P2‐094: Sirtuin expression during aging and in Alzheimer's disease

Sirtuins are a class of histone deacetylases which have been shown to regulate a range of physiopathological processes such as cellular aging, inflammation, metabolism and cell proliferation. Although there are seven mammalian sirtuins (SIRT1-7), more detail is known about the function, distribution and substrate of the SIRT1 compared to the remaining sirtuins. Numerous studies have reported changes in SIRT1 in neurodegenerative diseases such as Alzheimer's disease (AD). Since aging is the biggest risk factor in the development of AD, we investigated changes in sirtuin levels in these conditions. We tested mRNA and protein expression levels levels in post-mortem human control and AD brain tissue (Hippocampus, Frontal, Occipital and Temporal lobes) using western blotting and real time PCR. To confirm whether these changes are due to Alzheimer's disease pathology or a response to aging, we characterised the changes in sirtuin expression in normal aged wistar rats. We found a significant increase in SIRT2 mRNA and protein expression in the occipital lobe. Our data also shows that SIRT5 is downregulated in the temporal lobe. From our results it seems that SIRT2 is the most abundant sirtuin in the human brain. In the aged female wistar rat brain, we found a significant upregulation in SIRT1, SIRT3, SIRT4, mRNA and protein expression in the frontal lobe, while SIRT2 is upregulated in the occipital lobe consistent with AD. SIRT5 and SIRT6 levels are reduced in the aging hippocampus, and temporal lobe, while SIRT7 was significantly increased in the temporal lobe. This study suggests that aberrant expression levels of sirtuins is present in AD and aging, and may represent metabolic differences between humans and rodents.