Cellular Senescence Is a Central Driver of Cognitive Disparities in Aging.

Matthew P Baier, Rojina Ranjit, Daniel B Owen, Jenna L Wilson, Megan A Stiles, Anthony M Masingale, Zachary Thomas, Anne Bredegaard, David M Sherry, Sreemathi Logan

Department of Biochemistry and Physiology, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, USA.Department of Biochemistry and Physiology, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, USA. · pubmed

Paper

Abstract

Cognitive function in aging is heterogeneous: while some older individuals develop significant impairments and dementia, others remain resilient and retain cognitive function throughout their lifespan. The molecular mechanisms that underlie these divergent cognitive trajectories, however, remain largely unresolved. Here, we utilized a high-resolution home-cage-based cognitive testing paradigm to delineate mechanisms that contribute to age-related cognitive heterogeneity. We cognitively stratified aged C57Bl/6N male mice by cognitive performance into intact (resilient) or impaired subgroups based on young performance benchmarks. Cognitively impaired males exhibited marked reactive gliosis in the hippocampus, characterized by microglial activation, increased astrocyte arborization, and elevated transcriptional expression of reactivity markers. These changes were accompanied by increased markers of cellular senescence and the associated senescence-associated secretory phenotype (SASP) in impaired animals, including p16

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

Cellular senescence contributes to cognitive disparities in aging by affecting neuroinflammatory responses in the brain. The study addresses the underlying mechanisms of cognitive decline in aging, which is pertinent to understanding and potentially mitigating age-related cognitive impairments.

Author of this paper? Send a correction.