The Glymphatic System and Waste Clearance with Brain Aging: A Review

Gerontology. 2019;65(2):106-119. doi: 10.1159/000490349. Epub 2018 Jul 11.


The glymphatic system is a glial-dependent waste clearance pathway in the brain, in place of lymphatic vessels, dedicated to drain away soluble waste proteins and metabolic products. Specifically, the glymphatic network serves as a "front end" for waste clearance, and is connected downstream to an authentic lymphatic network, associated with dura covering the brain as well as cranial nerves and large vessels at the skull exits. The anatomical and functional interconnections between these two networks are not completely understood. Several key physiological processes have been identified that control glymphatic transport function and waste clearance from brain. In this review, we aim to provide an overview and discussion of the concept behind the glymphatic system, current evidence, and controversies, while specifically focusing on the consequences of aging and evidence of its existence in human brain. Discovering novel strategies for optimizing and maintaining efficient brain waste clearance across the lifespan may in the future prove to be important for preventing cognitive decline and sustaining healthy aging.

Keywords: AQP4; Aging; Cerebrospinal fluid transport; Glymphatic; Human brain; Perivascular space; Pulsatility; Sleep; Waste solutes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging* / pathology
  • Aging* / physiology
  • Animals
  • Brain* / anatomy & histology
  • Brain* / physiology
  • Brain* / physiopathology
  • Glymphatic System* / anatomy & histology
  • Glymphatic System* / physiology
  • Humans