November 15th, 2021

What do we really know about aging?

We know that it accelerates under chronic unremitting stress of varied sources. Including - chronic high fat and sugar laden westernized diets, chronic chemical or drug exposure or acute if a toxic load, chronic sedentary behavior, chronic metal sadness or abuse, physical abuse, injury that is profound and much more.

It is no wonder looking at that list that we are aging poorly now despite high quality medical interventions that keep us alive.

Thus, what is our biological clock say about our age versus the chronological clock of age. Think of this as how old do you appear biologically or cellularly versus how old you really are by days.

From the Nature Aging article: "While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8–96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes." (Sayed et. al. 2021)

This group is using artificial intelligence to complete heroic data tasks to get us closer to understanding immune biology of biological aging that we see as heart disease or neurodegenerative disease. The chemokine CXCL9 is a major chemical signaling molecule involved in immune expansion in order to combat pathogens on a routine basis. It has recently been associated with MIS from COVID in children.

CXCL9 is antimicrobial gene that is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded is thought to be involved in T cell trafficking. The encoded protein binds to C-X-C motif chemokine 3 and is a chemoattractant for lymphocytes but not for neutrophils. (GENE)

When we think of aging by the various routes as stated above then we must posit that if CXCL9 is involved to a large degree than our behaviors must be triggering the immune cascade that needs lymphocyte type white blood cells to handle the damage from lifestyle induced inflammation. therefore, what does the science say about this?

High fat diets are known to trigger the CXCR family including CXCL9 which then targets the activation of T cells and macrophages in adipose tissue/fat cells which then promote the activation of low level inflammation throughout the local and systemic cellular pathways. This is one of a few mechanisms involved in driving obesity laden fat cells to be inflamed and immunologically counterproductive.. (Kiran et. al. 2021) High fat diets are those that are composed primarily of animal products including grain fed animal meats, dairy, coconut oil and other processed oils and lard. In combination with large volumes of fiber based vegetables and fruits, these fats seem to be benign. The problem appears to be driven by the types and combinations of fats and refined sugars more than fat in and of itself.

Diabetes and insulin resistance have also been shown to have strong connections to CXCL chemokines including CXCL9 via activation through bacterial dysbiosis and systemic lipopolysaccharides from bacterial cell walls. Viruses are also a part of this process. Diet induces these changes at the microbiome and systemic level.

The research on other links to the CXCL9 issue will be evolving and we will be watching. I suspect that the main players are all involved, diet, sedentary behavior, chemicals and stress.

In my understanding of the research, the TAKE HOME POINT is:
The Standard American high fat and sugar diet turns on cassettes of innate immune mediated cell signaling molecules like CXCL9 which then recruit large volumes of T cells and macrophages leading to lots of local tissue inflammation that eventually lead to the major metabolic diseases that plague America. Therefore, having CXCL9 as a possible surrogate marker of aging makes sense as inflammation is the main driver of early death for humans.

Technical but necessary to yet again guide us in our decision making when the federal and state governments are not working to help reduce human disease burdens by curtailing the access to cheap subsidized SAD type foods.

To think that we may be able to predict and educate individuals on death risk from infectious diseases like COVID and also chronic diseases of aging like diabetes in advance. That will be amazing!

One question? Will they listen and change behavior with this prevention based knowledge?

I hope so,


Dr. M

Sayed Nature Aging
Kiran Frontiers in Immunology
Tokunaga Cancer Treat Rev
Schertzer Diabetes