Chronic low-grade inflammation

This kicks off a series of posts on inflammation, specifically chronic low-grade inflammation (CLGI), a common condition that is not considered a disease but is likely the precursor of many, many diverse diseases: diabetes, obesity, liver disease, hypertension, atherosclerosis, cancer, degenerative brain diseases, and more, including, perhaps, some auto-immune diseases. Self-reinforcing feedback loops may dominate anti-inflammatory responses over time and aggravate the condition.

I should first briefly define CLGI: it refers to a sustained state of inflammation (activated immune cells that release “alert” molecules that further stimulate the immune system) in the body, where the inflammatory response is ongoing but at a lower intensity than acute, infection-related inflammation.

It should be noted that number of these diseases are also considered “diseases of aging” and, indeed, there is a hallmark of aging called “inflammaging”, which reflects an increase in CLGI prevalence with chronological age. The figure below is from an excellent article that clearly shows a network of (mostly) mutually reinforcing hallmarks, not a clear one-directional causal graph: “Chronic inflammation and the hallmarks of aging”, Jordan J. Baechle, Nan Chen, Priya Makhijani, Shawn Winer, David Furman, Daniel A. Winer, Molecular Metabolism, Volume 74, 2023, 101755.

But CLGI can begin early: it is just that certain correlates of age seem to make it more frequent.

What I find fascinating is that the interventions that will lower or alleviate CLGI overlap almost perfectly with the “modifiable risk factors” described in the BMJ Journal of Neurology, Neurosurgery & Psychiatry article, “Modifiable risk factors for stroke, dementia and late-life depression: a systematic review and DALY-weighted risk factors for a composite outcome” (link below). The authors noted that “60% of stroke, 40% of dementia and 35% of late-life depression (LLD) are attributable to modifiable risk factors, with great overlap due to shared pathophysiology.” Their TL;DR? Keep your blood pressure under control, engage in regular intellectual as well as physical activity, rein in your blood glucose and weight, don’t smoke, don’t drink, avoid stress (ha!), get quality sleep, be a pescatarian, take care of your kidneys by minimizing processed food and salt, have a purpose in life and enjoy a vigorous social life. Do that and your probability of suffering from any of these diseases of old age collapses.

There is some emerging, mostly observational, evidence about the effects of purpose and social life on inflammation, but for the rest, the same interventions that decrease your chances of stroke, dementia or late-life depression are the same that decrease CLGI. And given that CLGI is a precursor to a lot of these conditions, maybe it should be considered worth treating.

Jordan Shlain, MD, David Barzilai MD PhD MBA MS DipABLM, Eric Verdin, Nan Chen, Priya Makhijani, Shawn Winer, David Furman, Daniel A. Winer

Chronic inflammation and the hallmarks of aging : https://doi.org/10.1016/j.molmet.2023.101755

Modifiable risk factors for stroke, dementia and late-life depression: a systematic review and DALY-weighted risk factors for a composite outcome : paywalled article: link MedRxiv preprint: https://lnkd.in/eh44xRzC)