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Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation.

Wang Y - Diabetes Metab J (2014)

Bottom Line: Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms.SIRT1 exerts protective effects against a number of age-associated disorders.A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.

ABSTRACT
Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.

No MeSH data available.


Related in: MedlinePlus

In response to different dietary intake, a number of nutrient sensing pathways are activated or inactivated to modulate the ageing process. IGF, insulin-like growth factor; SIRT1, Sir2-like protein 1; AMPK, AMP-activated protein kinase; mTOR/S6K, mammalian target of rapamycin/ribosomal protein S6 kinase; ROS, reactive oxygen species; AKT/PKB, AKT/protein kinase B.
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Figure 1: In response to different dietary intake, a number of nutrient sensing pathways are activated or inactivated to modulate the ageing process. IGF, insulin-like growth factor; SIRT1, Sir2-like protein 1; AMPK, AMP-activated protein kinase; mTOR/S6K, mammalian target of rapamycin/ribosomal protein S6 kinase; ROS, reactive oxygen species; AKT/PKB, AKT/protein kinase B.

Mentions: The biological basis of caloric restriction remains poorly understood. The involvement of a single gene and pathway has been investigated in non-mammalian systems [3]. For example, removal of ethanol and/or acetic acid extends the chronological longevity (the survival of a population of nondividing cells) of the model organism yeast, whereas their replicative lifespan (the number of daughter cells generated by a single mother cell) is more sensitive to glucose restriction [6]. Down-regulation of Sch9, a serine-threonine kinase that shares high sequence identity with the mammalian Akt/protein kinase B (PKB) and ribosomal protein S6 kinase (S6K), extends the chronological lifespan by up to 2-fold [7]. Reduction of the TOR complex 1 activity leads to an extension of yeast replicative lifespan that cannot be further promoted by caloric restriction [8]. In the fruit fly Drosophila, reduction of amino acid consumption, but not sugar intake, extends life span substantially with essential amino acids mediating most of the responses [9]. In mammals, although different nutrient contents are sensed by distinctive pathways; however, it is unlikely that one single pathway is responsible for the effect of caloric restriction. Restricted dietary intake triggers the inactivation or activation of a number of nutrient sensing pathways, including insulin-like growth factor (IGF)/insulin, mammalian target of rapamycin/S6K, and silent information regulator 2 (Sir2)-like protein 1 (SIRT1) signaling pathways. These pathways are also involved in the antiageing effects of a number of chemical compounds and drugs (Fig. 1).


Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation.

Wang Y - Diabetes Metab J (2014)

In response to different dietary intake, a number of nutrient sensing pathways are activated or inactivated to modulate the ageing process. IGF, insulin-like growth factor; SIRT1, Sir2-like protein 1; AMPK, AMP-activated protein kinase; mTOR/S6K, mammalian target of rapamycin/ribosomal protein S6 kinase; ROS, reactive oxygen species; AKT/PKB, AKT/protein kinase B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209345&req=5

Figure 1: In response to different dietary intake, a number of nutrient sensing pathways are activated or inactivated to modulate the ageing process. IGF, insulin-like growth factor; SIRT1, Sir2-like protein 1; AMPK, AMP-activated protein kinase; mTOR/S6K, mammalian target of rapamycin/ribosomal protein S6 kinase; ROS, reactive oxygen species; AKT/PKB, AKT/protein kinase B.
Mentions: The biological basis of caloric restriction remains poorly understood. The involvement of a single gene and pathway has been investigated in non-mammalian systems [3]. For example, removal of ethanol and/or acetic acid extends the chronological longevity (the survival of a population of nondividing cells) of the model organism yeast, whereas their replicative lifespan (the number of daughter cells generated by a single mother cell) is more sensitive to glucose restriction [6]. Down-regulation of Sch9, a serine-threonine kinase that shares high sequence identity with the mammalian Akt/protein kinase B (PKB) and ribosomal protein S6 kinase (S6K), extends the chronological lifespan by up to 2-fold [7]. Reduction of the TOR complex 1 activity leads to an extension of yeast replicative lifespan that cannot be further promoted by caloric restriction [8]. In the fruit fly Drosophila, reduction of amino acid consumption, but not sugar intake, extends life span substantially with essential amino acids mediating most of the responses [9]. In mammals, although different nutrient contents are sensed by distinctive pathways; however, it is unlikely that one single pathway is responsible for the effect of caloric restriction. Restricted dietary intake triggers the inactivation or activation of a number of nutrient sensing pathways, including insulin-like growth factor (IGF)/insulin, mammalian target of rapamycin/S6K, and silent information regulator 2 (Sir2)-like protein 1 (SIRT1) signaling pathways. These pathways are also involved in the antiageing effects of a number of chemical compounds and drugs (Fig. 1).

Bottom Line: Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms.SIRT1 exerts protective effects against a number of age-associated disorders.A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.

ABSTRACT
Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.

No MeSH data available.


Related in: MedlinePlus