Gene-by-environmental modulation of longevity and weight gain in the murine BXD family
Summary 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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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 25. Mai Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Roy, Suheeta [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/776559 |
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| 520 | |a Summary 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. | ||
| 700 | 1 | |a Sleiman, Maroun Bou |e verfasserin |4 aut | |
| 700 | 1 | |a Jha, Pooja |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Evan G. |e verfasserin |4 aut | |
| 700 | 1 | |a Ingels, Jesse F. |e verfasserin |4 aut | |
| 700 | 1 | |a Chapman, Casey J. |e verfasserin |4 aut | |
| 700 | 1 | |a McCarty, Melinda S. |e verfasserin |4 aut | |
| 700 | 1 | |a Hook, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wenyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jinsong |e verfasserin |4 aut | |
| 700 | 1 | |a Neuner, Sarah M. |e verfasserin |4 aut | |
| 700 | 1 | |a Wilmott, Lynda A. |e verfasserin |4 aut | |
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| 700 | 1 | |a Centeno, Arthur G. |e verfasserin |4 aut | |
| 700 | 1 | |a Mozhui, Khyobeni |e verfasserin |4 aut | |
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| 700 | 1 | |a Kaczorowski, Catherine C. |e verfasserin |4 aut | |
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