| First Author | North BJ | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 13 | Pages | 1438-53 |
| PubMed ID | 24825348 | Mgi Jnum | J:211655 |
| Mgi Id | MGI:5575817 | Doi | 10.15252/embj.201386907 |
| Citation | North BJ, et al. (2014) SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J 33(13):1438-53 |
| abstractText | Mice overexpressing the mitotic checkpoint kinase gene BubR1 live longer, whereas mice hypomorphic for BubR1 (BubR1(H/H)) live shorter and show signs of accelerated aging. As wild-type mice age, BubR1 levels decline in many tissues, a process that is proposed to underlie normal aging and age-related diseases. Understanding why BubR1 declines with age and how to slow this process is therefore of considerable interest. The sirtuins (SIRT1-7) are a family of NAD(+)-dependent deacetylases that can delay age-related diseases. Here, we show that the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP. Overexpression of SIRT2 or treatment of mice with the NAD(+) precursor nicotinamide mononucleotide (NMN) increases BubR1 abundance in vivo. Overexpression of SIRT2 in BubR1(H/H) animals increases median lifespan, with a greater effect in male mice. Together, these data indicate that further exploration of the potential of SIRT2 and NAD(+) to delay diseases of aging in mammals is warranted. |
