Hormonal
Reduced insulin/insulin-like growth factor (IIS) signaling extends lifespan and healthspan in model organisms but is associated with reduced skeletal muscle mass and function in aging humans.
Genetic studies show that dampening IGF-1 signaling can extend lifespan in mice, even if it reduces muscle size. However, in humans, low IGF-1 is linked to sarcopenia and frailty. The key takeaway is not to suppress IGF-1 artificially, but to understand that the pathways driving muscle growth (like mTOR) are the same ones that, when chronically overactive, might accelerate aging. The goal is balance: maintaining muscle through exercise and adequate protein without necessarily maximizing anabolic signaling to the point of potential cellular stress.
reductions in IIS enhance lifespan and delay some aging-associated parameters yet perhaps results in small body size that is characterized by both reduced fat mass and potentially, proportionally smaller SkM mass.
Why this rating
Based on multiple genetic knockout models (Irs1-/-, S6K1-/-) and human observational data, though direct long-term human muscle function data in these specific mutants is noted as lacking.
Source
Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake
Adam P. Sharples et al. · Aging Cell · 2015
DOI 10.1111/acel.12342
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