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Why are sirtuins considered key regulators of aging?

1. Energy metabolism: Sirtuins are involved in regulating energy metabolism by modulating the activity of enzymes involved in cellular energy production, such as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α). By promoting energy production and mitochondrial function, sirtuins help maintain cellular homeostasis and improve overall healthspan.

2. DNA repair: Sirtuins play a crucial role in maintaining genomic stability by promoting DNA repair mechanisms. They can directly deacetylate and activate enzymes involved in DNA repair, such as poly(ADP-ribose) polymerase 1 (PARP-1) and DNA-dependent protein kinase (DNA-PK). By enhancing DNA repair capacity, sirtuins help prevent the accumulation of DNA damage, which is a major contributor to aging and age-related diseases.

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3. Cellular senescence: Sirtuins are involved in regulating cellular senescence, a state of irreversible cell cycle arrest associated with aging. They can modulate the activity of several proteins involved in senescence, such as p53 and p16INK4a, and promote the clearance of senescent cells through autophagy. By regulating cellular senescence, sirtuins help maintain tissue homeostasis and delay the onset of age-related diseases.

4. Inflammation and oxidative stress: Sirtuins have anti-inflammatory and antioxidant properties, which help protect cells from damage caused by chronic inflammation and oxidative stress. They can modulate the activity of transcription factors involved in inflammation, such as nuclear factor-kappa B (NF-κB), and enhance the expression of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase. By reducing inflammation and oxidative stress, sirtuins contribute to healthy aging and longevity.

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Overall, sirtuins are considered key regulators of aging due to their involvement in multiple cellular processes that influence lifespan and healthspan. Modulating sirtuin activity through lifestyle interventions or pharmacological agents holds promise for promoting healthy aging and potentially extending lifespan.

Keywords: sirtuins, cellular, involved, regulating, energy, activity, repair, senescence, inflammation