Abstract
Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.
Highlights
Dietary restriction regimes extend lifespan in various animal models
Mean lifespan was prolonged by 102 days (AL: 806 days, every-other-day feeding (EOD): 908 days) and maximum lifespan, calculated based on the longest living 20%, was extended by 122 days (AL: 980 days, EOD: 1102 days) (Fig. 1e), which is within the range of lifespan extension observed in previous Dietary restriction (DR) studies[13]
A detailed pathological examination of dead mice revealed that most EOD and AL mice had died of neoplastic disorders (Fig. 1f), most notably hematological malignancies, known leading natural causes of death in both sexes of many inbred mouse strains, including C57BL/6J6, 14
Summary
We show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in everyother-day feeding mice than in controls. In order to systematically study EOD’s effects on aging and lifespan, we performed a large-scale analysis of >200 molecular, cellular, histopathological, and physiological parameters across >20 different tissues in mice subjected to EOD or AL access to food for much of their lifetime. In addition to the analyses of aging phenotypes, we determined EOD’s effects on lifespan and assessed causes of natural death in cohorts chronically subjected to EOD or AL
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