decline is at least one genetic feature of healthy aging.

Ali Torkamani and Galina Erikson

Ali Torkamani, Ph.D. (left), and Galina Erikson, authors on the Wellderly study by Scripps Translational Science Institute. (Scripps Research Institute Photo)

“Teasing apart the genetics of natural disease resistance could help us identify therapeutic targets to help prevent or treat age-associated diseases,” said Ali Torkamani, Ph.D., assistant professor and director of drug discovery at STSI and senior author of the article.

Torkamani’s group found that the Wellderly had fewer genetic variants linked to Alzheimer’s and had a genetic modification that potentially helped protect them against this disease. This finding suggests that protection against cognitive decline could be at least one genetic feature of healthy aging.

The Wellderly also had decreased genetic risk for coronary artery disease and a marginal, statistically not significant, decrease in stroke risk, which might be more significant in a larger group of participants. The researchers are continuing to recruit additional Wellderly participants to validate their initial findings.

The STSI scientists say these findings represent only a fraction of the potential information that can be gleaned from the results, so they have publicly released the study’s genomic data to help promote additional discoveries by other investigators. This exemplifies one of NCATS’ key priorities: to foster collaboration and accelerate translation by publicly sharing data and resources.

STSI is funded in part through NCATS’ Clinical and Translational Science Awards (CTSA) Program. STSI houses an arsenal of facilities, expertise and services that are available to its investigators to accelerate clinical and translational research. The Wellderly researchers used several STSI resources, including clinical trial coordinators to recruit participants* and biostatisticians and computational biologists to analyze and interpret the genomic data. The team also used REDCap, a CTSA Program-wide software tool, to collect participant data.


*Inova Health Systems contributed DNA from the control group of older adults.


Posted August 2016