Abstract
SummaryDiet and environment profoundly modulate lifespan. We measured longevity as a function of diet and weight gain across a genetically diverse family of mice. We followed 1348 females from two parental strains—C57BL/6J and DBA/2J—and 146 cohorts of BXD isogenic progeny strains (n= 73) across their lifespan on a low fat chow diet (CD, 18% calories from fat) and on a high fat diet (HFD, 60% calories from fat). On average, HFD shortens lifespan by 85 days or 12%, roughly equivalent to an 8–10 year decrease in humans. However, strain variation in the response of diet on longevity is remarkably high, ranging from a longevity loss of 54% in BXD65 to a gain of 37% in BXD8. Baseline weights and early weight gain are both associated with a mean decrease in longevity of ∼4 days/g. By 500 days-of-age, cases fed HFD gained four times as much weight as control on average. However, strain-specific variation was substantial, thus weight gain did not correlate well with lifespan. In summary, high fat had a strong negative effect on longevity, but genetic interactions effects were even stronger. This highlights the unequivocal importance of genetic differences in making dietary recommendations.
Publisher
Cold Spring Harbor Laboratory
Cited by
6 articles.
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