# Aging of neural stem cells and vascular dysfunction: mechanisms, interconnection, and therapeutic perspectives

## TL;DR

This paper explores how aging affects neural stem cells and blood vessels in the brain, and how these changes contribute to cognitive decline and brain diseases.

## Contribution

The paper highlights the interconnection between neural stem cell aging and vascular dysfunction, and proposes stem cell-based therapies as potential treatments.

## Key findings

- Aging reduces neurogenesis through declines in BDNF and VEGF pathways.
- Vascular issues worsen brain health by breaking down the blood-brain barrier and reducing blood flow.
- Stem cell therapies like MSCs and iPSCs may help repair age-related brain damage.

## Abstract

•Neural stem cell aging impairs neurogenesis via BDNF and VEGF pathway decline.•Vascular dysfunction promotes BBB breakdown and cerebral hypoperfusion.•Oxidative stress and inflammation drive neurovascular unit degeneration.•mTOR hyperactivation and AMPK suppression accelerate NSC senescence.•Stem cell-based approaches (MSC, iPSC) hold promise for neurovascular repair.

Neural stem cell aging impairs neurogenesis via BDNF and VEGF pathway decline.

Vascular dysfunction promotes BBB breakdown and cerebral hypoperfusion.

Oxidative stress and inflammation drive neurovascular unit degeneration.

mTOR hyperactivation and AMPK suppression accelerate NSC senescence.

Stem cell-based approaches (MSC, iPSC) hold promise for neurovascular repair.

Aging of the central nervous system is accompanied by a progressive decline in neuroplasticity, regenerative capacity, and vascular integrity. Neural stem cells (NSCs) and cerebral vasculature are both critically involved in maintaining homeostasis, and their age-related dysfunction contributes to neurodegenerative and cerebrovascular diseases.

This article explores the mechanisms underlying NSC aging and vascular deterioration, their mutual interconnection, and the implications for brain health in aging populations.

We review current evidence on molecular and cellular pathways affecting neurogenesis and cerebral perfusion, including dysregulation of BDNF, VEGF, mTOR, AMPK, and the effects of oxidative stress and chronic inflammation. We also highlight emerging biomarkers and therapeutic targets.

Aging disrupts the neurovascular unit, impairing both neurogenesis and vascular support systems. Chronic inflammation and oxidative stress exacerbate these processes, forming a self-perpetuating degenerative cycle. Antioxidant and anti-inflammatory therapies, along with stem cell–based interventions such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), show promise for restoring neural and vascular function.

Addressing both NSC and vascular aging is essential for developing effective interventions against cognitive decline and cerebrovascular pathology. Integrative and personalized therapeutic strategies targeting shared molecular pathways hold great promise for future clinical applications.