The somatotrophic axis  in mammals comprises the growth hormone and his secondary mediator, the growth factor IGF-1.

The intracellular signaling pathway of IGF-1 is the same as that elicited by insulin which informs cells of the presence of glucose. The insulin and IGF-1 signaling (IIS) pathway is the most conserved aging-controlling factor in evolution. Among ISS-pathways’s targets there are some factors involved in aging .

Genetic polymorphisms or mutations that reduce the functions of GH, IGF-1 and insulin receptors are linked to longevity. In fact multiple genetic manipulations that attenuate signaling intensity at different levels of the IIS pathway consistently extend the lifespan of worms, flies and mice, as demonstrated by genetic analyses.

Consistent with relevance of deregulated nutrient sensing as a hallmark of aging , dietary restriction increases lifespan in all investigated  eukaryote species, including nonhumans primates.

Paradoxically, GH and IGF-1 levels decline during normal aging, so a decreased IIS is a common characteristic of both physiological and accelerated aging, whereas a constitutively decreased IIS extends longevity. This apparently contradictory situation can be explained under a unifying model by which IIS downmodulation reflects a defensive response aimed at minimizing cell growth and metabolism: organisms with a decreased IIS can survive longer because they have lower rates of cell growth and so lower rates of cell damage, but extremely low levels of IIS signaling are incompatible with life, as established by experiment.

In conclusion, current evidence supports the idea that  anabolic signaling accelerates aging and decreased nutrient signaling, but pharmacological manipulations that mimics a state of limited nutrient availability, such as rapamycin, can extend longevity in mice.