Overview of caloric restriction and ageing

Masoro, Edward J.

doi:10.1016/j.mad.2005.03.012

Cited by 945 publications

(783 citation statements)

References 88 publications

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“…However, the birds 16 bred only 3 times during the study period, and other studies have shown that the cost of reproduction for zebra finches rearing an un-manipulated brood size are small, even for birds breeding several times per year . As a final note, although we did not induce caloric restriction in the experimental birds, it is interesting to remark that the effects of unpredictability of food on survival observed in our study resemble lifespan extension found in caloric-restricted animals in several taxa (Masoro 2005). Since caloric restriction does increase baseline stress levels (Patel & Finch 2002), we could hypothesise that in a range of nutritional stressors or other mild and unpredictable environmental stressor, hormetic responses via moderate stimulation of the HPA axis may represent a conserved phenomenon that promotes survival and counteracts anti-ageing effects, even in the absence of body mass changes.…”

Section: Discussionsupporting

confidence: 55%

Repeated exposure to stressful conditions can have beneficial effects on survival

Marasco

Boner

Heidinger

et al. 2015

Experimental Gerontology

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Repeated exposure to stressful circumstances is generally thought to be associated with increased pathology and reduced longevity. However, growing lines of evidence suggest that the effects of environmental stressors on survival and longevity depend on a multitude of factors and, under some circumstances, might be positive rather than negative. Here, using the zebra finch (Taeniopygia guttata), we show that repeated exposure to stressful conditions (i.e. unpredictable food availability), which induced no changes in body mass, was associated with a decrease in mortality rate and an increase in the age of death. As expected, the treated birds responded to the unpredictable food supply by increasing baseline glucocorticoid stress hormone secretion and there were no signs of habituation of this hormonal response to the treatment across time. Importantly, and consistent with previous literature, the magnitude of hormone increase induced by the treatment was significant, but relatively mild, since the baseline glucocorticoid concentrations in the treated birds were substantially lower than the peak levels that occur during an acute stress response in this species. Taken together, these data demonstrate that protracted exposure to relatively mild stressful circumstances can have beneficial lifespan effects.Key-words. Chronic stress, unpredictable food availability, glucocorticoids, corticosterone, HPA axis, hormesis. IntroductionProtracted or repeated exposure to stressful stimuli, such as those experienced by individuals living in uncontrollable or highly unstable environments, can have wide ranging effects on animal physiology, but the extent to which these effects are adaptive is the subject of considerate debate (Broonstra 2013). In vertebrates, one of the main systems mediating responses to stressful environmental conditions is the Hypothalamic-Pituitary-Adrenal axis (HPA axis), which regulates both basal production and transient surges of circulating glucocorticoid stress hormones. Transient increases in circulating glucocorticoids are a highly conserved component of the vertebrate stress response and play a key role in initiating an array of metabolic changes intended to mobilise energy, including hepatic gluconeogenesis and inhibition of glucose uptake by peripheral tissues . These changes are thought to be vital for promoting short-term survival (Wingfield et al. 1998;Sapolsky 2000). At the same time, dynamic changes in basal level of glucocorticoids, such as those occurring across differing seasons within the same year in a variety of free-living vertebrate species, are also thought to be critical for survival (Romero 2002). Over a longer time scale, however, the repeated activation of the HPA axis may lead to a dysregulation and dysfunction of the stress axis (Sapolsky 2000).The predominant view is that repeated stress exposure, and the consequent prolonged elevation of glucocorticoid levels, is harmful since it can induce a large variety of downstream negative effects, including impairment of brai...

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Section: Discussionsupporting

confidence: 55%

Repeated exposure to stressful conditions can have beneficial effects on survival

Marasco

Boner

Heidinger

et al. 2015

Experimental Gerontology

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“…Interestingly, nearly all of these hepatic genes (30 of 33) were similarly regulated by caloric restriction, a proven method of extending lifespan in mice and other species (Masoro, 2005; Bishop and Guarente, 2007; Kenyon, 2010). In contrast, there was little or no overlap in the genes regulated by FGF21 and caloric restriction in muscle or adipose.…”

Section: Discussionmentioning

confidence: 99%

“…Caloric restriction without malnutrition is a proven means of inhibiting aging in species ranging from worms to nonhuman primates (Masoro, 2005; Bishop and Guarente, 2007; Kenyon, 2010). The effect of caloric restriction on longevity appears to be mediated by multiple nutrient-sensing pathways including those involving insulin and insulin-like growth factor (IGF-1), target of rapamycin (TOR), AMP kinase and sirtuins.…”

Section: Introductionmentioning

confidence: 99%

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Zhang

Xie

Berglund

et al. 2012

eLife

336

266

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Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI: http://dx.doi.org/10.7554/eLife.00065.001

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“…The oldest model for extending life span is the reduction of caloric intake (Masoro, 2005). Caloric restriction typically refers to a diet in which calories are limited by 30-40 % compared with animals fed ad lib.…”

Section: Introductionmentioning

confidence: 99%

Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues

Garcı́a

Busuttil

Calder

et al. 2008

Mechanisms of Ageing and Development

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Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduces multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into E. coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57Bl/6 background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7-and 15-month old mice of all four cohorts. A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR.

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Overview of caloric restriction and ageing

Cited by 945 publications

References 88 publications

Repeated exposure to stressful conditions can have beneficial effects on survival

Repeated exposure to stressful conditions can have beneficial effects on survival

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues

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