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CEREBRAL FUNCTIONS: the crucial role of sirtuins in aging.

Aging

Various cellular and molecular changes occur in brain constituents (e.g. neurons, microglia, astrocytes and oligodendrocytes) during the aging process, affecting cerebral functions. In mammals, recent studies have shown that the brain, the hypothalamus in particular, is a key bidirectional integrator of humoral and neural information from peripheral tissues, thus influencing ageing both in the brain and ‘systemically‘.

Functional alterations, such as cognitive decline, mental deficits, sleep disruption and circadian dysfunction, are induced by these cellular and molecular changes. Sirtuins play crucial roles in the regulation of cerebral functions during the aging process.

Microglia activation, probably caused by reduced sirtuin activity, induces prolonged neuroinflammation, resulting in synaptic damage and neuronal death. This research in Nature explores how age-associated decline in cerebral functions, particularly hypothalamic function, which is likely due to reduced SIRT1 activity, mediates ageing at the systemic level and ultimately affects longevity in mammals.

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