ArticleCell metabolism2008
SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons.
Article in Cell metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 2 of them syntheses that pooled it.
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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.
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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
178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 330 citations in OpenAlex.
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- Sirtuins in kidney health and disease.Nature reviews. Nephrology · 2024Review
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- SIRT1, resveratrol and aging.Frontiers in genetics · 2024Review
- The role of deacetylase SIRT1 in allergic diseases.Frontiers in immunology · 2024Review
- Role of NADCellular and molecular neurobiology · 2023Review
- Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage.Molecular neurobiology · 2023Article
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- Hormonal regulation of metabolism-recent lessons learned from insulin and estrogen.Clinical science (London, England : 1979) · 2023Review
- Capsaicin protects against septic acute liver injury by attenuation of apoptosis and mitochondrial dysfunction.Heliyon · 2023Article
118 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Sirtuins are known to protect cells and extend life span, but our previous studies indicated that S. cerevisiae Sir2 can also increase stress sensitivity and limit life-span extension. Here we provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the sensitization of neurons to oxidative damage. SirT1 inhibition increased acetylation and decreased phosphorylation of IRS-2; it also reduced activation of the Ras/ERK1/2 pathway, suggesting that SirT1 may enhance IGF-I signaling in part by deacetylating IRS-2. Either the inhibition of SirT1 or of Ras/ERK1/2 was associated with resistance to oxidative damage. Markers of oxidized proteins and lipids were reduced in the brain of old SirT1-deficient mice, but the life span of the homozygote knockout mice was reduced under both normal and calorie-restricted conditions. These results are consistent with findings in S. cerevisiae and other model systems, suggesting that mammalian sirtuins can play both protective and proaging roles.
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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.