Hem » Articles » Health » The hallmarks of aging – Part 4

This is the final part in our hallmarks of aging series, and focuses on the final two hallmarks that contribute to the body’s decline.

Stem Cell Exhaustion

As we age, our tissues lose the power to regenerate.

Stem cells are created when we’re still embryos, allowing a small number of cells to divide and create all of the tissues in our bodies. These cells are known as embryonic stem cells and have the ability to differentiate into anything. However, by the time we’re born, we don’t have any of these remaining. Instead we have adult stem cells which are only found in specific places- the bone marrow, the muscles, the intestines and the brain. These can only become things related to the area they inhabit; Intestinal stem cells can repair the intestine, muscle stem cells can repair muscles, bone marrow cells can become both red and white (immune) blood cells.

As we age, our supply of these adult stem cells decreases, as a result of the previous hallmarks of aging combined, and are damaged, no longer able to divide, or simply used up. This means we’re unable to continue to repair our bodies, or produce more immune cells for the blood, and thus our muscle strength, digestive ability and immune system decreases in effectiveness (1–4). However, there are trials being done to see if the exhaustion of stem cells can be reversed, which means that the rejuvenation of adult tissues is possible in the future (5)!

Altered Intercellular Communication

The cells of our body communicate with one another. This process is vital for the normal functioning of our body, as it helps control everything from our nutrient levels to our mood. However, as we age, our ability to accurately control the signals our cells send out fades. This leads to altered intercellular communication .

One of the main ways this causes damage to the body is through the rise in inflammatory signals (6). The aging cells now send out more signals to increase inflammation and also fail to send out signals to stop it. This inflammaging has many causes- misfolded proteins caused by one of the earlier hallmarks, “loss of proteostasis”, can act as danger signals that make the body react to an unknown presence with an inflammatory immune response, or another hallmark, “epigenetic changes”, can lead to a cell producing more of an inflammatory signal than intended.

All this results in a very high background level of inflammatory signals throughout the body. This leads to many other issues, interfering with the body trying to conduct normal repair mechanisms and causing autoimmune responses that contribute to aging.


This is the end of the series explaining what each of the hallmarks of aging are, but not the last time you’ll hear of them! The hallmarks have been the starting point for so much of the aging research that is now conducted, and so you can expect future articles on everything from how they’re used in therapies to how physical exercise can slow the effects of time.

Grace Marshall

Grace Marshall MSc

Nordic Executive Medicine


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  3. Pentinmikko N, Katajisto P. The role of stem cell niche in intestinal aging. Mech Ageing Dev. 2020 Oct;191:111330.
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  5. Rando TA, Chang HY. Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell. 2012 Jan 20;148(1-2):46–57.
  6. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4–9.