Amino acid imbalance explains extension of lifespan by dietary restriction in Drosophila

By R. Grandison, M. Piper, Linda Partridge. Nature, 2009

774 citations recorded by the source corpus.

Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.

Subfields: Aging, Ecology, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/7ead190364d289bdb309c86b0b18a2f01cc5d2ee

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Citations in the corpus

Ancient Protostome Origin of Chemosensory Ionotropic Glutamate Receptors and the Evolution of Insect Taste and Olfaction (2010, background): “melanogaster, despite their vital importance for normal insect physiology and metabolism [50], but amino acids are chemosensory stimulants in other insects, lobsters and molluscs [51–53].”
mTOR: from growth signal integration to cancer, diabetes and ageing (2010, background): “melanogaster , supply of a single amino acid, Met, allows the maintenance of reproductive potency in the context of DR-induced lifespan extensio”
Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster (2010, background): “that reduced fecundity and longevity can be uncoupled (Grandison et al., 2009; Partridge et al., 2005).”
Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism (2013, background): “Moreover, restriction of dietary methionine can extend lifespan in fruit flies and rodents (Grandison et al., 2009; Orentreich et al., 1993).”
Fishing‐induced evolution of growth: concepts, mechanisms and the empirical evidence (2012, background): “Surplus resources are often termed ‘surplus energy’ (Ware 1975; Roff 1983) or ‘growth effort’ (Abrams & Rowe 1996); by referring to ‘resources’ we acknowledge that not only is the total energy important, but the nature of that energy (e.g. its nutrient composition) has consequences as well (e.g. Pul”
Extending life span by increasing oxidative stress. (2011, background): “hand, supplementation of essential amino acids, especially methionine, abolishes the life-span-extending effect of CR in flies [33].”
The nature of nutrition: a unifying framework (2011, background): “Grandison et al. (2009) have shown that, for flies at least, the answer is ‘no’.”
Autophagy and aging. (2011, background): “CR does not further increase life span when TOR signaling is already reduced in yeast, worms, or flies, suggesting that commonmechanismsmediate both of these anti-aging interventions (Grandison et al., 2009).”
SIRTUIN 1 AND SIRTUIN 3: PHYSIOLOGICAL MODULATORS OF METABOLISM (2012, background): “More recently, this concept has been challenged (211), and evidence points to the effect of specific amino acids in determining the effects of long-term calorie restriction on life span and fertility (118, 219).”
Benefits and costs of parental care (2012, background): “Finally, methionine stimulates fecundity (egg production) in female fruit flies, but only in a specific ratio with other essential amino acids (Grandison et al. 2009).”