Lessons from C. elegans: signaling pathways for longevity
Louis R. Lapierre,Malene Hansen +1 more
TLDR
Three major endocrine- and nutrient-sensing signaling pathways with influence on lifespan, the insulin/insulin-like growth factor (IGF), target of rapamycin (TOR), and germline signaling pathways are reviewed, with special emphasis on the role of lipid metabolism and autophagy.Abstract:
Recent research using model organisms such as the nematode Caenorhabditis elegans has highlighted a crucial role for several conserved signaling pathways in longevity determination. Here, we review three major endocrine- and nutrient-sensing signaling pathways with influence on lifespan, the insulin/insulin-like growth factor (IGF), target of rapamycin (TOR), and germline signaling pathways. Although these pathways engage distinct sets of transcription factors, the three pathways appear to modulate aging in C. elegans through partially overlapping effector mechanisms, including lipid metabolism and autophagy. This review highlights the latest advances in our understanding of how the insulin/IGF-1, TOR, and germline signaling pathways utilize different transcription factors to modulate aging in C. elegans with special emphasis on the role of lipid metabolism and autophagy.read more
Citations
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Journal ArticleDOI
Metabolic Control of Longevity
TL;DR: The introduction of strategies that promote metabolic fitness may extend healthspan in humans as several metabolic alterations accumulate over time along with a reduction in biological fitness, suggesting the existence of a "metabolic clock" that controls aging.
Journal ArticleDOI
The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans
Louis R. Lapierre,C. Daniel De Magalhaes Filho,Philip R. McQuary,Chu-Chiao Chu,Orane Visvikis,Jessica T. Chang,Sara Gelino,Binnan Ong,Andrew Davis,Javier E. Irazoqui,Andrew Dillin,Malene Hansen +11 more
TL;DR: It is demonstrated that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan, and a conserved role for HLH -30 and TFEB in autophagy, and possibly longevity is demonstrated.
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease.
TL;DR: The breadth and depth of metabolic flexibility and its impact on health and disease are discussed and important advances in metabolic flexibility research are outlined and medical horizons and translational aspects are outlined.
Journal ArticleDOI
TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress*
Nina Raben,Rosa Puertollano +1 more
TL;DR: The participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysOSomal pathway in cellular adaptation to a variety of stress conditions, are discussed.
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Chronic kidney disease and premature ageing
TL;DR: It is proposed that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways.
References
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TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
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TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.
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A C. elegans mutant that lives twice as long as wild type
TL;DR: Finding that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type raises the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation.
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Extending Healthy Life Span-From Yeast to Humans
TL;DR: Dietary restriction and reduced activity of nutrient-sensing pathways may slow aging by similar mechanisms, which have been conserved during evolution, and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.