Researchers at Karolinska Institutet have discovered that the nervous system's own immune cells help protect the spinal cord from age-related damage. The results, which may contribute to new knowledge about how certain neurological diseases arise, are published in the journal Nature Neuroscience.
Ageing affects the entire body, including the spinal cord, which transmits signals between the brain and the rest of the body. The negative consequences of ageing are well known, but could there be positive, protective mechanisms activated?
The researchers at Karolinska Institutet investigated how ageing affects myelin, the protective layer which envelops nerve fibres in the brain and spinal cord. By studying mice of different ages, the researchers found that the myelin in a specific region of the spinal cord – the dorsal columns – gradually accumulates damage during ageing.
The researchers focused on the immune cells of the brain and spinal cord, microglia, which help to keep the nervous system functioning properly.
"It is known that microglia can affect the quality of myelin, so we wanted to understand how these cells respond to age-related myelin damage," says Harald Lund, Assistant Professor at the Department of Physiology and Pharmacology at Karolinska Institutet.
In the ageing spinal cord, the researchers discovered that the microglia activated a signalling molecule called TGF-beta. This appears to act as a brake, preventing the cells from becoming overactive and damaging nerve fibres.
To test the significance of this brake, the researchers switched off TGF-beta production in older mice. Without the signal, the microglia began to attack the myelin, resulting in the mice developing clinical movement problems.
"Damage has also been found in this particular region of the spinal cord in people with certain neurological diseases. Our results may help us understand why," says Robert Harris, Professor at the Department of Clinical Neuroscience at Karolinska Institutet, who led the research together with Harald Lund.
The study was conducted in collaboration with researchers in China, the United States, and France. Funding was provided by the Swedish Research Council, Alltid Litt Sterkere, Neurofonden and Karolinska Institutet's research initiative StratNeuro, among others. The researchers report no conflicts of interest.
Publication: " TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration " Keying Zhu, Yun Liu, Jin-Hong Min, Vijay Joshua, Jianing Lin, Yue Li, Judith C. Kreutzmann, Yuxi Guo, Wenlong Xia, Elyas Mohammadi, Melanie Pieber, Valerie Suerth, Yiming Xia, Zaneta, Andrusivova, Jean-Philippe Hugnot, Shigeaki Kanatani, Per Uhlén, Joakim Lundeberg, Xiaofei Li, Stephen P.J. Fancy, Heela Sarlus, Robert A. Harris, Harald Lund, Nature Neuroscience, online 2 January 2026, doi: 10.1038/s41593-025-02161-4.
