Researchers here report on an interesting in vitro exercise in the comparative biology of aging. They took fibroblast cells from ten difference mammalian species with widely divergent life spans and chemically induced DNA damage in the cells. Modern DNA sequencing approaches allow an accurate measure of the amount of mutational damage produced by this chemical treatment, which in turn allows a comparison of the degree to which cells from different species can resist such damage via the operation of DNA repair systems. Long-lived species have more efficient DNA repair mechanisms, as determined by this approach.
We test the hypothesis that excess mutations induced in primary fibroblasts by a low dose of N-ethyl-N-nitrosourea (ENU) are inversely correlated with species-specific maximum life span. To measure excess mutations induced by ENU we treated primary cells of 10 mammalian species, greatly differing in life span. We treated all cells with a low dose, non-toxic dose of ENU (20 ug/ml). We then extracted DNA from all treated and untreated cells and quantified somatic mutation burden by single-molecule sequencing. We measured excessive mutations by calculating the increase in single nucleotide variants (ΔSNVs) and we analyzed this across species with linear regression.
The average values for ΔSNV were found to range from 0.773 in mice to 0.367 in whale, resulting in a modest inverse correlation with species-specific maximum life span (R^2 = 0.2067). We conclude that DNA repair accuracy, the main determinant of genome sequence integrity, modestly correlates with life span suggesting that longer lived species have better repair capacities compared to shorter-lived species, which is in keeping with genome instability being a primary hallmark of aging and highlights its important role for longevity.
