What is the Origin of IGF-1 Signaling Attenuation?

The concept is a direct application of findings from longevity and gerontology research, where genetic and pharmacological manipulations that reduce components of the Insulin/IGF-1 signaling cascade have repeatedly been shown to extend lifespan and healthspan in various model organisms. This pathway is one of the most conserved mechanisms linking nutrient sensing to the rate of aging. Clinical practice utilizes this principle to manage metabolic risk and promote cellular repair processes.

What is the Mechanism of IGF-1 Signaling Attenuation?

Attenuation operates by reducing the overall concentration of circulating IGF-1 or by decreasing the sensitivity of its cellular receptors, often through dietary interventions like protein restriction or specific pharmacological agents. Lowered IGF-1 signaling shifts the cellular state from growth and anabolism towards maintenance and repair, specifically promoting processes like autophagy—the cellular self-cleaning mechanism. This shift enhances cellular resilience to stress and reduces the accumulation of damaged macromolecules, which are hallmarks of aging.

IGF-1 Signaling Attenuation

Meaning

This describes the deliberate, clinical strategy of reducing the activity or intensity of the Insulin-like Growth Factor 1 (IGF-1) signaling pathway within the body, a key regulator of cell growth, proliferation, and metabolism. While essential for development, sustained high levels of IGF-1 signaling are strongly correlated with accelerated cellular aging and increased risk for certain age-related pathologies. Attenuation aims to mimic the longevity-promoting effects observed in caloric restriction models by dampening this anabolic signal.