| First Author | Khapre RV | Year | 2014 |
| Journal | Aging (Albany NY) | Volume | 6 |
| Issue | 1 | Pages | 48-57 |
| PubMed ID | 24481314 | Mgi Jnum | J:206952 |
| Mgi Id | MGI:5553401 | Doi | 10.18632/aging.100633 |
| Citation | Khapre RV, et al. (2014) BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging (Albany NY) 6(1):48-57 |
| abstractText | 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. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism. |
