ArticleAging cell2020
Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Host Gnmt coordinates with Limosilactobacillus reuteri to alleviate ionizing radiation injury via microbiota remodeling and metabolic regulation in Drosophila melanogaster.Archives of microbiology · 2026Article
- The GNMT N-terminus Couples Folate Feedback to Methyl-donor Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Increased Glycine-N-methyltransferase expression disrupts light-dependent gene expression rhythms in the Drosophila eye.Journal of cell science · 2026Article
- Life-extending interventions do not necessarily result in compression of morbidity: a case example offering a robust statistical approach.GeroScience · 2026Article
- Dietary pyrroloquinoline quinone and spermidine in healthy longevity: targeting the hallmarks of aging.Frontiers in aging · 2026Review
- Calorie restriction mimetics against aging and inflammation.Biogerontology · 2025Review
- An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.PLoS genetics · 2025Article
- Dietary methionine restriction started late in life promotes healthy aging in a sex-specific manner.Science advances · 2025Article
- Remodeling of Cellular Respiration and Insulin Signaling Are Part of a Shared Stress Response in Divergent Bee Species.Insects · 2025Article
- A Head-Specific Transcriptomic Study Reveals Key Regulatory Pathways for Winter Diapause in the Mosquito Culex pipiens.Archives of insect biochemistry and physiology · 2025Article
- Serine metabolism in aging and age-related diseases.GeroScience · 2025Review
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- Transcription profiling reveals tissue-specific metabolic pathways in the fat body and ovary of the diapausing mosquito Culex pipiens.Comparative biochemistry and physiology. Part D, Genomics & proteomics · 2024Article
- Spermidine is essential for fasting-mediated autophagy and longevity.Nature cell biology · 2024Article
- Transcriptional control of a metabolic switch regulating cellular methylation reactions is part of a common response to stress in divergent bee species.The Journal of experimental biology · 2024Article
- Article
- Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan in Drosophila.Nature communications · 2023Article
- Chromosomal Instability Causes Sensitivity to Polyamines and One-Carbon Metabolism.Metabolites · 2023Article
- A brain-wide form of presynaptic active zone plasticity orchestrates resilience to brain aging in Drosophila.PLoS biology · 2022Article
- The landscape of aging.Science China. Life sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reduced insulin/IGF signaling (IIS) extends lifespan in multiple organisms. Different processes in different tissues mediate this lifespan extension, with a set of interplays that remain unclear. We here show that, in Drosophila, reduced IIS activity modulates methionine metabolism, through tissue-specific regulation of glycine N-methyltransferase (Gnmt), and that this regulation is required for full IIS-mediated longevity. Furthermore, fat body-specific expression of Gnmt was sufficient to extend lifespan. Targeted metabolomics showed that reducing IIS activity led to a Gnmt-dependent increase in spermidine levels. We also show that both spermidine treatment and reduced IIS activity are sufficient to extend the lifespan of Drosophila, but only in the presence of Gnmt. This extension of lifespan was associated with increased levels of autophagy. Finally, we found that increased expression of Gnmt occurs in the liver of liver-specific IRS1 KO mice and is thus an evolutionarily conserved response to reduced IIS. The discovery of Gnmt and spermidine as tissue-specific modulators of IIS-mediated longevity may aid in developing future therapeutic treatments to ameliorate aging and prevent disease.
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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.