TNFα Contributes to Age-Related Liver and Intestinal Barrier Dysfunction
A sizable fraction of degenerative aging involves chronic inflammation. Various forms of cell and tissue damage trigger maladaptive inflammatory signaling, such as the presence of lingering senescent cells and DNA released into the cytoplasm by dysfunctional mitochondria. Sustained inflammatory signaling changes cell behavior for the worse and is disruptive to tissue structure and function. Many of the important mediators of inflammatory signaling are well known, such as TNFα, but inhibiting these signals is a blunt tool that causes unwanted side effects, such as loss of necessary immune function and impaired long-term health.
Tumor necrosis factor α (TNFα) regulates inflammation in metabolic diseases and probably aging-associated inflammation. Here, TNFα´s role in aging-related liver inflammation and fibrosis and underlying mechanisms was assessed in mice. In male C57BL/6J mice, aging increased hepatic inflammation, senescence markers p16 and p21 and Tnfa mRNA expression in liver tissue. In a second study, 4 and 24-month-old TNFα knockout and wild-type (WT) mice were compared for senescence, liver damage, intestinal barrier function, and microbiota composition. 24-month-old TNFα knockout mice were significantly protected from the aging-associated increase in hepatic senescence, inflammation and fibrosis found in WT mice.
This protection was related with preserved stem cell marker expression, maintained small intestinal barrier function and lower bacterial endotoxin in portal blood. While differing from young mice, intestinal microbiota composition of old TNFα knockout mice differed markedly from age-matched WT mice. Also, TNFα was found to alter permeability and tight junction protein levels being reversed by the presence of an JNK inhibitor in an ex vivo intestinal tissue model. Taken together, our results suggest that TNFα plays a key role in the development of aging-related liver decline in male mice.
Much is said about chronic inflammation of aging. But I have never seen a word about how this is measured and what values are good, just OK and bad. Is High Sensitivity C-reactive protien the best test for this? What about regular CRP tests?
Please include this info in the next article that mentions inflammaging.
Thanks for all you do, Reason.
@Dean: there isn't really a simple answer. No one measure is good on its own, and all are situational to some degree. Combinations of a few different measures can be effective over a population, such as a combination of C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa). But various different studies tend to look at various different combinations of a great many more signal molecules, and any given individual may or may not reflect the average.