Dietary Restriction and Cold Temperature Both Acutely Reduce Senescence in C. elegans

Yen, Kelvin; Mobbs, Charles V.

doi:10.2174/1876326x00701010008

Cited by 3 publications

(4 citation statements)

References 31 publications

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“…Despite these striking parallels between the two environmental manipulations, key differences exist. Temperature affects survival more dramatically than dietary manipulations (12,13). Additionally, we show that 4E-BP activity reduces survival under cold, whereas it is commonly linked with life extension in the context of diet and nutrient sensing (23,48).…”

Section: Discussionmentioning

confidence: 69%

“…5A). Temperature has long been known to be a powerful decelerator of mortality rate (12,13,42) (Fig. 5B).…”

Section: Significancementioning

confidence: 99%

“…Lifespan extension by cold is evolutionarily conserved-documented in poikilotherms, such as worms and flies, and homeotherms, including mammals (4, 6-11)-and more robust than well-studied interventions such as dietary restriction (12,13). However, the underlying mechanisms remain incompletely understood (10,14,15).…”

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confidence: 99%

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The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

Carvalho

Drago

Hoxha

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Changes in body temperature can profoundly affect survival. The dramatic longevity-enhancing effect of cold has long been known in organisms ranging from invertebrates to mammals, yet the underlying mechanisms have only recently begun to be uncovered. In the nematode Caenorhabditis elegans, this process is regulated by a thermosensitive membrane TRP channel and the DAF-16/FOXO transcription factor, but in more complex organisms the underpinnings of cold-induced longevity remain largely mysterious. We report that, in Drosophila melanogaster, variation in ambient temperature triggers metabolic changes in protein translation, mitochondrial protein synthesis, and posttranslational regulation of the translation repressor, 4E-BP (eukaryotic translation initiation factor 4E-binding protein). We show that 4E-BP determines Drosophila lifespan in the context of temperature changes, revealing a genetic mechanism for cold-induced longevity in this model organism. Our results suggest that the 4E-BP pathway, chiefly thought of as a nutrient sensor, may represent a master metabolic switch responding to diverse environmental factors.S tudies on the biological underpinnings of aging have uncovered numerous genetic and environmental factors regulating animal lifespan. Longevity-promoting genes include components of the insulin-like signaling pathway, the histone deacetylase Sir2, the GTPase Ras, TRP membrane channels, and transcription factors, among many others (1, 2). Environmental manipulations extending life include changes in nutrition (often referred to as caloric or dietary restriction), sexual/reproductive history, and ambient temperature (3-5).Of the factors known to impact aging, temperature is arguably the most promising. Lifespan extension by cold is evolutionarily conserved-documented in poikilotherms, such as worms and flies, and homeotherms, including mammals (4, 6-11)-and more robust than well-studied interventions such as dietary restriction (12, 13). However, the underlying mechanisms remain incompletely understood (10,14,15). In Caenorhabditis elegans, the effect of cold on survival involves the thermosensitive membrane channel TRPA-1 acting upstream of the DAF-16/FOXO transcription factor (14,15). This seminal finding countered the notion that longevity is the passive result of general thermodynamic changes, and favored instead the view that genetic pathways actively control lifespan in response to ambient temperature. However, these results have to date not been extended or replicated in other model organisms. Explanatory theories for the effect of cold on longevity include a reduction in reactive oxygen species generated by mitochondrial uncoupling proteins, suppression of autoimmune response, and changes in neuroendocrine factors (6,16,17), but these views remain largely speculative given the lack of further mechanistic insight into lifespan extension by cold in model organisms.We report that, in Drosophila, changes in temperature trigger a metabolic program impacting protein translation, mitochondrial prot...

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Section: Discussionmentioning

confidence: 69%

“…5A). Temperature has long been known to be a powerful decelerator of mortality rate (12,13,42) (Fig. 5B).…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

Carvalho

Drago

Hoxha

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Similarly, hypoglycemia and glucopenia can reduce body temperature in humans [60, 140] and other species [169] [20, 31, 153]. Reducing temperature dramatically increases lifespan in poikilothermic (cold-blooded) animals [40, 84, 112–116, 206, 220] but the effect in mammals has been challenging to determine. The most convincing evidence comes from Conti and colleagues, who produced transgenic mice with overexpression of uncoupling protein 2 (UCP2) specifically in the lateral hypothalamus [41].…”

Section: Examples Of Hypothalamic Top-down Control Of Two Specificmentioning

confidence: 99%

Role of the hypothalamus in mediating protective effects of dietary restriction during aging

Dacks

Moreno

Kim

et al. 2013

Frontiers in Neuroendocrinology

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Dietary restriction (DR) can extend lifespan and reduce disease burden across a wide range of animals and yeast but the mechanisms mediating these remarkably protective effects remain to be elucidated despite extensive efforts. Although it has generally been assumed that protective effects of DR are cell-autonomous, there is considerable evidence that many whole-body responses to nutritional state, including DR, are regulated by nutrient-sensing neurons. In this review, we explore the hypothesis that nutrient sensing neurons in the ventromedial hypothalamus hierarchically regulate the protective responses of dietary restriction. We describe multiple peripheral responses that are hierarchically regulated by the hypothalamus and we present evidence for non-cell autonomous signaling of dietary restriction gathered from a diverse range of models including invertebrates, mammalian cell culture, and rodent studies.

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Chemosensory and caloric mechanisms influence distinct components of mortality rate

Yen

Mobbs

2008

Experimental Gerontology

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Dietary Restriction and Cold Temperature Both Acutely Reduce Senescence in C. elegans

Cited by 3 publications

References 31 publications

The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

Role of the hypothalamus in mediating protective effects of dietary restriction during aging

Chemosensory and caloric mechanisms influence distinct components of mortality rate

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