Dietary restriction feeding extends survival in a range of species but a detailed understanding of the underlying mechanism is lacking. There is interest therefore in identifying a more targeted approach to replicate this effect on survival. We report that in rats dietary supplementation with alpha-lipoic acid, has markedly differing effects on lifetime survival depending upon the dietary history of the animal. When animals are switched from DR feeding to ad libitum feeding with a diet supplemented with alpha-lipoic acid, the extended survival characteristic of DR feeding is maintained, even though the animals show accelerated growth. Conversely, switching from ad libitum feeding a diet supplemented with alpha-lipoic acid to DR feeding of the non-supplemented diet, blocks the normal effect of DR to extend survival, even after cessation of lipoic acid supplementation. Unlike the dynamic effect of switching between DR and ad libitum feeding with a non-supplemented diet where the subsequent survival trajectory is determined by the new feeding regime, lipoic acid fixes the survival trajectory to that established by the initial feeding regime. Ad libitum feeding a diet supplemented with lipoic acid can therefore act as mimetic of DR to extend survival.
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