Dietary Protein, Metabolism, and Aging

Soultoukis, George A; Partridge, Linda

doi:10.1146/annurev-biochem-060815-014422

Cited by 127 publications

(92 citation statements)

References 149 publications

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“…However, quantifying a balanced diet is challenging given the large numbers of nutrients involved. Among the major macronutrients, the proportion of protein is especially important, since relatively high levels that are important to sustain early life fitness can also incur a heavy cost to lifespan (Le Couteur et al., 2016, Soultoukis and Partridge, 2016). Thus, establishing protein balance is critical for understanding how diets can be used to enhance lifelong health.…”

Section: Introductionmentioning

confidence: 99%

Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

et al. 2017

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SummaryBalancing the quantity and quality of dietary protein relative to other nutrients is a key determinant of evolutionary fitness. A theoretical framework for defining a balanced diet would both reduce the enormous workload to optimize diets empirically and represent a breakthrough toward tailoring diets to the needs of consumers. Here, we report a simple and powerful in silico technique that uses the genome information of an organism to define its dietary amino acid requirements. We show for the fruit fly Drosophila melanogaster that such “exome-matched” diets are more satiating, enhance growth, and increase reproduction relative to non-matched diets. Thus, early life fitness traits can be enhanced at low levels of dietary amino acids that do not impose a cost to lifespan. Exome matching also enhanced mouse growth, indicating that it can be applied to other organisms whose genome sequence is known.

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Section: Introductionmentioning

confidence: 99%

Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

et al. 2017

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“…Reprogramming, currently an experimental tool to study development and cellular differentiation, may provide additional insights into the mechanisms of aging. Proposed drivers of physiological aging include the accumulation of DNA damage, increased ROS production, telomere shortening, cellular senescence, and defects in nuclear envelope architecture (Bernardes de Jesus and Blasco, 2013; Guarente, 2008; Haigis and Sinclair, 2009; Kennedy and Lamming, 2016; Soultoukis and Partridge, 2016; Steffen and Dillin, 2016). Multiple studies using animal models have demonstrated that the manipulation of these aging drivers leads to the manifestation of molecular hallmarks of aging that are shared between premature aging models and physiological aging (García-Prat et al, 2016; Mitchell et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

Ocampo

Reddy

Martínez-Redondo

et al. 2016

Cell

640

654

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SUMMARY Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.

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“…For example, the general control nonderepressible 2 (GCN2) protein provides a conserved AA sensing mechanism that is independent of AA identity [11,41]. In Drosophila larvae, GCN2 signaling in a small subset of dopaminergic neurons is required for the avoidance of diets with unbalanced AA levels, a process that seems to be independent of TOR signaling [42].…”

Section: Amino Acids Affect Lifespan and Reproduction Via Nutrient Sementioning

confidence: 99%

“…By testing diets with different nutrient compositions ('nutritional geometry framework') [7], it was found that the ratio of proteins to carbohydrates (P:C ratio), not overall energetic content, affects lifespan and reproduction in Drosophila [8,9]. Today, there is growing evidence that especially dietary proteins play a major role in mediating the effects of DR [10,11] (but see [12]). Remarkably, beyond the effects of the proteins themselves, recent work suggests that the building blocks of proteins, that is, specific amino acids (AA), can profoundly impact lifespan and associated traits.…”

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confidence: 99%

Amino acid modulation of lifespan and reproduction in Drosophila

Hoedjes

Rodrigues

Flatt

2017

Current Opinion in Insect Science

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1Manipulating amino acid (AA) intake in Drosophila can profoundly affect lifespan and reproduction. Remarkably, AA manipulation can uncouple the commonly observed trade-off between these traits. This finding seems to challenge the idea that this trade-off is due to competitive resource allocation, but here we argue that this view might be too simplistic. We also discuss the mechanisms of the AA response, mediated by the IIS/TOR and GCN2 pathways. Elucidating how these pathways respond to specific AA will likely yield important insights into how AA modulate the reproduction-lifespan relationship. The Drosophila model offers powerful genetic tools, combined with options for precise diet manipulation, to address these fundamental questions. Introduction: dietary effects on lifespan and reproductionNutrition plays a primary role in shaping the physiology, life history and behavior of organisms, and nutritional interventions can have substantial health benefits [1]. Dietary restriction (DR), that is, the reduced intake of nutrients without malnutrition, has been the most widely studied nutritional intervention since the 1930s when it was first demonstrated that DR extends lifespan in rats. Since then, a large body of research has established positive effects of DR on longevity and age-related pathology in numerous organisms, ranging from yeast and worms to insects and mammals. At the same time, DR typically reduces reproductive output [2,3]. The fact that reduced food intake extends lifespan at the expense of reproduction makes the study of DR, and of dietary effects more generally, of key significance for our understanding of the commonly observed trade-off between reproduction and longevity [4,5].Originally, reduced intake of calories was thought to be responsible for the lifespan-extending effects of DR, but this view began to shift when studies in Drosophila showed that lifespan extension under DR does not depend on caloric restriction [5,6]. By testing diets with different nutrient compositions ('nutritional geometry framework') [7], it was found that the ratio of proteins to carbohydrates (P:C ratio), not overall energetic content, affects lifespan and reproduction in Drosophila [8,9]. Today, there is growing evidence that especially dietary proteins play a major role in mediating the effects of DR [10,11] (but see [12]). Remarkably, beyond the effects of the proteins themselves, recent work suggests that the building blocks of proteins, that is, specific amino acids (AA), can profoundly impact lifespan and associated traits. For example, in both flies and mice, restriction of dietary methionine can extend lifespan to the same extent as DR [13][14][15][16].Here, we give a brief review of how AA modulate lifespan and reproduction, and the trade-off between these traits. We also provide a short overview of the molecular mechanisms by which AA might control these two traits and their relationship. We focus on recent research in the Drosophila model, given that this system combines unrivaled genetic tools, a solid...

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Dietary Protein, Metabolism, and Aging

Cited by 127 publications

References 149 publications

Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

Amino acid modulation of lifespan and reproduction in Drosophila

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