Neuropeptide Y and brain ageing: an updated scoping review on the role of autophagy.

Brain ageing is a complex physiological process characterised by progressive structural and functional changes that often result in cognitive decline and reduced quality of life in the elderly. These changes are driven by multiple mechanisms, including synaptic dysfunction, oxidative stress, neuroinflammation, and impaired cellular homeostasis. Neuropeptides have emerged as important regulators of these processes. Among them, neuropeptide Y (NPY) has gained attention for its potential role in mitigating age-related brain dysfunction. However, the extent to which NPY contributes to brain ageing remains unclear. This scoping review aims to map the available evidence on the role of NPY in brain ageing, focusing on the effect of NPY on autophagy, a key mechanism involved in brain ageing. Scientific studies published between 2014 and 2026 relevant to the research topic were systematically screened and reviewed. Following a rigorous selection process, four articles that met the inclusion and exclusion criteria were included for analysis. The findings indicate that NPY levels decline in the hypothalamic arcuate nucleus in a progeroid mouse model, where restoring NPY delays several ageing phenotypes. In addition, NPY appears to mitigate brain ageing by promoting autophagy in the hypothalamus and cerebral cortex, an effect requiring both suppression of PI3K/AKT/mTOR signalling and activation of ERK1/2-MAPK. These insights may pave the way for future research into therapeutic strategies targeting NPY to combat age-related cognitive deficits and neurodegenerative diseases. However, further investigation is needed to elucidate the underlying mechanisms of NPY action, including the roles of its various receptors and interactions with other neuropeptides.