BMAL1-dependent regulation of the mTOR signaling pathway delays aging
What this study shows
Loss of the clock protein BMAL1 raised mTORC1 activity in mice and in cultured cells, and rapamycin extended the lifespan of Bmal1-/- mice by 50%. Places the circadian clock upstream of mTORC1 as a brake, and links that brake to ageing.
Abstract
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The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture.
Read the full abstract on PubMed →At a glance
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| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Bmal1-/- mice and fibroblasts); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Bmal1-/- mice and fibroblasts |
| Journal | Aging |
| Year | 2014 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.18632/aging.100633 · PMID 24481314 · Free full text (PMC3927809) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Pathway relations
Supports
Rapamycin activates LongevityStrongest evidence: A (Animal model) · settled in the literature · Status: Proposed
not tested in people
The lifespan result is mouse only. No human lifespan or healthspan trial is held in this corpus and EVERLAST has no results yet; the closest human survival data here, STE2026, is observational, at immunosuppressive doses in kidney…
People in the Atlas
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Circadian biologist who did her PhD in Roman Kondratov's lab at Cleveland State University, where she showed that the clock protein BMAL1 acts as a brake on mTORC1 and that feeding times set a daily rhythm in mTORC1 activity
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Showed the circadian clock protein BMAL1 gates TOR/mTOR signaling to control aging, and that calorie restriction's lifespan benefits require a working circadian clock
More: 5 other authors
No profile yet: Kondratova AA, Patel S, Dubrovsky Y, Wrobel M, Antoch MP
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Bmal1 knockout; rapamycin treatment |
| Target | mTORC1; BMAL1 |
| Model | Mouse |
| Effect | BMAL1 deficiency increases mTORC1 activity; rapamycin extends Bmal1-/- lifespan by 50% |
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