Counting the Calories: The Role of Specific Nutrients in Extension of Life Span by Food Restriction

Piper, Matthew D.W.; Mair, William; Partridge, Linda

doi:10.1093/gerona/60.5.549

Cited by 73 publications

(61 citation statements)

References 79 publications

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“…These surfaces show a remarkably consistent pattern, across the three insect species studied, of life span increasing as P:C ratios decreased and as caloric intake decreased. These studies, in conjunction with others Piper et al 2005;Ja et al 2009), demonstrate that nutrients, rather than calories, are responsible for life span extension via DR, at least for Drosophila, field cricket, and Q-flies.…”

Section: Introductionsupporting

confidence: 57%

Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios

Fanson

Taylor

2011

AGE

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Dietary restriction extends life span across a vast diversity of taxa, but significant challenges remain in elucidating the underlying mechanisms. Distinguishing between caloric and nutrient effects is an essential step. Recent studies with Drosophila and tephritid fruit flies have reported increased life span as dietary yeastto-sugar ratios decreased and these effects have been attributed to changes in protein-to-carbohydrate (P:C) ratios of the diets rather than calories. However, yeast is a complex mix of macronutrients and micronutrients, and hence changes in yeast content of the diet necessarily alters other nutrients in lockstep. To explicitly test whether studies using yeast are justified in attributing results to diet protein content rather than correlated nutrients, we developed a chemically defined diet allowing manipulation of just the ratio of protein (free amino acids) to carbohydrate (sucrose) levels of diets while holding other nutrients constant. Mated, female Queensland fruit flies (Q-flies) were fed 1 of 18 diets varying in P:C ratios and diet concentration. Diet consumption, egg production, and life span were recorded for each fly. In close concordance with recent studies using yeast diets, flies had increased life span as P:C ratios decreased, and caloric restriction did not extend life span. Similarly, egg production was maximized on high P:C ratios, but lifetime egg production was maximized on intermediate P:C ratios, indicating a life history trade-off between life span and egg production rate. Finally, Q-flies adjusted their diet intake in response to P:C ratios and diet concentration. Our results substantiate recent claims that P:C ratios significantly modulate life span in flies.

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Section: Introductionsupporting

confidence: 57%

Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios

Fanson

Taylor

2011

AGE

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“…In rats or mice, reduction of dietary methionine levels results in a significant life span extension, comparable to that of CR (Orentreich et al 1993;Miller et al 2005). In flies, limitation of yeast extract, the dietary source of amino acids, provides a greater longevity enhancement than reduction of sucrose (Piper et al 2005). Mutation of INDY, which encodes a carboxylate nutrient transporter localized to the gut and fat body of flies, increases life span (Rogina et al 2000;Inoue et al 2002;Knauf et al 2002;Marden et al 2003).…”

Section: Tor Activity Determines Life Span In Response To Amino Acidsmentioning

confidence: 99%

Extension of chronological life span in yeast by decreased TOR pathway signaling

Powers¹,

Kaeberlein²,

Caldwell³

et al. 2006

Genes Dev.

867

751

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Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time cells in a stationary phase culture remain viable, has been proposed as a model for the aging of post-mitotic tissues in mammals. We developed a high-throughput assay to determine CLS for ∼4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction. In support of this possibility, removal of either asparagine or glutamate from the media significantly increased stationary phase survival. Pharmacological inhibition of TOR signaling by methionine sulfoximine or rapamycin also increased CLS. Decreased TOR activity also promoted increased accumulation of storage carbohydrates and enhanced stress resistance and nuclear relocalization of the stress-related transcription factor Msn2. We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes.[Keywords: Saccharomyces cerevisiae; TOR; aging; life span; nutrients; yeast] Supplemental material is available at http://www.genesdev.org.

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“…On one hand, only a few studies have investigated whether it is possible to mimic the CR mediated effect on lifespan by reducing only selected macronutrients, so the evidence available is limited. On the other hand, some studies point out that it might be not the amount of calories affecting health span, but rather the reduction of specific nutrients, as reviewed elsewhere (Fanson et al 2009, Mair et al 2005, Piper et al 2005a.…”

Section: Mitochondrial Hormesis and Lifespanmentioning

confidence: 99%

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

2014

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ᮀ Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful.

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Counting the Calories: The Role of Specific Nutrients in Extension of Life Span by Food Restriction

Cited by 73 publications

References 79 publications

Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios

Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios

Extension of chronological life span in yeast by decreased TOR pathway signaling

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

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