The Skin–brain Axis in Cutaneous Aging: Neurobiological Foundations and Clinical Implications

The skin– brain axis is a bidirectional neuroimmunoendocrine axis connecting psychological stress, brain signaling, immune responses, and skin homeostasis. A hypothetical link between dysregulation of this network and skin ageing is neurogenic inflammation, oxidative stress, cellular senescence, inflammaging, and activation of the hypothalamic–pituitary–adrenal axis. This dysregulation is increasingly recognized as associated with mechanisms of skin ageing, including neurogenic inflammation, oxidative stress, cellular ageing, inflammaging, and activation of the hypothalamic–pituitary–adrenal axis. This review focuses on the neurobiological mechanisms underlying cutaneous ageing and emphasizes the role of neurocutaneous receptors, neurotransmitters, neuropeptides, and neuro-signaling pathways in the stress response. It also examines emerging trends, such as 'neurocosmetics' including peptides that act on neurocutaneous pathways to stimulate regeneration, stress-modulating peptides, and myorelaxant peptides. This review provides new insight into the skin–brain axis as a potential model for better understanding stress-related skin ageing by combining intrinsic and extrinsic skin ageing with neurobiology. There are a variety of neuroactive cosmetic strategies, with some having mechanistic and preliminary clinical evidence, while others do not and require controlled, randomized studies with objective markers. Future preventive and therapeutic strategies to regulate neuroimmune and neuroendocrine signaling to preserve skin homeostasis and reduce stress-induced skin ageing may be available.