bioRxiv : the preprint server for biologyJun 22, 2026

Aging and reactive support brain cells show different gene patterns and functions

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 23, 2026

Abstract

Gene expression profiling reveals distinct profiles between senescent and reactive astrocytes.

Reactive astrocytes primarily express genes linked to inflammatory responses.
Senescent astrocytes show gene expression and secretion patterns that suggest involvement in synaptic pruning.
Functional analysis indicates that senescent astrocytes can support neurite outgrowth, unlike reactive astrocytes.
Senescent and reactive astrocytes may have different functional roles in the aging brain.
The inflammatory characteristics of both astrocyte types complicate their identification with current methods.

Simplified

Astrocytes assume multiple phenotypes in the brain in response to stress, injury, inflammation, and aging. Given the complexity of this critical cell type in the CNS, it is important to gain a greater understanding of the differences between these phenotypes and to potentially identify therapeutic approaches to modifying astrocyte function in the context of disease and aging. We compared senescent and reactive astrocytes using a strictly defined paradigm to induce these phenotypes in human astrocytes. Gene expression profiling reveals overlapping but distinct expression profiles. Reactive astrocytes predominantly express genes involved in inflammatory responses while senescent astrocytes express genes and a secretome that suggests a role in synaptic pruning. Unexpectedly, functional analysis in a simplified neurite outgrowth assay suggests that senescent astrocytes retain the ability to support neurite outgrowth while reactive astrocytes lose this capacity. The data suggests that senescent and reactive astrocytes play distinct functional roles in the physiology of the aging brain. However, the overlapping inflammatory nature of senescent and reactive astrocytes makes it difficult to discriminate between them using existing toolsets designed to identify senescent cells.