Are SIRT1, SIRT3 and SIRT6 the skin’s anti-aging trinity?

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Sirtuin biology is gaining ground in the nutricosmetics and healthy aging space as researchers map how these enzymes regulate cellular structure and function in skin.

Speaking with NutraIngredients at the recent Nutra Healthspan Summit in London, Dr. Rishabh Kala, director of advanced technologies at Estée Lauder Companies, discussed emerging findings from the company’s long-running sirtuin program and how the pathways intersect with nutrition, metabolism and topical care.

Core sirtuins tied to aging hallmarks

Much of Estée Lauder’s work centers on SIRT1, SIRT3 and SIRT6, which Dr. Kala said are positioned at cellular sites relevant to transcription, mitochondrial activity and genomic maintenance.

“The reason why SIRT1, SIRT3 and SIRT6 are the major players in this space is first, because of their location in the cell,” he said. SIRT1 supports nuclear processes, SIRT3 sits within mitochondria, where age-related decline is well documented, and SIRT6 is associated with DNA stability.

According to Dr. Kala, the combined activity of the three enzymes allows researchers to examine multiple aging mechanisms at once.

“Overall when we use SIRT1, SIRT3 and SIRT6 together, it’s like holistic attack on the aging cell,” he said, adding that this activity strengthens the skin barrier and helps maintain resilience.

The company has built a substantial internal evidence base, with Dr. Kala stating, “We have been studying this for over 17 years now…it’s new to the world but not to us.”

SIRT2 draws attention for structural effects

Beyond the better-known sirtuins, SIRT2 is becoming increasingly recognized as a potential regulator of cell shape and mechanical strength. Dr. Kala described it as “a new emerging sirtuin,” noting its contribution to maintaining elongated, structured cells typical of younger skin.

“Aging skin cells become more circular, younger skin is more elongated, and cells are more bouncy,” he explained. “Older skin loses its strength and elasticity partly due to a decline in SIRT2.”

He added that in the company’s current area of study, Estée Lauder researchers have have seen the main role of SIRT2 has been shown in cell morphology.

Metabolic requirements and intervention routes

As the category expands, NAD availability remains a foundational requirement for sirtuin activity.

“For sirtuins to function, NAD is a must,” Dr. Kala said.

He noted that achieving meaningful support often involves multiple approaches, explaining that “you have to take steps for improving your metabolism, you have to rely on some supplements, but you also need topical treatments.”

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