Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in<i>C. elegans</i>

Zhang, Yue; Lanjuin, Anne; Chowdhury, Suvagata Roy; Mistry, Meeta; Garcia, Carlos G. Silva; Weir, Heather J.; Lee, Chia-Lin; Escoubas, Caroline C.; Tabakovic, Emina; Mair, William

doi:10.1101/665190

Cited by 16 publications

(22 citation statements)

References 65 publications

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“…It is well‐established that changes in mitochondrial function can signal throughout organisms to extend C. elegans lifespan 70 . In addition, neuronal AMPK mediates longevity in C. elegans and is interconnected with other metabolic pathways that affect mitochondrial morphology 72 . Our results complement each of these findings and suggest that the PMF may be the source change that leads to signaling downstream to affect physiology.…”

Section: Discussionsupporting

confidence: 74%

Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance inC. elegans

et al. 2020

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Mitochondria are organelles that provide energy to cells. Matching energy supply with energy demand is coordinated through various processes and is critical for cellular adaptation and survival under changing conditions. Therefore, an organism's health depends not only on mitochondrial energy production, but on the ability to sense metabolic status and the ability of mitochondria to signal appropriately to use that energy. 1,2 The mechanisms through which cellular energy-related signaling can occur likely depend on the electrochemical gradient across the mitochondrial inner membrane (IM). Mitochondrial respiration results in a proton gradient across the IM known as the protonmotive force (PMF). Ultimately, respiratory complexes of the electron transport chain (ETC) convert chemical energy into electrical potential energy by pumping protons across the IM, creating this gradient. The PMF can then be consumed at ATP synthase,

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Section: Discussionsupporting

confidence: 74%

Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance inC. elegans

et al. 2020

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“…Also, Zhang et al . showed that the lifespan extension of s6k null mutant in C. elegans is suppressed by neuronal expression of s6k (Y. Zhang et al., 2019). While the nervous system of C. elegans is not organized into a brain with higher‐order structures and domains, our findings show that lifespan regulation by a small number of brain neurons may be an evolutionarily conserved phenomenon in the Drosophila brain, which shares functional analogous organization with higher organisms.…”

Section: Discussionmentioning

confidence: 99%

Lifespan regulation in α/β posterior neurons of the fly mushroom bodies by Rab27

Lien

Chen

et al. 2020

Aging Cell

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The desire for lifespan extension is a never-ending quest throughout human history. While extreme lifespans are likely limited genetically, environmental factors and acquired characteristics do affect the speed of degeneration and health span. As a result, lifespan is determined as the collective effect of internal and external factors, including the challenges of oxidative stress, the homeostasis of circulating metabolites, intake of energy and nutrients, and the allocation of resources among major life functions. Restriction of caloric intake is by far the most effective approach to extend lifespan in all species examined from yeast to non-human primates. Although its long-term effect is hard to evaluate in humans, caloric restriction has been shown to induce physiological changes that are similar to those observed in animal models. However, when energy intake is restricted, limited resources need to be relocated from growth and reproduction to maintain life-sustaining functions, resulting in trade-offs between

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“…AAK-2 (AMPK) is another crucial metabolic energy sensor that links nutrient availability to lifespan ( 18 ). AMPK regulates mTORC1 activity and shares downstream effectors of lifespan modulation with mTOR ( 87 ). AMPK can also regulate mammalian FOXO3 ( 88 ).…”

Section: Dietary Restriction Extends Lifespan In C Elegansmentioning

confidence: 99%

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

et al. 2020

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The Caenorhabditis elegans genome possesses homologs of about two-thirds of all human disease genes. Based on its physiological aging characteristics and superiority, the use of C. elegans as a model system for studies on aging, age-related diseases, mechanisms of longevity, and drug screening has been widely acknowledged in recent decades. Lifespan increasing mutations in C. elegans were found to delay aging by impinging several signaling pathways and related epigenetic modifications, including the insulin/IGF-1 signaling (IIS), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR) pathways. Interestingly, dietary restriction (DR) has been shown to increase the lifespan of numerous metazoans and protect them from multiple age-related pathologies. However, the underlying molecular mechanisms are unclear. In recent decades, C. elegans has been used as a unique model system for high-throughput drug screening. Here, we review C. elegans mutants exhibiting increased in lifespan and age-dependent changes under DR, as well as the utility of C. elegans for drug screening. Thus, we provide evidence for the use of this model organism in research on the prevention of aging.

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Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics inC. elegans

Cited by 16 publications

References 65 publications

Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance inC. elegans

Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance inC. elegans

Lifespan regulation in α/β posterior neurons of the fly mushroom bodies by Rab27

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

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