Bench & Beyond: Stimulating Sirtuins' Antiaging Appeal

Sirtuin is a class of protein enzymes with potential antiaging effects in humans. The name comes from silent information regulator-2, or Sir2, the gene responsible for cellular regulation in yeast. Sirtuins are known to affect cellular metabolism in plants and animals, and therefore may play a role in manifestations of aging. But there are questions: Which particular sirtuin? What is the mechanism? How can humans intervene to regulate that mechanism externally? The answers would have great appeal to cosmetics manufacturers and users.

One source describes sirtuin as NAD-dependent histone deacetylases, which means they remove acetyl groups from histone tails, causing the histones to wrap more tightly around the DNA and interfere with the transcription of genes by blocking access by transcription factors. The overall result of histone deacetylation is a global (nonspecific) reduction in gene expression, the process by which the DNA sequence and other inheritable information in a gene is made into a protein or other functional gene product. A sirtuin is one of those proteins.

Normally, sirtuin activity in humans is inhibited when nicotinamide binds to a specific receptor site—thus the dependency of sirtuins on NAD or nicotinamide adenine dinucleotide. Drugs that interfere with this binding should increase sirtuin activity; also, the resveratrol found in red wine has been shown to inhibit this binding activity. Nicotinamide, the amide of niacin or vitamin B3, is used to treat arthritis. It also has demonstrated anti-inflammatory actions that may be of benefit in patients with inflammatory acne vulgaris. Nicotinamide, therefore, would appear to play a positive role in inhibiting inflammation but a negative role in aging. Are there other ways to stimulate sirtuins?

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