Calorie Restriction— the SIR2 Connection

  title={Calorie Restriction— the SIR2 Connection},
  author={Leonard P Guarente and Fr{\'e}d{\'e}ric Picard},

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Calorie restriction increases life span: a molecular mechanism.

  • G. Wolf
  • Biology
    Nutrition reviews
  • 2006
Lowering of adiposity appears to be one mechanism whereby calorie restriction affects life span.

Perinatal Food Deprivation Modifies the Caloric Restriction Response in Adult Mice Through Sirt1

The results suggest that maternal gestational weight gain could be an important life history trait and could be used to predict features that improve the invasive capacity or adjustment to seasonal food scarcity of the offspring.

Resveratrol improves health and survival of mice on a high-calorie diet

It is shown that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice onA standard diet and significantly increases their survival and point to new approaches for treating obesity-related disorders and diseases of ageing.

Sirt1: Def-eating senescence?

Sirt1 thus connects moderate calorie intake to “healthspan,” and a decline of Sirt-centered protective circuits over time may explain the “catastrophic” nature of aging.

Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster

The data reveal that diet composition, alone and in combination with overall caloric intake, modulates lifespan, consumption, and fat deposition in flies, and they provide a useful foundation for dissecting the underlying genetic mechanisms that link specific nutrients with important aspects of general health and longevity.

Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan

It is shown that, in the most common experimental conditions, lifespan extension by DR is abolished by providing Drosophila with ad libitum water, without altering food intake, indicating that DR, as conventionally studied in flies, is fundamentally different from the phenomenon studied in mammals.

The Nutritional Geometry of Aging

It is shown how the development of state-space geometric models in nutrition has provided a new approach to separating the effects of calories and nutrients and it is argued that similar geometric analysis is required for mammalian model systems.

Effects of Physiologic, Metabolic and Molecular Adaptations to Calorie Restriction on Biomarkers of Longevity

Results suggest that increased reliance on fatty acid oxidation and reductions in IGF-1 signaling may be metabolic pathways that mediate the effects of CR on aging and longevity.

Sirtuin‐independent effects of nicotinamide on lifespan extension from calorie restriction in yeast

It is reported here that CR increases lifespan independently of all Sir2‐family proteins in yeast and that nicotinamide has sirtuin‐independent effects on lifespan extension by CR.



Sirtuin activators mimic caloric restriction and delay ageing in metazoans

It is shown that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity, indicating that STacs slow metazoan ageing by mechanisms that may be related to caloric restriction.

Calorie restriction extends yeast life span by lowering the level of NADH.

It is shown that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2, validating the model that NADh regulates yeast longevity in response to CR.

Sir2 mediates longevity in the fly through a pathway related to calorie restriction.

  • B. RoginaS. Helfand
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
It is demonstrated that an increase in Drosophila Sir2 (dSir2) extends life span, whereas a decrease in dSir2 blocks the life-span-extending effect of calorie reduction or rpd3 mutations, which leads to a genetic pathway by which calorie restriction extends life spans and provides a framework for genetic and pharmacological studies of life span extension in metazoans.

Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.

Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

It is found that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far and indicates that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.

Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

It is shown that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process that activates Sir2 to extend lifespan.

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae

It is concluded that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase

It is shown that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals, suggesting that CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells.

How does calorie restriction work?

A molecular model for how calorie restriction works that incorporates recent findings on the molecular basis for the slowing in aging is proposed and how CR extends the life span in Saccharomyces cerevisiae is discussed.

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

A reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.