Centenarians carry a gene that slows cell aging

Senescent cells are cells that stop dividing but don’t die. They accumulate with age and release inflammatory signals that damage surrounding tissue. The researchers found that two linked variants in the SIRT6 gene, enriched in Ashkenazi Jewish centenarians, increase SIRT6 protein levels and slow the accumulation of senescent cells in aged tissue.

SIRT6 is an enzyme involved in DNA repair and gene regulation. The centenarian variants alter how the protein interacts with other molecules in the cell, including vimentin. Cells carrying these variants reach a senescent state later and show greater resistance to the cellular stress that typically accelerates aging. The researchers introduced these variants into human embryonic stem cells and tracked their effects across multiple cell types, providing a physiologically grounded picture of the mechanism.

Can the effect be reproduced?

The team tested whether the protective effect could be replicated. Delivering the centenarian SIRT6 variant via a viral vector (AAV-mediated gene therapy) reproduced key protective effects in cell culture. Pharmacological activation of SIRT6 using an existing compound showed similar results. These findings are preliminary and have not yet been tested in clinical settings.

The authors are explicit that the goal is not to replicate the exact biochemistry of centenarians. The real value is identifying which aging mechanisms matter most, so that more effective senotherapeutic strategies, those aimed at selectively clearing or neutralizing senescent cells, can be developed.

What comes next

The research strengthens the case for targeting cellular senescence in aging. Whether SIRT6 activation becomes a viable drug target in humans requires further investigation. For now, it offers one of the clearest mechanistic explanations yet for why some people accumulate fewer senescent cells as they age.

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