ArticleAging2012
Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging.
Article in Aging, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pooled it
- Chronic rapamycin treatment attenuates age-related motor deficits in sex-dependent manner in UM-HET3 mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Early-life cognitive intervention preserves brain function in aged TgF344-AD rats with sex-specific effects.iScience · 2026Article
- Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy.Aging cell · 2025Article
- Decreasing Intracellular Entropy by Increasing Mitochondrial Efficiency and Reducing ROS Formation-The Effect on the Ageing Process and Age-Related Damage.International journal of molecular sciences · 2024Review
- Article
- mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity.International journal of molecular sciences · 2022Review
- As predicted by hyperfunction theory, rapamycin treatment during development extends lifespan.Aging · 2022Article
- The hyperfunction theory: An emerging paradigm for the biology of aging.Ageing research reviews · 2022Review
- A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions.Frontiers in aging neuroscience · 2022Review
- Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats.Frontiers in cellular neuroscience · 2022Article
- Targeting age-specific changes in CD4Aging cell · 2021Article
- Alteration in cardiac PI3K/Akt/mTOR and ERK signaling pathways with the use of growth hormone and swimming, and the roles of miR21 and miR133.Biomedical reports · 2019Article
- Hamartoma-like lesions in the mouse retina: an animal model ofDisease models & mechanisms · 2018Article
- Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.Human molecular genetics · 2017Article
- USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors.Scientific reports · 2017Article
- Somatic growth, aging, and longevity.NPJ aging and mechanisms of disease · 2017Review
- Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs.Aging · 2016Article
- Article
- Inverse correlation between longevity and developmental rate among wild C. elegans strains.Aging · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Males, who are bigger and stronger than females, live shorter in most species from flies to mammals including humans. Cellular mass growth is driven in part by mTOR (Target of Rapamycin). When developmental growth is completed, then, instead of growth, mTOR drives aging, manifested by increased cellular functions, such as hyper-secretion by fibroblasts, thus altering homeostasis, leading to age-related diseases and death. We hypothesize that MTOR activity is elevated in male mice compared with females. Noteworthy, 6 months old males were 28 % heavier than females. Also levels of phosphorylated S6 (pS6) and phospho-AKT (p-AKT, Ser 473), markers of the mTOR activity, were higher in male organs tested. Levels of pS6 were highly variable among mice and correlated with body weight and p-AKT. With age, the difference between levels of pS6 between sexes tended to minimize, albeit males still had hyperactive mTOR. Unlike fasting, the intraperitoneal (i.p.) administration of rapamycin eliminated pS6 in all organs of all females measured by immunoblotting and immunohistochemistry without affecting p-AKT and blood insulin. Although i.p. rapamycin dramatically decreased levels of pS6 in males too, it was still detectable by immunoblotting upon longer exposure. Our study demonstrated that both tissue p-AKT and pS6 were higher in young male mice and were associated with increased body weight and insulin. These data can explain bigger body size and faster aging in males. Our data suggest higher efficacy of rapamycin compared to fasting. Higher sensitivity of females to rapamycin may explain more pronounced life extension by rapamycin observed in females compared to males in several studies.
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What OpenQuestion holds
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.