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Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research Laboratory animalsC57Bl/6 male mice, aged (19 months from NIA rodent colony), young (3 months from Charles River or Jackson Labs) Wild animalsThis study did not involve wild animals.Field-collected samples This study did not involve field-collected samples. Ethics oversightInstitutional Animal Care and Use Committee at Stanford University Note that full information on the approval of the study protocol must also be provided in the manuscript. Human research participantsPolicy information about studies involving human research participants Population characteristicsMale and female aged (58-93 years old) cognitively normal and clinically-diagnosed Alzheimer's disease patients. Cognitively normal patients do not display atypical vascular pathologies. Patients are mixed in APOE genotype. RecruitmentSubjects were not recruited specifically for this study. Samples are derived from a brain bank maintained by the Stanford/ VA/ NIA Aging Clinical Research Center (ACRC) from patients that provide consent for broad, de-identified data sharing under Institutional Review Board (IRB) approval. Ethics oversightStanford/ VA/ NIA Aging Clinical Research Center (ACRC) Note that full information on the approval of the study protocol must also be provided in the manuscript.

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Sirtuins are evolutionarily conserved proteins that use nicotinamide adenine dinucleotide (NAD+) as a co-substrate in their enzymatic reactions. There are seven proteins (SIRT1-7) in the human sirtuin family, among which SIRT1 is the most conserved and characterized. SIRT1 in the brain, in particular, within the hypothalamus, plays crucial roles in regulating systemic energy homeostasis and circadian rhythm. Apart from this, SIRT1 has also been found to mediate beneficial effects in neurological diseases. In this review, we will first summarize how SIRT1 in the brain relates to obesity, type 2 diabetes, and circadian synchronization, and then we discuss the neuroprotective roles of brain SIRT1 in the context of cerebral ischemia and neurodegenerative disorders.