Gene Pathways That Delay Caenorhabditis elegans Reproductive Senescence

Wang, Meng C.; Oakley, Holly D.; Carr, Christopher E.; Sowa, Jessica N.; Ruvkun, Gary

doi:10.1371/journal.pgen.1004752

Cited by 44 publications

(54 citation statements)

References 32 publications

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“…Because of the crucial role of the reproductive system in regulating C. elegans longevity, we applied a high-throughput screening strategy different from the conventional method that interrupts reproduction. We selected the sqt-3(e2117) collagen mutant of C. elegans that reproduces normally but is embryonically lethal at 25 °C (Wang et al, 2014). Using this mutant, we performed the primary screen at the restrictive temperature to avoid labor-intensive animal transfer without interrupting normal reproduction (Figure S1D and E).…”

Section: Resultsmentioning

confidence: 99%

Microbial Genetic Composition Tunes Host Longevity

Han

Sivaramakrishnan

Lin

et al. 2017

Cell

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275

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Summary Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes, and a bacterial metabolite acting on host mitochondria to promote longevity.

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Section: Resultsmentioning

confidence: 99%

Microbial Genetic Composition Tunes Host Longevity

Han

Sivaramakrishnan

Lin

et al. 2017

Cell

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275

191

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“…Mutation of the daf-2 insulin/IGF-1 receptor increases C. elegans lifespan [34] and delays reproductive senescence [35, 36] and gonad degeneration [20, 37]. One possibility is that daf-2(−) suppresses gonad degeneration by reducing PA. daf-2 mutants fall broadly into two classes: class 1, e.g.…”

Section: Resultsmentioning

confidence: 99%

Run-on of germline apoptosis promotes gonad senescence inC. elegans

et al. 2016

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Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on the older theory of antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on of processes that in early life promote fitness. Here we apply this idea to investigate the etiology of senescent pathologies in the reproductive system of Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration. Hermaphrodite germ cells frequently undergo “physiological” (non-damage-induced) apoptosis (PA) to provision growing oocytes. Run-on of such PA is a potential cause of age-related gonad degeneration. We document the continuation of germline apoptosis in later life, and report that genetically blocking or increasing PA retards or accelerates degeneration, respectively. In wild-type males, which lack germ line apoptosis, gonad disintegration does not occur. However, mutational induction of PA in males does not lead to gonad disintegration. These results suggest that as germ-cell proliferation rate declines markedly in aging hermaphrodites (but not males), run-on of PA becomes a pathogenic mechanism that promotes gonad degeneration. This illustrates how hyperfunction, or non-adaptive run-on in later life of a process that promotes fitness in early life, can promote atrophic senescent pathology in C. elegans.

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“…In an evolutionary context, we assume that senescence is partially genetically determined (Kirkwood and Austad ; Patridge and Gems ; Nussey et al ; Kowald and Kirkwood ; Reichard ), and several studies have confirmed the heritability of individual senescence patterns (Arking ; Charmantier et al ; Wilson et al ; Wang et al ). The effect of developmental environment on reproductive senescence may therefore represent a “genotype by past‐environment” interaction.…”

Section: Discussionmentioning

confidence: 99%

Ageing with a silver-spoon: A meta-analysis of the effect of developmental environment on senescence

Cooper

Kruuk

2018

Evolution Letters

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What determines variation between individuals in how they senesce, and are environmental conditions experienced during development relevant to late‐life performance? We report a meta‐analysis of studies of wild populations to determine how the quality of the environment experienced during development affects rates of survival and reproductive senescence. From studies of 14 bird or mammal species, we calculated effect sizes for the interaction between the effects of environmental quality during development and age in predicting survival (N = 18) or reproduction (N = 30) over time in late life. We found no evidence that developmental environment affected rates of survival senescence (βmean = –1.2 × 10−4 ± 0.022SE). However, a better developmental environment was associated with slower rates of reproductive senescence in late life (βmean = 0.062 ± 0.023SE), indicating a small, but significant, “silver‐spoon” effect of early‐life conditions that persisted through to late life. Our results illustrate how the effects of environmental conditions during development can persist throughout life, and indicate one possible cause of phenotypic plasticity in senescence.

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Gene Pathways That Delay Caenorhabditis elegans Reproductive Senescence

Cited by 44 publications

References 32 publications

Microbial Genetic Composition Tunes Host Longevity

Microbial Genetic Composition Tunes Host Longevity

Run-on of germline apoptosis promotes gonad senescence inC. elegans

Ageing with a silver-spoon: A meta-analysis of the effect of developmental environment on senescence

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