Addressing the knowledge gap in spinal cord aging, researchers from the Institute of Zoology and the Beijing Institute of Genomics of the Chinese Academy of Sciences have made an original discovery. Their study, published in Nature on Oct. 31, revealed a previously unknown subtype of CHIT1 (a secreted mammalian chitinase)-positive microglia in the aged spinal cord of non-human primates.

These cells, which they named Aging-Induced Motor Neuron toxic CHIT1-Positive Microglia (AIMoN-CPM), play a driving role in motor neuron aging by activating SMAD signaling through the secretion of the CHIT1 protein.

The spinal cord, a vital bridge between the brain and peripheral nerves, plays a pivotal role in controlling motor functions and coordinating basic life activities of the body, primarily through a rare and critical group of cells within the spinal cord called motor neurons.

As the "command center" for human movement and basic organ autonomoy, the aging process of the spinal cord has significant implications for the coexistence of various chronic diseases in the elderly population. However, the mechanisms of spinal cord aging remain poorly understood.

Metaphorically speaking, microglia function like security guards in the spinal cord. But with age, some of them become overly vigilant, accelerating the aging process of motor neurons. Promisingly, the researchers showed that blocking the CHIT1-SMAD signaling pathway or supplementing with vitamin C can counteract the pro-aging effects of this "overzealous security" on spinal cord motor neurons.

In addition, elevated levels of CHIT1 have been observed in both the cerebrospinal fluid and blood of older individuals compared to younger individuals. This fluid-based biomarker has the potential to assess the degree of spinal cord aging.

"This study provides the first systematic characterization of the phenotypic, pathological, cellular and molecular features of primate spinal cord aging, deepening our understanding of human spinal cord degeneration," said Prof. LIU Guanghui, the principal investigator of the study. "By targeting AIMoN-CPM and CHIT1 signaling, we hold promise for slowing down spinal cord aging and treating age-related comorbidities."

This work sheds light on the intricate mechanisms underlying spinal cord aging and provides hope for the development of interventions to mitigate its effects. As the aging population continues to grow, this study paves the way for potential strategies to improve quality of life and manage age-related health challenges. 

Panoramic view of primate spinal cord aging (Image by SUN Shuhui)