Klotho Argued to Reduce Glial Cell Inflammation

Why does increased klotho expression extend life in mammals? While evidence shows klotho to improve cognitive function, it is also thought to largely function in the kidneys, and thus effects on brain aging are indirect. The research noted here challenges that, though it is conducted on cells in culture, not in living animals. The researchers suggest that klotho will reduce age-related inflammation in brain tissue by suppressing the inflammatory response of glial cells. Reduced inflammation will in turn slow brain aging and loss of cognitive function. Whether this in vitro behavior will hold up in vivo remains to be established; there continues to be some debate as to whether klotho is meaningfully active in the brain in the context of aging.

Glia are non-neuronal cells of the brain and nervous system. There are several subtypes of glial cells, including astrocytes, oligodendrocytes, and microglia. A new study involved in vitro experiments using a lipopolysaccharide (LPS) to induce inflammation in cultured glial cells. Lipopolysaccharides are components of Gram-negative bacteria cell walls that can cause an acute inflammatory response by triggering the release of pro-inflammatory cytokines in various cell types, potentially leading to cell death.

The researchers set out to see whether pre-treatment with klotho could protect glial cells against the surge in levels of pro-inflammatory mediators after the administration of LPS. The results showed for the first time in cultured neural cells that klotho can indeed have anti-inflammatory and neuroprotective effects. Klotho not only acts on the metabolic coupling between neurons and astrocytes but is also an important player in modulating glia neuroinflammation. 

Link: https://agencia.fapesp.br/protein-with-anti-aging-action-combats-inflammation-and-avoids-death-of-neurons/40586/

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