Longevity pathways are a set of highly conserved, interconnected cellular and molecular signaling cascades that regulate the aging process, cellular repair, and overall lifespan in organisms. These pathways respond dynamically to environmental cues, particularly nutrient availability and stress, influencing genetic expression to prioritize either growth and reproduction or maintenance and survival. Key pathways include mTOR, AMPK, sirtuins, and the insulin/IGF-1 signaling cascade, which are central targets for healthspan and lifespan optimization strategies.
Origin
The concept of specific “longevity pathways” emerged from groundbreaking genetic research, primarily in model organisms, which identified single-gene mutations capable of dramatically extending lifespan. This led to the discovery that a small number of evolutionarily conserved signaling cascades are responsible for regulating the rate of aging. The term is now widely used in biogerontology and translational medicine to describe the mechanisms that link lifestyle interventions to cellular health.
Mechanism
These pathways operate as master metabolic switches. For instance, when nutrient levels are high, the mTOR pathway is activated, promoting cell growth and protein synthesis. Conversely, during caloric restriction or fasting, the AMPK and sirtuin pathways are activated, which inhibits mTOR, enhances mitochondrial function, and stimulates DNA repair and autophagy, a cellular self-cleaning process. Hormones like insulin and growth hormone directly interface with the insulin/IGF-1 pathway, linking the endocrine system to the core machinery that dictates the pace of cellular aging.
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