Is there a molecular program that determines the length of life?
While aging was historically perceived a consequence of wear and tear, studies now reveal a multiplicity of mechanisms that promote longevity and delay the onset of age dependent disease.
Centerstage to research on longevity are two molecular pathways: the Ins/mTORC1 and the CDK4/6 inhibitor, p16INKA. In literature, p16 and mTORC1 are thought to intersect longevity by very different mechanisms. While mTORC1 accelerates aging by upregulating metabolism, p16 is thought to accelerate aging by promoting inflammatory processes via the senescence associated secretory phenotype (SASP).
The multiplicity of processes that intersect longevity presents a fundamental question. On one hand, a mechanistic is to be expected. And yet, one cannot but wonder: given the multiplicity of mechanisms involved in aging, how are aging mechanisms specify a different characteristic lifespan value? While mice die of old age after 2-3 years of life, fruit bats can live to the age of 40. Is there a molecular mechanism that programs lifespan values?
To investigate lifespan mechanisms, we take the side road. Rather than focusing on pathways that promote anabolic activity (e.g. mTORC1), we ask for the mechanisms that activate and inhibit mTORC1 to maintain the homeostasis of anabolic rates.