ReviewBiochimica et biophysica acta2009
Extreme-longevity mutations orchestrate silencing of multiple signaling pathways.
Review in Biochimica et biophysica acta, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Why we age.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Biological Restraints on Indefinite Survival.Cold Spring Harbor perspectives in medicine · 2023Review
- A Complex Systems Perspective on Neuroimaging Studies of Behavior and Its Disorders.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Review
- Recent Advances in the Systems Biology of Aging.Antioxidants & redox signaling · 2018Review
- Article
- A recent global selective sweep on the age-1 phosphatidylinositol 3-OH kinase regulator of the insulin-like signaling pathway within Caenorhabditis remanei.G3 (Bethesda, Md.) · 2014Article
- Extreme Depletion of PIP3 Accompanies the Increased Life Span and Stress Tolerance of PI3K-null C. elegans Mutants.Frontiers in genetics · 2013Article
- Effects of ADARs on small RNA processing pathways in C. elegans.Genome research · 2012Article
- Mechanistic insights into aging, cell-cycle progression, and stress response.Frontiers in physiology · 2012Article
- A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat.Frontiers in genetics · 2011Article
- Expression level drives the pattern of selective constraints along the insulin/Tor signal transduction pathway in Caenorhabditis.Genome biology and evolution · 2011Article
- Genetic studies reveal the role of the endocrine and metabolic systems in aging.The Journal of clinical endocrinology and metabolism · 2010Review
- Integrating evolutionary and molecular genetics of aging.Biochimica et biophysica acta · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Long-lived mutants provide unique insights into the genetic factors that limit lifespan in wild-type animals. Most mutants and RNA interference targets found to extend life, typically by 1.5- to 2.5-fold, were discovered in C. elegans. Several longevity-assurance pathways are conserved across widely divergent taxa, indicating that mechanisms of lifespan regulation evolved several hundred million years ago. Strong mutations to the C. elegans gene encoding AGE-1/PI3KCS achieve unprecedented longevity by orchestrating the modulation (predominantly silencing) of multiple signaling pathways. This is evident in a profound attenuation of total kinase activity, leading to reduced phosphoprotein content. Mutations to the gene encoding the catalytic subunit of PI3K (phosphatidylinositol 3-kinase) have the potential to modulate all enzymes that depend on its product, PIP3, for membrane tethering or activation by other kinases. Remarkably, strong mutants inactivating PI3K also silence multiple signaling pathways at the transcript level, partially but not entirely mediated by the DAF-16/FOXO transcription factor. Mammals have a relatively large proportion of somatic cells, and survival depends on their replication, whereas somatic cell divisions in nematodes are limited to development and reproductive tissues. Thus, translation of longevity gains from nematodes to mammals requires disentangling the downstream consequences of signaling mutations, to avoid their deleterious consequences.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.