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How can caloric restriction mimetics affect gene expression?

Caloric restriction mimetics are compounds that mimic the effects of caloric restriction, a dietary intervention known to extend lifespan and improve healthspan in various organisms. These compounds have gained significant attention in the field of longevity research due to their potential to modulate gene expression and promote longevity.

Mechanisms of action

Caloric restriction mimetics exert their effects on gene expression through several mechanisms:

1. Activation of sirtuins: Sirtuins are a family of proteins that play a crucial role in regulating cellular processes related to aging and longevity. Caloric restriction mimetics, such as resveratrol, activate sirtuins, particularly SIRT1, which in turn modulate the expression of genes involved in metabolism, stress response, and lifespan extension.

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2. Activation of AMP-activated protein kinase (AMPK): AMPK is an energy-sensing enzyme that regulates cellular energy metabolism. Caloric restriction mimetics, such as metformin, activate AMPK, leading to changes in gene expression that promote cellular energy homeostasis and enhance longevity.

3. Inhibition of mechanistic target of rapamycin (mTOR): mTOR is a protein kinase that regulates cell growth, metabolism, and aging. Caloric restriction mimetics, such as rapamycin, inhibit mTOR signaling, resulting in altered gene expression patterns that promote cellular stress resistance and extend lifespan.

Effects on gene expression

Caloric restriction mimetics can affect gene expression in various ways:

1. Upregulation of antioxidant genes: Caloric restriction mimetics can upregulate the expression of genes involved in antioxidant defense, such as superoxide dismutase (SOD) and catalase. This leads to a reduction in oxidative stress and enhanced cellular protection against age-related damage.

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2. Modulation of inflammatory genes: Caloric restriction mimetics can modulate the expression of genes involved in inflammation, such as nuclear factor-kappa B (NF-κB) and interleukins. By reducing chronic low-grade inflammation, these compounds contribute to improved healthspan and longevity.

3. Activation of autophagy-related genes: Caloric restriction mimetics can activate genes involved in autophagy, a cellular process that removes damaged proteins and organelles. Enhanced autophagy promotes cellular rejuvenation and delays age-related decline.

4. Regulation of metabolism-related genes: Caloric restriction mimetics can influence the expression of genes involved in metabolism, including those related to glucose and lipid metabolism. This can lead to improved metabolic health and increased longevity.

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In summary, caloric restriction mimetics exert their effects on gene expression through various mechanisms, including activation of sirtuins, AMPK, and inhibition of mTOR. These compounds modulate the expression of genes involved in antioxidant defense, inflammation, autophagy, and metabolism, ultimately promoting longevity and improving healthspan.

Keywords: caloric, restriction, expression, mimetics, longevity, cellular, metabolism, related, involved