binding sites of the PARP1 promoter are epigenetically hypomethylated, PARP1 is expressed at an elevated level. Cells from older humans (69 to 75 years of age) have a constitutive expression level of both PARP1 and PARP2 genes reduced by half, compared to their levels in young adult humans (19 to 26 years old). However, centenarians (humans aged 100 to 107 years of age) have constitutive expression of PARP1 at levels similar to those of young individuals. This high level of PARP1 expression in centenarians was shown to allow more efficient repair of H2O2 sublethal oxidative DNA damage. Higher DNA repair is thought to contribute to longevity (see DNA damage theory of aging). The high constitutive levels of PARP1 in centenarians were thought to be due to altered epigenetic control of PARP1 expression. Both sirtuin 1 and PARP1 have a roughly equal affinity for the NAD+ that both enzymes require for activity. But DNA damage can increase levels of PARP1 more than 100-fold, leaving little NAD+ for SIRT1. Role in cell death Following severe DNA damage, excessive activation of PARP1 can lead to cell death. Initially, overactivation of the enzyme was linked to apoptotic cell death but later, PARP1-mediated cell death turned out to show characteristics of necrotic cell death (i.e. early plasma membrane disruption, structural and functional mitochondrial alterations). These findings provided explanation for previous and subsequent reports demonstrating tissue protective effects of PARP inhibitors and the PARP1 knockout phenotypes in various models of ischemia-reperfusion injury (e.g. in stroke, in the heart and in the gut) where oxidative stress-induced cell death is a central cellular event. Later, apoptosis inducing factor (AIF; a misnomer) was identified as a key mediator of the PARP1-mediated regulated necrotic cell death pathway termed parthanatos. Plant PARP1 Plants have a PARP1 with substantial similarity to animal PARP1, and roles of poly(ADP-ribosyl)ation in plant responses to DNA damage, infection and other stresses have been studied. Intriguingly, in Arabidopsis thaliana (and presumably other plants), PARP2 plays more significant roles than PARP1 in protective responses to DNA damage and bacterial pathogenesis. The plant PARP2 carries PARP regulatory and catalytic domains with only intermediate similarity to PARP1, and carries N-terminal SAP DNA binding motifs rather than the Zn-finger DNA binding motifs of plant and animal PARP1 proteins. Interactions PARP1 has been shown to interact with: APTX MYBL2 RELA P53 POLA1 POLA2 XRCC1 ZNF423 See also DNA damage theory of aging