# The Influence of Interleukin 6 Knockout on Age-Related Degenerative Changes in the Cerebellar Cortex of Mice

## TL;DR

This study shows that removing IL-6 in mice reduces age-related brain cell damage in the cerebellum, suggesting IL-6 plays a harmful role in aging.

## Contribution

The study reveals that IL-6 deficiency mitigates age-related Purkinje cell degeneration through reduced p53 stress and inflammation.

## Key findings

- IL-6 knockout mice showed less Purkinje cell degeneration and mitochondrial damage compared to wild-type mice at 24 months.
- Reduced p53 expression and neuroinflammation in IL-6KO mice correlated with improved neuronal survival.
- Apoptosis played a minimal role in Purkinje cell loss, as indicated by low levels of apoptotic markers.

## Abstract

This study investigates age-related neurodegeneration in the cerebellar cortex, emphasizing the role of IL-6 deficiency in preserving Purkinje cells. We found that apoptosis plays a minimal role in Purkinje cell loss by using 4-month- and 24-month-old wild-type (WT) and IL-6 knockout (IL-6KO) mice. At 24 months, WT mice exhibited severe Purkinje cell degeneration, including atrophic cell bodies, eosinophilic cytoplasm, pyknotic nuclei, mitochondrial disruption, and increased levels of lipofuscin-rich lysosomes. In contrast, IL-6KO mice showed fewer lysosomes, reduced mitochondrial damage, and less neuronal atrophy, indicating a neuroprotective effect. Lower p53 expression and decreased levels of its downstream effectors (p21, and Bax) in IL-6KO mice correlated with reduced cellular stress. Minimal changes in apoptotic markers (Bax and caspase-3) further reinforce the limited role of apoptosis. Neuroinflammation, marked by elevated GFAP, was prominent in aged WT mice but attenuated in IL-6KO mice. Reduced p53 accumulation, less severe neuroinflammation, and preserved metabolic homeostasis in IL-6KO mice correlated with improved Purkinje cell survival. These findings suggest that IL-6 accelerates neurodegeneration via p53-associated stress and inflammation, while IL-6 deficiency mitigates these effects. Targeting IL-6 signaling through anti-inflammatory strategies or IL-6 inhibition may offer a therapeutic approach for age-related neurodegenerative disorders.