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Calorie restriction as an intervention in ageing.

López-Lluch G, Navas P - J. Physiol. (Lond.) (2016)

Bottom Line: CR produces a pleiotropic effect and improves multiple metabolic pathways, generating benefits to the whole organism.Finally, the anti-inflammatory effect of CR is an interesting emerging factor to be taken into consideration.In the present revision we focus on the general effect of CR and other mimetics in longevity, focusing especially on the cardiovascular system and skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto de Salud Carlos III, Carretera de Utrera km. 1, 41013, Sevilla, Spain.

No MeSH data available.


Related in: MedlinePlus

Complex interaction of proliferative and protective mechanisms in the CR prolongevity effect in organismsNearly all the organisms studied to date have shown similar mechanisms in response to CR. Basically, CR induces mechanisms involved in energy efficacy and inhibits mechanisms involved in less efficient energy consumption and proliferation. Thus, CR inhibits IGF‐I‐dependent signalling which activates TOR and protein synthesis and inhibits FoxO, blocking antioxidant expression and autophagy. On the other hand, the balance between AMP and ATP and NAD+ and NADH serves as a signal to activate AMPK and sirtuins, respectively. These nutrient sensors and regulators block the signal dependent on IGF‐I and TOR at the same time as they activate mechanisms to enhance more efficient energy production through oxidative metabolism and mechanisms to enhance cell protection through antioxidants and organelle turnover through autophagy. At the same time, CR, through sirtuins, can block inflammation mediators. This regulation occurs at different levels and many mediators can produce a redundant response such as autophagy activation by blocking TOR‐dependent FoxO inhibition or by inducing the activity of autophagy‐related (ATG) proteins.
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tjp6990-fig-0002: Complex interaction of proliferative and protective mechanisms in the CR prolongevity effect in organismsNearly all the organisms studied to date have shown similar mechanisms in response to CR. Basically, CR induces mechanisms involved in energy efficacy and inhibits mechanisms involved in less efficient energy consumption and proliferation. Thus, CR inhibits IGF‐I‐dependent signalling which activates TOR and protein synthesis and inhibits FoxO, blocking antioxidant expression and autophagy. On the other hand, the balance between AMP and ATP and NAD+ and NADH serves as a signal to activate AMPK and sirtuins, respectively. These nutrient sensors and regulators block the signal dependent on IGF‐I and TOR at the same time as they activate mechanisms to enhance more efficient energy production through oxidative metabolism and mechanisms to enhance cell protection through antioxidants and organelle turnover through autophagy. At the same time, CR, through sirtuins, can block inflammation mediators. This regulation occurs at different levels and many mediators can produce a redundant response such as autophagy activation by blocking TOR‐dependent FoxO inhibition or by inducing the activity of autophagy‐related (ATG) proteins.

Mentions: A decrease in the uptake of nutrients produces an imbalance in the metabolic system. To return to a new equilibrium, several regulatory pathways interact. The new equilibrium responds to the relationship between growth‐associated pathways, such as the insulin–insulin growth factor‐1 (IGF‐I) receptor system and Target of Rapamycin (TOR), and regulators of a more efficient respiratory metabolism such as AMP‐dependent kinase (AMPK) and sirtuins, the NAD+‐dependent deacetylases. Interestingly, the relationship between these mechanisms is conserved during evolution from yeasts to humans. In simple terms, the decrease in calories in the diet activates systems involved in a more efficient metabolism, a higher protection against cellular damage and the activation of remodelling mechanisms, whereas less efficient metabolism and synthetic pathways are blocked. Interestingly, these mechanisms regulate each other in all the organisms studied, indicating that CR activates an evolutionarily conserved response that avoids fruitless energy expenditure and use recycled structures for the organisms’ survival (Fig. 2). In this section we provide a resumé of the main molecular mechanisms involved in the CR effect on lifespan and healthspan (more detailed information can be found in Michan, 2014; Testa et al. 2014).


Calorie restriction as an intervention in ageing.

López-Lluch G, Navas P - J. Physiol. (Lond.) (2016)

Complex interaction of proliferative and protective mechanisms in the CR prolongevity effect in organismsNearly all the organisms studied to date have shown similar mechanisms in response to CR. Basically, CR induces mechanisms involved in energy efficacy and inhibits mechanisms involved in less efficient energy consumption and proliferation. Thus, CR inhibits IGF‐I‐dependent signalling which activates TOR and protein synthesis and inhibits FoxO, blocking antioxidant expression and autophagy. On the other hand, the balance between AMP and ATP and NAD+ and NADH serves as a signal to activate AMPK and sirtuins, respectively. These nutrient sensors and regulators block the signal dependent on IGF‐I and TOR at the same time as they activate mechanisms to enhance more efficient energy production through oxidative metabolism and mechanisms to enhance cell protection through antioxidants and organelle turnover through autophagy. At the same time, CR, through sirtuins, can block inflammation mediators. This regulation occurs at different levels and many mediators can produce a redundant response such as autophagy activation by blocking TOR‐dependent FoxO inhibition or by inducing the activity of autophagy‐related (ATG) proteins.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834802&req=5

tjp6990-fig-0002: Complex interaction of proliferative and protective mechanisms in the CR prolongevity effect in organismsNearly all the organisms studied to date have shown similar mechanisms in response to CR. Basically, CR induces mechanisms involved in energy efficacy and inhibits mechanisms involved in less efficient energy consumption and proliferation. Thus, CR inhibits IGF‐I‐dependent signalling which activates TOR and protein synthesis and inhibits FoxO, blocking antioxidant expression and autophagy. On the other hand, the balance between AMP and ATP and NAD+ and NADH serves as a signal to activate AMPK and sirtuins, respectively. These nutrient sensors and regulators block the signal dependent on IGF‐I and TOR at the same time as they activate mechanisms to enhance more efficient energy production through oxidative metabolism and mechanisms to enhance cell protection through antioxidants and organelle turnover through autophagy. At the same time, CR, through sirtuins, can block inflammation mediators. This regulation occurs at different levels and many mediators can produce a redundant response such as autophagy activation by blocking TOR‐dependent FoxO inhibition or by inducing the activity of autophagy‐related (ATG) proteins.
Mentions: A decrease in the uptake of nutrients produces an imbalance in the metabolic system. To return to a new equilibrium, several regulatory pathways interact. The new equilibrium responds to the relationship between growth‐associated pathways, such as the insulin–insulin growth factor‐1 (IGF‐I) receptor system and Target of Rapamycin (TOR), and regulators of a more efficient respiratory metabolism such as AMP‐dependent kinase (AMPK) and sirtuins, the NAD+‐dependent deacetylases. Interestingly, the relationship between these mechanisms is conserved during evolution from yeasts to humans. In simple terms, the decrease in calories in the diet activates systems involved in a more efficient metabolism, a higher protection against cellular damage and the activation of remodelling mechanisms, whereas less efficient metabolism and synthetic pathways are blocked. Interestingly, these mechanisms regulate each other in all the organisms studied, indicating that CR activates an evolutionarily conserved response that avoids fruitless energy expenditure and use recycled structures for the organisms’ survival (Fig. 2). In this section we provide a resumé of the main molecular mechanisms involved in the CR effect on lifespan and healthspan (more detailed information can be found in Michan, 2014; Testa et al. 2014).

Bottom Line: CR produces a pleiotropic effect and improves multiple metabolic pathways, generating benefits to the whole organism.Finally, the anti-inflammatory effect of CR is an interesting emerging factor to be taken into consideration.In the present revision we focus on the general effect of CR and other mimetics in longevity, focusing especially on the cardiovascular system and skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto de Salud Carlos III, Carretera de Utrera km. 1, 41013, Sevilla, Spain.

No MeSH data available.


Related in: MedlinePlus