Gene-by-environmental modulation of longevity and weight gain in the murine BXD family
Maroun Bou Sleiman,
Evan G. Williams,
Jesse F Ingels,
Casey J Chapman,
Melinda S McCarty,
Sarah M. Neuner,
Lynda A. Wilmott,
Thomas M Shapaker,
Arthur G. Centeno,
Megan K. Mulligan,
Catherine C. Kaczorowski,
Robert W. Read,
Richard A. Miller,
Robert W. Williams
Posted 19 Sep 2019
bioRxiv DOI: 10.1101/776559
Posted 19 Sep 2019
Diet 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.
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