SIRT1: Difference between revisions

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 By deacetylating nuclear factor-kappa B (NF-κB), a key regulator of inflammatory responses, SIRT1 modulates inflammation within cells, reducing the likelihood of chronic inflammation, a known contributor to aging and age-related diseases.
-=== SIRT1 Activators ===
+=== Activation of SIRT1 ===
-Several compounds are known to activate SIRT1, including resveratrol, a natural compound found in red wine and grapes. Resveratrol has gained considerable attention for its potential to extend lifespan and combat age-related diseases. However, the exact mechanism of action and the therapeutic potential of resveratrol and other SIRT1 activators are still under investigation.
+The activation of SIRT1 has been a focal point of research due to its potential to extend lifespan and alleviate age-related diseases. Several endogenous and exogenous factors and compounds have been identified to enhance the activity of SIRT1, impacting aging and metabolic health.
+==== Caloric Restriction ====
+Caloric restriction, without malnutrition, is known to be one of the most effective interventions to activate SIRT1, and thereby promote longevity and healthspan. This restriction in calorie intake induces an energy-deprived state, leading to the activation of AMP-activated protein kinase (AMPK), which subsequently activates SIRT1, fostering improved cellular metabolism, stress resistance, and reduced inflammation.
+==== Resveratrol ====
+Resveratrol, a polyphenolic compound found in grapes, berries, peanuts, and red wine, is one of the most studied SIRT1 activators. It mimics the effects of caloric restriction by modulating the same pathways and confers protective effects against various diseases, including cardiovascular and neurodegenerative diseases. While resveratrol has demonstrated promising results in activating SIRT1 in animal models, further research is needed to clarify its efficacy and optimal dosage in humans.
+==== NAD+ Precursors ====
+SIRT1 activity is closely linked to the cellular levels of NAD+, a critical coenzyme involved in cellular metabolism and energy production. Increasing NAD+ levels through supplementation with its precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), has been shown to activate SIRT1, potentially mitigating age-related decline in cellular function and metabolism.
+==== Exercise ====
+Regular physical activity has been implicated in the activation of SIRT1. Exercise-induced physiological stress boosts NAD+ levels, subsequently enhancing SIRT1 activity. This increased activity plays a role in the exercise-mediated improvements in mitochondrial function, insulin sensitivity, and anti-inflammatory responses.
+==== Fasting and Intermittent Fasting ====
+Fasting and intermittent fasting, like caloric restriction, create an energy-deprived state that leads to the activation of SIRT1. These dietary strategies have been shown to enhance SIRT1 activity, contributing to improvements in cellular health, metabolism, and longevity.
+==== SIRT1 Activating Compounds (STACs) ====
+Several synthetic and natural SIRT1 activating compounds (STACs) have been identified, including SRT1720, SRT2104, and quercetin. These compounds have been demonstrated to enhance SIRT1 activity, modulate metabolic processes, and extend lifespan in various animal models. However, the translational potential of these compounds to human health and longevity remains to be fully elucidated.