Calorie Restriction Mimetics are pharmacological agents or specific compounds designed to replicate the beneficial metabolic and longevity-promoting effects of dietary calorie restriction without necessitating a reduction in total caloric intake. These substances aim to activate the same survival pathways and cellular stress responses triggered by a state of nutrient scarcity. The clinical goal is to leverage the anti-aging and healthspan benefits associated with restricted energy intake, such as improved insulin sensitivity and reduced oxidative stress.
Origin
This concept emerged from extensive research in aging biology and endocrinology demonstrating that long-term calorie restriction significantly extends lifespan and healthspan in various model organisms. The term “mimetics” derives from the Greek word mimetikos, meaning imitative, signifying their function as imitators of the caloric restriction state. Identification of these agents focuses on molecular targets known to mediate the effects of fasting.
Mechanism
The primary mechanism involves the activation of key metabolic sensors, notably the sirtuin family of enzymes and the AMP-activated protein kinase pathway. By activating these pathways, mimetics promote cellular repair, enhance mitochondrial biogenesis, and shift the body’s energy balance toward catabolism and stress resistance. This modulation leads to improved glucose homeostasis, reduced systemic inflammation, and a cellular environment conducive to longevity.
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