Inflammaging & Fountain of Youth?

“Inflammaging” is a 21st century term, describing a concept that chronic low-grade inflammation might be involved in whatever ails an aging person, from joint or skin problems to cognitive issues. If inflammaging is truly the root cause of so many problems, could finding a solution provide magic waters for the  Fountain of Youth?

Inflammation itself is a medical concept that goes back centuries, one of the cardinal observations about disease.  The physician Galen in the 3rd century named five components that AlzGadfly learned in the 20th century: pain, redness, heat, swelling and loss of function  (Latin dolor, rubor, calor, tumor, functio laesa).  It’s a defense and healing reaction that humans elaborate for many injuries or infections.

More recently, some are calling brain inflammation “central” to the neurodegeneration seen in Alzheimer’s and other dementias (Kinney et al 2018, review in Alzheimer’s & Dementia).  The authors are calling inflammation a third core pathology, along with amyloid plaques and tau tangles.  Separately, Franceschi evidently coined “inflammaging” a few decades ago; his more recent 2018 article appears in Nature Reviews.

These concepts are different from the acute inflammation that intern AlzGadfly saw long ago, in dozens of patients with bacterial meningitis, encephalitis and sepsis. So this is not your grandpa’s idea of inflammation, where the damage is overt at the tissue level; it’s based on molecular inflammatory markers.  Brain microglia may be the action cells in neurodegeneration, whereas nutrition and gut flora are important in inflammaging. The reviews are not explicit about correlations of direct action or damage.  The evidence seems circumstantial if one holds to pathology based criteria for inflammation.

This blog is about dementia and therapies, so before you go gobbling so-called “anti-inflammatory” OTC supplements and foods or NSAID medicines like ibuprofen, naproxen or aspirin, you should know that there have been dozens of negative dementia studies using those interventions.  Three useful databases are the Cochrane Library (medical meta-analyses), the Alz Drug Discovery Foundation / Cognitive Discovery Reports and the AlzForum Therapeutics DB.

In a related development, there is a category of meds known as “senolytics,” and there may be a bit of a positive indirect result this year.  A commentary in a Lancet journal describes a non-controlled Mayo pilot clinical trial in a severe lung disease using dasatinib and quercetin over only three weeks. Dasatinib is a chemotherapy agent and quercetin is claimed to have various “anti-” properties.  The Mayo pilot had 14 patients; their measurable lung function did not improve, but most could walk better. 

There is a senolytics trial listed for dementia, and it was mentioned at the Alz Assn Int’l Conf [AAIC20] this summer, by Dr. H. Fillit.  These seem like empiric repurposing trials, and this blog has praised the bold idea of performing empiric trials, which is part of the history for cancer therapeutics.

Maybe Ponce de Leon’s search for the Fountain of Youth was a myth, or once he got to St. Augustine, FL, he didn’t have the required coins for entry. Let’s hope all this research work yields therapeutic results, especially in the dementia arena.