Timothy R. Peterson | Searcharxiv

arXiv2019

Moonshots for aging

As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans. With space travel, scientists couldn't know what it would take to get to the moon. They had to extrapolate from theory and shorter-range tests. Perhaps with aging, we need a similar moonshot philosophy. And though "shot" might imply medicine, perhaps we need to think beyond biological interventions. Like the moon, we seem a long way away from provable therapies to increase human healthspan (the healthy period of one's life) or lifespan (how long one lives). This review therefore focuses on radical proposals. We hope it might stimulate discussion on what we might consider doing significantly differently than ongoing aging research.

q-bio.OT↗

arXiv2015

mTORC1 regulates cytokinesis through activation of Rho-ROCK signaling

Understanding the mechanisms by which cells coordinate their size with their ability to divide has long attracted the interest of biologists. The Target of Rapamycin (TOR) pathway is becoming increasingly recognized as a master regulator of cell size, however less is known how TOR activity might be coupled with the cell cycle. Here, we establish that mTOR complex 1 (mTORC1) promotes cytokinesis through activation of a Rho GTPase-Rho Kinase (ROCK) signaling cascade. Hyperactivation of mTORC1 signaling by depletion of any of its negative regulators: TSC1, TSC2, PTEN, or DEPTOR, induces polyploidy in a rapamycin-sensitive manner. mTORC1 hyperactivation-mediated polyploidization occurs by a prolonged, but ultimately failed attempt at abcission followed by re-fusion. Similar to the effects of ROCK2 overexpression, these mTORC1-driven aberrant cytokinesis events are accompanied by increased Rho-GTP loading, extensive plasma membrane blebbing, and increased actin-myosin contractility, all of which can be rescued by either mTORC1 or ROCK inhibition. These results provide evidence for the existence of a novel mTORC1-Rho-ROCK pathway during cytokinesis and suggest that mTORC1 might play a critical role in setting the size at which a mammalian cell divides.

q-bio.SC↗