An ambitious plan to sequence 100 genes in 1,000 healthy old people could shed light on genetic variations that insulate some people from the ailments of aging, including heart disease, cancer, and diabetes, allowing them to live a healthy life into their eighties and beyond. Rather than focusing on genetic variations that increase risk for disease, scientists plan to focus on genes that have previously been linked to health and longevity.

In recent years, advances in genetic screening technologies have allowed scientists to start searching the genome for clues to healthy aging and a lengthy life span. That work has revealed that the genomes of healthy old people are not blemish free. "These people have genetic susceptibility markers for many serious diseases, including cardiovascular disease, stroke, and diabetes, but they don't get any of these diseases," says Eric Topol, a cardiologist and head of the Genomic Medicine Program at the Scripps Translational Science Institute, in La Jolla, CA, who is leading the project. "What is the explanation? What might account for their insulation from these diseases?"

To answer that question, researchers are collecting blood samples from 1,000 people age 80 or older who have never suffered any serious illnesses and do not take medication. They plan to sequence 100 genes, known from animal research and other studies to influence health and aging. "We are especially interested in major housekeeping, master-control genes like [those involved in] DNA repair or insulin growth factor-1," a protein hormone involved in cell growth, says Topol. Enzymes involved in DNA repair are of interest in longevity research because cells often accumulate mistakes in their DNA sequence with age, and defects in some mouse and human DNA repair genes trigger what looks like premature aging. The receptor for insulin growth factor-1 (IGF1) has been shown to affect aging in mice, nematodes, and flies.

Most previous studies have sequenced only a small number of genes or used gene microarrays, which can quickly detect common genetic variations throughout the genome. But recent research suggests that a number of rarer variations in different genes play a role in health and disease. Sequencing allows researchers to determine if healthy older people are more likely to carry variations that either make protective factors function more efficiently or hinder the activity of harmful factors.