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.
Highlights
Cellular senescence is a potent tumour suppressor mechanism that plays an important role in wound healing and development
We recently demonstrated that mammalian target of rapamycin complex 1 (mTORC1) dependency may represent a targetable vulnerability in senescent cells that could be used to eliminate them (Carroll et al 2017). mTORC1 is a master regulator of cell growth, the activity of which is tightly controlled by the balance between mitogenic and stress signals
In particular we recently demonstrated that mTORC1 activity is resistant to starvation of amino acids and growth factors in senescence which prevents starvation-induced activation of autophagy (Carroll et al 2017)
Summary
Cellular senescence is a potent tumour suppressor mechanism that plays an important role in wound healing and development. The central role of the mammalian target of rapamycin complex 1 (mTORC1) in driving senescence-associated phenotypes including SASP and increased mitochondrial content has been comprehensively established
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