Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Wenyan Zhang; Hong-Shuo Sun; Xiaoying Wang; Aaron S Dumont; Qiang Liu

doi:10.1016/j.tins.2024.04.003

Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Trends Neurosci. 2024 May 9:S0166-2236(24)00061-4. doi: 10.1016/j.tins.2024.04.003. Online ahead of print.

Authors

Wenyan Zhang¹, Hong-Shuo Sun², Xiaoying Wang³, Aaron S Dumont³, Qiang Liu⁴

Affiliations

¹ Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Tianjin Medical University General Hospital, Tianjin 300052, China.
² Department of Physiology, University of Toronto, Toronto, ON, Canada.
³ Tulane Center for Clinical Neurosciences, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, USA.
⁴ Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: qliu@tmu.edu.cn.

PMID: 38729785
DOI: 10.1016/j.tins.2024.04.003

Abstract

Aging may lead to low-level chronic inflammation that increases the susceptibility to age-related conditions, including memory impairment and progressive loss of brain volume. As brain health is essential to promoting healthspan and lifespan, it is vital to understand age-related changes in the immune system and central nervous system (CNS) that drive normal brain aging. However, the relative importance, mechanistic interrelationships, and hierarchical order of such changes and their impact on normal brain aging remain to be clarified. Here, we synthesize accumulating evidence that age-related DNA damage and cellular senescence in the immune system and CNS contribute to the escalation of neuroinflammation and cognitive decline during normal brain aging. Targeting cellular senescence and immune modulation may provide a logical rationale for developing new treatment options to restore immune homeostasis and counteract age-related brain dysfunction and diseases.

Keywords: brain aging; brain barriers; immunity; neurodegeneration; neuroinflammation.

Publication types

Review