Calorie restriction in rodents: Caveats to consider

Ingram, Donald K.; Cabo, Rafael de

doi:10.1016/j.arr.2017.05.008

Cited by 108 publications

(103 citation statements)

References 207 publications

(265 reference statements)

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“…The impact of hyperphagia on shortening lifespan of subordinate mice can be understood in light of the established effect on longevity attributed to calorie restriction (CR) (Balasubramanian, Howell & Anderson, 2017; Mitchell et al., 2014). Although the maximal benefits of CR depend on several contextual factors (i.e., species and strain (Ingram & de Cabo, 2017)), CR attenuates age‐associated metabolic diseases allowing to preserve metabolic flexibility and limiting lipodystrophy and hepatic metabolic consequences (Mitchell et al., 2014). It can be speculated then that the same mechanisms altered by CR to extend longevity might become altered in an opposing way in subordinate mice resulting in aberrant lipid metabolism and dyslipidemia (Sanghez et al., 2013, 2016), compromising metabolic efficiency and accelerating physical wasting, overall contributing to earlier mortality.…”

Section: Discussionmentioning

confidence: 99%

Social stress shortens lifespan in mice

et al. 2018

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SummaryStress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon.

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Section: Discussionmentioning

confidence: 99%

Social stress shortens lifespan in mice

et al. 2018

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“…Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, with consideration of potential detrimental effects, such as an increased risk of infections or infertility. Naturally, evidence from animal models does not perfectly reflect the human situation [80] and caveats should be carefully considered in terms of feasibility, duration, timing and stringency of the CR conditions [81]. Therefore, it should be further explored how these strategies can be implemented in the human lifestyle and as such may contribute to healthy aging.…”

Section: Discussionmentioning

confidence: 99%

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Kok

Lugt

Lute

et al. 2018

The Journal of Nutritional Biochemistry

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Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.

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“…Traditionally, diet composition and genetic background have been thought to have a marginal impact on life-span extension elicited by CR. More recently, studies in mice and nonhuman primates have revealed that the effect of CR on life-span extension is not universal (20). Indeed, certain mouse recombinant inbred strains show either little increase or deleterious effects on life span after CR (5).…”

Section: Caloric Restrictionmentioning

confidence: 99%

A time to fast

Francesco

Germanio

Bernier

et al. 2018

Science

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403

334

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Nutrient composition and caloric intake have traditionally been used to devise optimized diets for various phases of life. Adjustment of meal size and frequency have emerged as powerful tools to ameliorate and postpone the onset of disease and delay aging, whereas periods of fasting, with or without reduced energy intake, can have profound health benefits. The underlying physiological processes involve periodic shifts of metabolic fuel sources, promotion of repair mechanisms, and the optimization of energy utilization for cellular and organismal health. Future research endeavors should be directed to the integration of a balanced nutritious diet with controlled meal size and patterns and periods of fasting to develop better strategies to prevent, postpone, and treat the socioeconomical burden of chronic diseases associated with aging.

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Calorie restriction in rodents: Caveats to consider

Cited by 108 publications

References 207 publications

Social stress shortens lifespan in mice

Social stress shortens lifespan in mice

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

A time to fast

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