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Today, we want to draw your attention to a new study that looks at the role of chronic age-related inflammation and the decline of nerve regeneration.

Inflammaging drives age-related loss of tissue regeneration

Inflammation can be beneficial and serves an important purpose: it spurs regeneration and immune responses while combating pathogens and other invaders. This kind of inflammation tends to be short-lived and localized to an area of injury. However, there is another form of inflammation, a chronic, smouldering kind that accompanies aging: this is often called inflammaging.

This backdrop of low-grade inflammation contributes significantly to mortality risk in the elderly and has a number of sources, including senescent cells, cell debris, microbial burden, and immunosenescence. Inflammaging is believed to be a significant risk factor for a variety of age-related diseases, including atherosclerosis, arthritis, hypertension, and cancer [1-3].

When the inflammation level is constant, as it is in inflammaging, it prevents stem cells from functioning properly and inhibits tissue repair and regeneration; this is one reason why we heal injuries slower as we age.

A new study further confirms the debilitating role of chronic, age-related inflammation in the loss of tissue regeneration [4]. The authors show that CC chemokine ligand 11 (CCL11) interferes with the regeneration of nerve cells by altering cell behaviour, and they suggest that anti-inflammatory therapies may be a useful approach to boosting nerve regeneration in the elderly.

Abstract

The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.

Conclusion

The effective management of out-of-control age-related inflammation is a promising strategy in improving tissue repair and regeneration in the elderly. Ultimately, removing the underlying sources of inflammaging would be the logical conclusion, and thus therapies such as senolytics, which purge the body of inflammatory senescent cells, offer the possibility of improving tissue regeneration simply by directly removing a major source of inflammation. Studies like this reinforce what we know about the role of chronic inflammation in aging and show that strategies that reduce this inflammation should be effective.

Literature

[1] Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med (2010) 16(5):238–46. doi: 10.1016/j.molmed.2010.03.003

[2] Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R. M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017). Senescent cells: an emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718.

[3] He, S., & Sharpless, N. E. (2017). Senescence in health and disease. Cell, 169(6), 1000-1011.

[4] Büttner, R., Schulz, A., Reuter, M., Akula, A. K., Mindos, T., Carlstedt, A., … & Morrison, H. (2018). Inflammaging impairs peripheral nerve maintenance and regeneration. Aging cell, e12833.

About the author

Steve Hill

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
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