The mTORC1-autophagy pathway is a target for senescent cell elimination

Abstract

Cellular senescence has recently been established as a key driver of organismal ageing. The state of senescence is controlled by extensive rewiring of signalling pathways, at the heart of which lies the mammalian Target of Rapamycin Complex I (mTORC1). Here we discuss recent publications aiming to establish the mechanisms by which mTORC1 drives the senescence program. In particular, we highlight our data indicating that mTORC1 can be used as a target for senescence cell elimination in vitro. Suppression of mTORC1 is known to extend lifespan of yeast, worms, flies and some mouse models and our proof-of-concept experiments suggest that it can also act by reducing senescent cell load in vivo.

Keywords: Ageing; DNA damage; Senescence; Torin1; mTOR.

Fig. 1

Mice treated with Torin1 show reduced markers of senescence. a Diagram depicting the Torin1 treatment protocol. b, c Mouse liver samples were analysed for markers of DNA damage (γH2AX) and senescence-associated telomere-associated DNA damage foci (see co-localisation of telo-FISH probe and γH2AX)