Ever since the 1950s, when DNA was confirmed as nature’s primary genetic material, scientists have theorized that aging is caused by the gradual accumulation of mutations in the DNA sequences of genes. But until now no one has been able to test this “somatic mutation theory of aging,” since mutations are random and fairly rare events.

Recently, two researchers in the laboratory of Einstein’s Jan Vijg, Ph.D., developed an assay that uses single-cell whole-genome sequencing to determine the number of mutations in cells from different organs and tissues. In a paper published October 27 in Science Advances, those same two researchers (Xiao Dong, Ph.D., and Lei Zhang, Ph.D., both now at the University of Minnesota) describe using their assay to measure the mutation burden induced by a given dose of a known mutagen (an agent that causes mutations) in human lung cells and in lung cells from different rodent species with greatly differing lifespans: from a mouse that lives only 3 years to a naked mole rat that lives for more than 30. Lung cells from humans and other long-lived species were better able than the short-lived species to minimize their mutation burden, probably because the long-lived species have superior DNA repair systems. The findings strongly support the somatic mutation theory of aging and suggest that strategies for slowing the accumulation of cell mutations could help people live longer.

Dr. Vijg, a co-senior author of the paper, is professor and chair of genetics, professor of ophthalmology & visual sciences, and Lola and Saul Kramer Chair in Molecular Genetics at Einstein. The rodent cells were provided by Vera Gorbunova, Ph.D., University of Rochester, a collaborator in this NIH-supported study.