What is the key to healthy aging? New gene study sheds light

A NEW study may bring us closer to unlocking the secret to healthy aging, after uncovering an array of genetic variants among healthy, elderly individuals that may protect against Alzheimer’s and heart disease. The findings come from the ongoing “Wellderly” study, in which researchers have so far applied whole genome sequencing to the DNA of more than 1,400 healthy individuals from the US aged 80-105 years.
Launched in 2007, the study aims to pinpoint certain genetic variants that may contribute to lifelong health. “This study is exciting because it is the first large one using genetic sequencing to focus on health,” says Michael Snyder, PhD, chairman of the Department of Genetics at Stanford University in California, who was not involved with the research.
“Most of the world’s scientists are studying disease, but what we really want to understand is what keeps us healthy. That is what the Wellderly study is all about.” To reach the new findings – published in the journal Cell – co-senior study author Dr. Eric Topol, director of the Scripps Translational Science Institute (STSI) in La Jolla, CA, and colleagues used the Complete Genomics sequencing platform to analyse the genomes of 600 Wellderly participants.
All subjects were free of cancer, stroke, Alzheimer’s disease, Parkinson’s disease, diabetes, heart attack and any other chronic disease or illness. Their genomes were compared with those of 1,507 adults who represented the general population and who were part of a study conducted by the Inova Translational Medicine Institute (ITMI) in Falls Church, VA.
After controlling for blood relatedness and ethnic differences among the participants, the researchers were left with 511 individuals from the Wellderly study and 686 people from the ITMI cohort for whom they conducted downstream DNA analyses. All in all, the researchers analysed 24,205,551 specific gene variants across both groups.
Compared with the ITMI cohort, participants from the Wellderly study had lower genetic risks for Alzheimer’s disease and coronary artery disease – the most common form of heart disease. However, the team identified no difference in genetic risks for cancer, stroke or type 2 diabetes between the two groups, suggesting that participants of the Wellderly study possess other genetic characteristics or protective behaviours that prevent them from developing these diseases.
“We didn’t find a silver bullet for healthy longevity,” notes study co-author Ali Torkamani, PhD, director of genome informatics at STSI. “Instead, we found weaker signals among common as well as rare variant sites, which collectively suggest that protection against cognitive decline contributes to healthy aging.” Interestingly, the researchers identified a number of very rare variants in the COL25A1 gene of 10 individuals who were part of the Wellderly study. Such variants were not found in the ITMI cohort.

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