Studying sirtuin inhibitors with in silico and in vitro approaches
Abstract
Caloric restriction (CR) is the kind of diet where the intake of calories is suppressed but the amount of nutrients is maintained; it has long been touted as the recipe for a longer lifespan.After the yeast enzyme silent information regulator 2 (Sir2) was found to be responsible for the longevity effects of CR, the search commenced to identify its analogues in mammals.Even though the roles of mammalian Sir2 relatives, sirtuins 1-7 (SIRT1-7), in CR and lifespan extension have not been definitely confirmed, sirtuins have become a major research target in health sciences.The function of sirtuins is linked to a wide variety of cellular functions, such as gene expression, energy production and adaptation to environmental stimuli.Sirtuins form the class III of histone deacetylase enzymes (HDACs).They affect the function of their target proteins by mediating the deacetylation of lysine residues.During the last few years, some sirtuin subtypes have also been shown to possess other catalytic activities, such as demyristoylation and desuccinylation.All catalytic mechanisms of sirtuins involve the cofactor nicotinamide adenine dinucleotide (NAD + ).NAD + is a biomarker for cellular metabolism, and it is the utilization of this cofactor which places sirtuins in the crossroads of metabolism, gene expression and protein function.The involvement of sirtuins in a wide variety of biological processes has triggered the search for sirtuin modulators, which could elucidate the physiological…
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Evidence Hub reads this as a thesis, done in cell cultures (in vitro) and computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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