mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Abstract

Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.

mTORC1 activity negatively regulates human hair follicle growth and pigmentation

“…This provided a first, clinically relevant phenomenological indication that the upregulation of intrafollicular mTORC1 activity (Fig 1A and B), independently from changes in TSC2 protein levels (Fig 1C and D), might somehow be involved in hair graying. Moreover, as cell and tissue aging typically is associated with increased mTORC1 activity levels (Fernandes & Demetriades, 2021; Mota‐Martorell et al , 2022), the increased p‐S6 protein expression supports the concept that the human HFPU undergoes premature aging processes during canities (Tobin & Paus, 2001; O'Sullivan et al , 2021).…”

Biologically Structured Water (BSW) - A Review (Part 1): Structured Water (SW) Properties, BSW and Redox Biology, BSW and Bioenergetics

“…Rapamycin inhibits mTOR, which regulates many cell functions, including glycolysis in the mitochondria. Inhibition of mTOR is associated with reduced aging and improved health [219][220][221][222][223][224][225]. Although these findings show indirect evidence, they suggest that reducing glycolysis levels, thereby reducing O2 consumption in cells, has a twofold effect.…”

“…Reduced O2 consumption within the mitochondria also reduces ROS generation from dysfunctional mitochondria and reduces membrane potential [216][217][218]. As membrane potential and glycolysis are reduced, and mTOR is inhibited, the cell increases its rate of autophagy and apoptosis [219][220][221][222][223][224][225]. As senescent cells are replaced due to autophagy and apoptosis, they shift back to a balanced contribution of mitochondrial and WR energy generation, improving health and longevity.…”

Extracellular Vesicles in Aging: An Emerging Hallmark?

“…The insulin/IGF-1 signaling, via the insulin receptor substrate (IRS) adapter, activates phosphoinositide 3-kinase (PI3-K), which, in turn, triggers Akt and mTOR-1 activation. The insulin/IGF1 pathway can be considered an antagonistic hallmark of aging, since reduced mTOR signaling has been associated with longevity, whereas the increased activation of mTOR signaling characterizes the aged phenotype [71].…”