Schedule of Events | Search Abstracts | Invited Symposia | Symposia | Rising Stars | Poster Sessions | Data Blitz

DNA Repair and epigenetic regulation in mice overexpressing SIRT6 variants from long- and short-lived species

Poster Session A - Saturday, March 7, 2026, 3:00 – 5:00 pm PST, Fairview/Kitsilano Ballrooms

Mila Kaplan¹ (mkapl17@u.rochester.edu), Joseph Cutting, Andrei Seluanov, Vera Gorbunova; ¹University of Rochester

Sirtuin 6 (SIRT6), an NAD-dependent enzyme, regulates several of the hallmarks of aging, including genomic stability and epigenetic modifications. DNA damage repair plays a major role in genomic stability, and SIRT6 from longer-lived species has been shown to enhance DNA double-strand break (DSB) repair activity. SIRT6 overexpression in mice has been shown to significantly increase longevity. We isolated mouse, beaver, human, and bowhead whale SIRT6 variants and tested how overexpression of these variants in mice affects DNA DSB repair in response to oxidative stress. Following induction of oxidative stress with H2O2 treatment, there was a trend toward an increase in live cells in cells overexpressing beaver, human, and bowhead whale SIRT6 compared to controls, suggesting that the SIRT6 from beaver, humans, and bowhead whales may reduce apoptosis due to oxidative stress. Additionally, to understand why there are differences in DNA DSB repair activity, we investigated post-translational modifications via immunoblotting. SIRT6 from bowhead whale showed increased phosphorylation, which may be responsible for its enhanced DNA DSB repair activity. Lastly, we assessed the cognitive and locomotive differences in the mice to determine the effect of human and bowhead whale SIRT6 overexpression on the mice’s physical and mental ages via an open field test. Old human SIRT6-overexpressing male mice showed a trend of increased in-center frequency (a measure of decreased anxiety) compared to the older control mice, which demonstrates that human SIRT6 may be ameliorating the age-related anxiety in the mice.

Topic Area: EMOTION & SOCIAL: Development & aging