Sirtuins: The Guardians of Cellular Health an Antiaging Discovery v1
Sirtuins are a family of signaling proteins that play a crucial role in metabolic regulation1. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life1. From bacteria and archaea to eukaryotes, organisms encode one or more sirtuins in their genomes1.
What are Sirtuins?
Sirtuins are NAD±dependent histone deacetylases2. They regulate important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction2.
The name “sirtuin” comes from the yeast gene ‘silent mating-type information regulation 2’, the gene responsible for cellular regulation in yeast1. Humans have seven different sirtuins3, each with its unique role and function.
The Role of Sirtuins
Sirtuins are essential for maintaining cellular health3. They utilize NAD+ to maintain cellular health and turn NAD+ to nicotinamide (NAM)1. The dependence of sirtuins on NAD+ links their enzymatic activity directly to the energy status of the cell via the cellular NAD+:NADH ratio, the absolute levels of NAD+, NADH or NAM or a combination of these variables1.
Sirtuins can catalyze both deacetylation and ADP-ribosylation2. Their best-characterized activity is NAD±dependent lysine deacetylation, but recent studies demonstrated that some sirtuins also remove other acyl groups such as succinyl, malonyl, glutaryl, and long-chain fatty acyl groups2.
Sirtuins and Human Health
Sirtuins are considered potential targets for the treatment of human pathologies including neurodegenerative diseases, cardiovascular diseases, and cancer. Recent interest focusing on sirtuin modulators as epigenetic players in the regulation of fundamental biological pathways has prompted increased efforts to discover new small molecules able to modify sirtuin activity.
While these findings are promising, they are still in the research phase and have not yet resulted in widely available treatments or therapies. Always consult with a healthcare professional for advice on managing aging.
In conclusion, sirtuins are a fascinating area of study with the potential to unlock new treatments for a variety of diseases. As our understanding of these proteins continues to grow, so too does the promise they hold for the future of medicine.
The “Eureka” moment in anti-aging research with Sirtuins came when Nadine Pernodet, a biologist and senior vice president of Estée Lauder Companies (ELC) Research & Development division, was writing up her lab’s results on a family of anti-ageing proteins called sirtuins1. She came across a paper describing how one of these proteins localizes to the cell’s cytoskeleton1. This led her to realize the potential link between sirtuins and aging.
Preliminary research by ELC suggests that this sirtuin, called SIRT2, helps protect cells against the effects of ageing by maintaining their structural integrity and thus their function1. SIRT2 activity falls as we age, but Pernodet’s team’s ongoing work suggests that increasing it reduces the signs of cellular ageing and helps support skin’s natural mechanical properties1. These findings will be published soon.
This discovery is a significant milestone in understanding the role of sirtuins in the biology of the skin, and how they might be modulated with therapies to combat visible ageing1.
