This study examines the critical role of collagen VI in the central nervous system and its impact on neurodegeneration during aging. Using a collagen VI null mouse model (Col6a1–/–), researchers explored the effects of collagen VI deficiency on neural cells both in vitro and in vivo. The findings underscore the protective role of collagen VI in neuronal survival and its potential as a therapeutic target for age-related neurodegenerative diseases.

In vitro experiments revealed that neural cells from collagen VI deficient mice exhibited higher rates of spontaneous apoptosis, indicating that collagen VI plays a crucial role in preventing neuronal cell death. Additionally, the absence of collagen VI disrupted autophagy, a vital cellular process for recycling and degrading cellular components. These defects highlight collagen VI's importance in maintaining cellular homeostasis in the brain.

In vivo studies supported these findings, showing increased apoptosis in the brains of newborn and aged Col6a1–/– mice. Aged collagen VI deficient mice also exhibited elevated levels of reactive oxygen species (ROS), a marker of oxidative stress. These cellular defects translated into functional impairments, as behavioral tests on aged Col6a1–/– mice demonstrated significant deficits in motor coordination and spatial memory compared to wild-type mice.

By combining various experimental approaches, including neural cell cultures, protein analyses, and behavioral assessments, the study provided a comprehensive understanding of collagen VI's role in the brain. The results emphasize its protective functions against cellular stress and degeneration, highlighting its potential as a therapeutic target for mitigating age-related cognitive decline and neurodegenerative conditions.