mTOR is a hot topic in aging research these days, at least for those parts of the community seeking to develop drugs capable of modestly slowing the aging process. As a goal this is something that I think isn't really worth the time and money poured into it, not when there are other paths ahead based on repairing the causes of aging, capable of producing the far better outcome of rejuvenation and restored health. Persuading the research community on this topic is an ongoing project, led by organizations such as the SENS Research Foundation.
Rapamycin is one drug candidate shown to slow aging in laboratory species, but it affects both mTORC1 and mTORC2 to cause beneficial and harmful effects in equal measure - it isn't something you'd want to take if you had any choice in the matter. Thus researchers focus on intervening in mTORC1, and rapamycin should probably be considered a tool for investigation rather than an actual drug candidate. Like many areas of research into metabolism and aging, this is also relevant to cancer research:
mTOR is a serine/threonine kinase found in two complexes, mTORC1 and mTORC2. mTORC1 coordinates cell growth and metabolism in response to environmental stresses, nutrient and energy levels, growth factors and other conditions. Rapamycin extends life span of wild type mice, possibly through cancer suppression since mTORC1 signaling is often dysregulated in cancer cells. Dietary rapamycin also ameliorated general aging in wild type mice for most, but not all studies. Rapamycin also extended life span for lower organisms that do not die from cancer suggesting that rapamycin suppresses general aging in addition to cancer. Thus, rapamycin appears to suppress mTORC1-mediated oncogenesis and possibly general aging.
p53 is a transcription factor with broad biological function that is best known for suppressing tumors in humans and mice by inducing cell cycle arrest, apoptosis and senescence in response to a variety of stresses. p53 inhibits mTORC1 and thus suppresses mTORC1-driven cell growth in response to cellular stresses like DNA damage.
We provide three lines of evidence that support the notion that p53 and rapamycin are additive. First, p53 enabled enterically targeted rapamycin to extend life span in mice. Second, p53 facilitated the ability of rapamycin to suppress radiation-induced amino acid and citric acid levels in mouse embryonic stem cells. Thus, there appears to be an augmentative relationship between p53 and rapamycin.
We suggest that p53 and rapamycin blunt mTORC1 activity through different pathways to result in this additive relationship.
This contention is relevant to the use of mTORC1 inhibitors as anti-cancer therapeutics since p53 is mutated or dysfunctional in most cancers. mTORC1 inhibitors might be most effective early in the oncogenic process, before p53 is mutated. Our previous results support this possibility since we found that rapamycin suppressed the development of tumors with wild type p53. High levels of mTORC1 inhibitor might be needed to overcome cancer with p53-null mutations. Yet for those p53-dysfunctional cancers that have a functional p53 protein, mTORC1 inhibitors coupled with p53 enablers such as nutlin could be a powerful combination allowing a lower dose for each.