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How can caloric restriction mimetics activate sirtuins?

Sirtuins are a class of proteins that play a crucial role in regulating various cellular processes, including metabolism, DNA repair, and stress response. They have been linked to longevity and are believed to be involved in the aging process.

Caloric restriction mimetics (CRMs) are compounds that mimic the effects of caloric restriction, which is a dietary intervention known to extend lifespan in various organisms. CRMs activate sirtuins, particularly the most well-known member of the sirtuin family, SIRT1.

1. NAD+ synthesis

One of the primary mechanisms through which CRMs activate sirtuins is by increasing the levels of nicotinamide adenine dinucleotide (NAD+). NAD+ is a coenzyme that plays a crucial role in cellular energy metabolism and is required for sirtuin activity. CRMs, such as resveratrol and nicotinamide riboside, can enhance NAD+ synthesis, thereby promoting sirtuin activation.

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2. Allosteric activation

CRMs can also directly bind to sirtuins and induce conformational changes that enhance their enzymatic activity. This allosteric activation allows sirtuins to deacetylate target proteins more efficiently, leading to various downstream effects on cellular processes involved in aging and longevity.

3. Epigenetic modifications

Sirtuins are known to regulate gene expression through their ability to modify histones, which are proteins that package DNA. CRMs can stimulate sirtuin-mediated histone deacetylation, leading to changes in chromatin structure and gene expression patterns. These epigenetic modifications can influence cellular processes associated with aging and lifespan.

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In summary, caloric restriction mimetics activate sirtuins through mechanisms such as increasing NAD+ levels, allosteric activation, and epigenetic modifications. By activating sirtuins, CRMs have the potential to modulate various cellular processes and potentially extend lifespan.

Keywords: sirtuins, cellular, caloric, restriction, activate, various, processes, sirtuin, activation