Topic
Longevity Pathway
About: Longevity Pathway is a research topic. Over the lifetime, 41 publications have been published within this topic receiving 8119 citations.
Papers
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.
Abstract: We have found 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. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise 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. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.
3,465 citations
TL;DR: In this article, the authors found that mitochondrial perturbation in one tissue is perceived and acted upon by the mitochondrial stress response pathway in a distal tissue, which suggests that mitochondria may establish and perpetuate the rate of aging for the whole organism.
1,032 citations
TL;DR: It is demonstrated that MRPs represent an evolutionarily conserved protein family that ties the mitochondrial ribosome and mitonuclear protein imbalance to the mitochondrial unfolded protein response, an overarching longevity pathway across many species.
Abstract: Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity regulators. MRP knockdown triggers mitonuclear protein imbalance, reducing mitochondrial respiration and activating the mitochondrial unfolded protein response. Specific antibiotics targeting mitochondrial translation and ethidium bromide (which impairs mitochondrial DNA transcription) pharmacologically mimic mrp knockdown and extend worm lifespan by inducing mitonuclear protein imbalance, a stoichiometric imbalance between nuclear and mitochondrially encoded proteins. This mechanism was also conserved in mammalian cells. In addition, resveratrol and rapamycin, longevity compounds acting on different molecular targets, similarly induced mitonuclear protein imbalance, the mitochondrial unfolded protein response and lifespan extension in C. elegans. Collectively these data demonstrate that MRPs represent an evolutionarily conserved protein family that ties the mitochondrial ribosome and mitonuclear protein imbalance to the mitochondrial unfolded protein response, an overarching longevity pathway across many species.
1,004 citations
TL;DR: The C. elegans insulin/IGF-1 system integrates multiple signals to define the animal's rate of ageing, and this study demonstrates an inherent relationship between the reproductive state of this animal and its lifespan, and may have implications for the co-evolution of reproductive capability and longevity.
Abstract: Understanding how the ageing process is regulated is a fascinating and fundamental problem in biology. Here we demonstrate that signals from the reproductive system influence the lifespan of the nematode Caenorhabditis elegans. If the cells that give rise to the germ line are killed with a laser microbeam, the lifespan of the animal is extended. Our findings suggest that germline signals act by modulating the activity of an insulin/IGF-1 (insulin-like growth factor) pathway that is known to regulate the ageing of this organism. Mutants with reduced activity of the insulin/IGF-1-receptor homologue DAF-2 have been shown to live twice as long as normal, and their longevity requires the activity of DAF- 16, a member of the forkhead/winged-helix family of transcriptional regulators. We find that, in order for germline ablation to extend lifespan, DAF-16 is required, as well as a putative nuclear hormone receptor, DAF-12. In addition, our findings suggest that signals from the somatic gonad also influence ageing, and that this effect requires DAF-2 activity. Together, our findings imply that the C. elegans insulin/IGF-1 system integrates multiple signals to define the animal's rate of ageing. This study demonstrates an inherent relationship between the reproductive state of this animal and its lifespan, and may have implications for the co-evolution of reproductive capability and longevity.
1,002 citations
TL;DR: It is suggested that this network of tissue interactions and feedback regulation allows the tissues to equilibrate and fine-tune their expression of downstream genes, which, in turn, coordinates their rates of aging within the animal.
828 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 3 |
| 2020 | 2 |
| 2019 | 1 |
| 2018 | 1 |
| 2017 | 3 |
| 2016 | 1 |