Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension

Catterson, James H.; Khericha, Mobina; Dyson, Miranda C.; Vincent, Alec; Callard, Rebecca; Haveron, Steven M.; Rajasingam, Arjunan; Ahmad, Mumtaz; Partridge, Linda

doi:10.1016/j.cub.2018.04.015

Cited by 122 publications

(109 citation statements)

References 61 publications

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“…We propose that our dietary phenotypes may also be contingent upon the direction and degree in which these diets deviate from the optimum, which may be one explanation for the dissimilarity of results observed in similar experiments. These considerations may also explain why the precise duration of DR is important, in line with the recent finding that the duration of starvation is critical in the life-span extension generated via intermittent fasting (42). In addition, larval diet, timing, and the order of how diets were fluctuated contributed to differential mortality observed when fluctuating diet (43).…”

Section: Discussionsupporting

confidence: 54%

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

et al. 2020

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Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR.

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Section: Discussionsupporting

confidence: 54%

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

et al. 2020

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“…Importantly, this broad perspective does not restrict the adaptive significance of predictive plasticity produced by the IIS pathway to deep physiological switches associated with seasonal or annual changes in the environment. It is well-established in the laboratory that repeatedly switching the dietary treatment of flies causes very rapid, reversible changes in their mortality rates, consistent with acute and readily reversible responses of the underlying pathways to changes in dietary cues (Catterson et al, 2018;Mair, Goymer, Pletcher, & Partridge, 2003). To us, this suggests that this response and the pathways involved have evolved not just to indicate broad seasonal or annual shifts in the environment, but also much more immediate, fine-scale variation in conditions.…”

Section: A More G Ener Al Hyp Othe S Is For the E Voluti On Of Dr Pmentioning

confidence: 70%

“…during adulthood increased mortality risk, although a shorter period of fasting in early adulthood followed by ad libitum feeding actually increased life span (Catterson et al, 2018). This suggests some sort of time threshold between the onset of environmental change and physiological remodelling, which has also been proposed in other plastic responses to environmental change (e.g.…”

Section: Costs Of Plasticitymentioning

confidence: 82%

Dietary restriction and insulin‐like signalling pathways as adaptive plasticity: A synthesis and re‐evaluation

et al. 2019

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Dietary restriction (DR) under laboratory conditions generally extends life spanand delays ageing across species as diverse as yeast, nematode worms, flies and mice, and is underpinned by taxonomically conserved physiological pathways, notably the insulin-like signalling pathway (IIS). Despite growing excitement about the links between DR/IIS and ageing within biogerontology, our understanding of why the DR response and associated pathways evolved under natural selection remains controversial and limited.2. Here, we provide a brief overview of current understanding of the relationship between DR and IIS and ageing from modern biogerontology and go on to summarize the evidence that the IIS pathway integrates a range of important environmental cues including photoperiod, temperature and humidity, as well as nutrition.3. We go on to discuss the main existing evolutionary explanations for DR and argue that they are not mutually exclusive and are too nutrition-focussed to fully explain the evolutionary origin of the IIS pathway. In the wild, environmental cues and pressures are dynamic and multivariate, and physiological pathways capable of integrating multiple predictive cues could be strongly favoured by natural selection.4. We hypothesize that the IIS and related pathways, such as mTOR, evolved to detect and integrate a wide range of environmental cues (not just diet) that are predictive of important selective pressures in the wild. Available evidence suggests the pathway is capable of triggering a range of phenotypic responses, depending on the cues provided, ranging from profound physiological remodelling (e.g. diapause, aestivation, hibernation) associated with promoting survival through challenging environments, to more subtle responses to acute, fine-scale variation in the environment which may allow individuals to better match their level of reproductive investment to their conditions. 5. We argue that the IIS pathway underpins important adaptive phenotypic plastic responses to a wide range of environmental inputs, of which diet is just one. A multi-disciplinary approach combining perspectives and methods from biogerontology, cell biology, ecology and evolutionary biology will be essential to develop our understanding of the evolutionary origins of this pathway and the way natural K E Y W O R D S cues, mechanistic target of rapamycin (mTOR), natural selection, nutrient sensing, phenotypic plasticity, photoperiod, wild animals | 109 Functional Ecology REGAN Et Al.

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“…We show that bmm function is required in the somatic cells of the gonad and in neurons to maintain whole-body triglyceride homeostasis, provide the first evidence that bmm is sex-specifically regulated, and demonstrate the role of this regulation to the male-female difference in triglyceride homeostasis and starvation resistance. Given that the correct regulation of triglyceride homeostasis has also been linked with the regulation of sleep, fertility, reproduction, and feeding [23,36,37,43,72,[142][143][144][145][146][147][148], our studies raise the possibility that the male-female differences previously noted in at least some of these complex traits may be associated with the sex difference in Drosophila triglyceride homeostasis. Looking beyond Drosophila, it will be interesting to determine whether bmm also contributes to sex differences in triglyceride storage and breakdown in other animals because bmm homologs are found in many species [32,57,58,71].…”

Section: Discussionmentioning

confidence: 83%

A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown

et al. 2020

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Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.

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Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension

Cited by 122 publications

References 61 publications

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

Dietary restriction and insulin‐like signalling pathways as adaptive plasticity: A synthesis and re‐evaluation

A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown

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