Blocking SIRT1 inhibits cell proliferation and promotes aging through the PI3K/AKT pathway

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Abstract

Aims:

Alzheimer's disease (AD) is the most prevalent age-related disease and the most common cause of dementia in the elderly. Its hallmark neuropathological features are the presence of amyloid-beta oligomers and neurofibrillary tangles that are composed of hyperphosphorylated tau protein. SIRT1 has been shown to have a neuroprotective effect; however, its working mechanisms are not well understood. This study aimed to address this issue.

Main methods:

We used an in vitro neuronal SH-SY5Y cell culture model to investigate the effect of SIRT1 knockdown on cell survival, proliferation, functionality, and cytotoxicity. We also investigated how SIRT1 knockdown affected relevant signaling/regulator molecules, including AKT, CREB, and p53, to gain further mechanistic insight.

Key findings:

We found that SIRT1 knockdown inhibited cell survival, proliferation, and functionality. These effects were associated with suppressed AKT activity and CREB activation and increased p53 expression.

Significance:

These results will help us to better understand the protective role of SIRT1 in AD, and they support the potential use of SIRT1 as a biomarker and drug target for the prevention, diagnosis, and treatment of AD as well as other relevant age-related diseases.

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