- A deficiency in the DNA repair factor ERCC1 accelerates aging phenotypes and generates gene expression profiles reminiscent of aged animals (Niedernhofer et al., 2006)
- Deletion of another Sir2 homolog, SIRT6, reduces base excision DNA repair and causes an accelerated aging phenotype in mice (Mostoslavsky et al., 2006)
- Additional SIR2 suppresses the toxicity, genomic instability, and desilencing caused by genotoxic stress
- In yeast, the recruitment of Sir proteins to a DNA double-strand break (DSB) requires DNA damage signaling through MEC1, an ortholog of the mammalian PI3-kinases ATR/ATM
- Increased SIRT1 Levels Protect from Irradiation-Induced Cancer in Mice
- SIRT1 Is Required for Efficient DSB Repair and Genomic Stability
- a recent report showed that SIRT1 recruitment to a DNA break in CpG islands can result in DNA methylation changes and heritable gene silencing
- increased SIRT1 expression can suppress genomic instability and gene expression alterations, perhaps CR promotes genomic stability and delays aging in mammals via a similar mechanism
- pathways that control lifespan in mammals: IGF-1, TSC, mTOR, sirtuins
- Mice overexpressing the mitotic checkpoint kinase gene BubR1 live longer, whereas mice hypomorphic for BubR1 (BubR1H/H) live shorter and show signs of accelerated aging