New mechanisms of aging: From vascular to neurological system

Aging is marked by progressive physiological decline, with vascular aging emerging as a pivotal contributor to chronic diseases, including cardiovascular disorders and neurological disorders. As emphasized by Thomas Sydenham’s axiom, “a man is as old as his arteries,” age-dependent arterial remodeling—characterized by endothelial dysfunction, oxidative stress, and arterial stiffening—compromises cerebral perfusion and blood-brain barrier integrity. These vascular alterations disrupt cerebral homeostasis, fostering hypoperfusion, microvascular damage, and neurotoxic inflammation, which synergize with amyloid-β and tau pathologies to accelerate cognitive decline. Understanding the processes of arterial aging is crucial, as numerous age-related cardiovascular and cerebrovascular diseases stem from alterations in arterial function or are exacerbated by functional and phenotypic changes in the arteries. Prioritizing vascular health in aging populations may thus offer a dual benefit: delaying arterial aging and preserving cognitive function, addressing one of the most urgent public health challenges of the 21st century. This review highlights the critical role of vascular aging in the pathophysiology of neurological disorders and discusses emerging therapeutic targets for their alleviation. • Vascular aging is a critical driver of neurological deterioration, as it disrupts cerebral perfusion and weakens blood–brain barrier integrity. Additionally, impaired neurovascular coupling and autonomic dysregulation further accelerate vascular decline, creating a vicious cycle of degeneration. • The vascular–neural axis is pivotal in aging, with the neurovascular unit undergoing a synchronized decline in both structural and functional aspects that undermines brain homeostasis. • Chronic inflammation and immunosenescence serve as key mediators bridging vascular impairment and neural degeneration, presenting a compelling therapeutic avenue