Advances in the study of the glymphatic system and aging

CNS Neurosci Ther. 2024 Jun;30(6):e14803. doi: 10.1111/cns.14803.

Abstract

The glymphatic system is cerebrospinal fluid-brain tissue fluid exchange flow mediated by aquaporin-4 (AQP4) on the end feet of astrocytes for a system, which is capable of rapidly removing brain metabolites and thus maintaining brain homeostasis, and is known as the central immune system. Dysfunction of the glymphatic system causes accumulation of misfolded and highly phosphorylated proteins (amyloid-β and Tau proteins), which destabilizes the proteins, and the body's neuroinflammatory factors are altered causing aging of the immune system and leading to neurodegenerative diseases. Damage to the glymphatic system and aging share common manifestations, as well as unstudied biological mechanisms that are also linked, such as mitochondria, oxidative stress, chronic inflammation, and sleep. In this paper, we first summarize the structure, function, and research methods of the glymphatic system and the relationship between the glymphatic system and the peripheral immune system, and second, sort out and summarize the factors of the glymphatic system in removing metabolites and resolving aging-related diseases and factors affecting aging, to explore its related biological mechanisms, and moreover, to provide a new way of thinking for treating or intervening aging-related diseases.

Keywords: aging; glymphatic system; immunosenescence; neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Aging* / metabolism
  • Aging* / physiology
  • Animals
  • Aquaporin 4 / metabolism
  • Astrocytes / metabolism
  • Brain / metabolism
  • Glymphatic System* / metabolism
  • Glymphatic System* / physiology
  • Humans

Substances

  • Aquaporin 4