Sirtuins Hold The Key To Longevity

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Circadian rhythms are linked to sirtuins, which are NAD-dependent longevity genes that aid in the repair of broken DNA and the extension of life. Sirtuins monitor cellular energy balance and influence the circadian epigenome[iii].

NAD+, a coenzyme required for physiological functions and energy production, regulates metabolism and circadian rhythms via sirtuins. Circadian rhythm disruption reduces the NAD+ dependent SIRT1 gene, lowering NAD+ availability[iv]. NAD levels decline with age, and lower NAD levels may hasten to age. It will undoubtedly reduce your energy potential.

SIRT1 is the primary sirtuin gene that regulates circadian rhythms and links them to cellular metabolism[v]. In mice, SIRT1 also slows aging and increases lifespan[vi]. Increased SIRT1 activity can also offer a wide range of health benefits in humans[vii].

Because of autophagy and sirtuins, calorie restriction and fasting increase lifespan. If you don’t activate them, either due to overeating or circadian misalignment, you may miss out on their benefits[viii][ix]. That is why time-restricted feeding and intermittent fasting can have distinct metabolic effects that prevent aging.

Clock Control Dependent on Sirtuins
All of your body’s cells and organs have biological clocks that are controlled by the suprachiasmatic nucleus (SCN) in your brain[x]. They react to light, temperature, movement, EMFs, food, and other stimuli. The circadian clock is a biological pacemaker that operates on a 24-hour cycle and maintains inner homeostasis or balance[xi].

Sirtuins have been shown to regulate the brain’s circadian clock and peripheral clocks in the liver, heart, and other organs[xii].

SIRT1 is hypothesized to act as an enzymatic rheostat of circadian processes, transmitting signals from cellular metabolites to the master clock[xiii]. SIRT1 plays an essential function in determining the metabolic status of the entire organism.

SIRT6 regulates the circadian clock of the liver[xiv]. It also stimulates DNA repair, and in mice, the lack of SIRT6 causes age and degeneration[xv].

NAD+ Metabolism During the Day
The circadian clock CLOCK, which is a histone acetyltransferase, drives the circadian cycles of NAD+. CLOCK: BMAL1 controls the circadian production of NAMPT (nicotinamide phosphoribosyltransferase), an enzyme required for the rate-limiting step in the NAD+ salvage pathway[xvi]. SIRT1 stimulates NAMPT and aids in the circadian manufacture of its enzyme. The ‘NAD World’ is the name given to this regulatory network.

NAD is metabolized by NAD-consuming enzymes, sirtuins, PARPs, and CD38 [xvii]. This reduces intracellular NAD+ biosynthesis while increasing nicotinamide production (NAM). The NAD salvage pathway recycles NAM into NAD. NAMPT converts NAM to nicotinamide mononucleotide (NMN), and NMN is transformed to NAD by nicotinamide mononucleotide adenylyltransferases 1–3 (NMNAT1–3)[xviii]. This is an incredible technique for your body to generate and recycle its energy.

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