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A Review of Immunosenescence


Immunosenescence is the age-related decline of the immune system. The reason why our immune systems start to fail and weaken as we age is not fully understood, and, indeed, there are a variety of hypotheses as to why this happens.


Inflammation certainly plays a role in this process, and it is well documented that inflammation has a considerable effect on immune cells such as macrophages, causing them to become dysfunctional and stop cleaning house. This is in line with the proposed concept of “inflammaging”, which describes an ever-increasing chronic background of inflammation from sources such as senescent cells, cell debris, and changes in the gut microbiota. This inflammaging then drives immune system dysfunction, which then creates more inflammation, continuing a downward spiral.

We recently learned that inflammation can cause problems with weight control by causing nerve-associated macrophages to stop signaling fat cells to release their stored energy[1]. We also know that macrophage dysfunction occurs in other tissues due to inflammation, and so it seems clear that inflammation plays at least a partial role in immune system decline.

Cellular Senescence

Some research suggests that the immune system declines due to its cells becoming senescent, just as other cell populations do. Over time, our cells reach their maximum number of divisions, or they are damaged and enter senescence and destroy themselves via apoptosis, a kind of programmed self-destruct sequence.

However, sometimes these cells resist apoptosis and cling on to life, but in doing so, they prevent fresh cells replacing them while generating inflammatory signals that cause nearby cells to become dysfunctional too. It is proposed that the immune system experiences the same senescence as our other cells, leading to immune system failure.

Stem cell depletion

Another player in immune system decline is stem cell depletion; for example, the thymus begins to shrink from an early age and eventually stops producing new T cells to help defend us from invading pathogens. The production of T cells is facilitated by thymic stem cells, which are gradually depleted over our lifetime, and eventually, we have so few T cells that we cannot fight off diseases such as flu and pneumonia, which often kill the elderly. Some attempts are currently being made to rejuvenate the thymus and have enjoyed some success.

A review of immunosenescence

It is likely the case that immunosenescence is a combination of all of these proposed things and more, and each plays a role in the resulting decline of our immune systems as we age. When it comes to establishing the exact chain of events that leads to immunosenescence, it will take reversing each of those causes to see what happens.

Today, we wanted to bring your attention to an open access paper that reviews the current knowledge of immunosenescence and provides a good introduction to the topic[2].


Developing the therapies that target the aging processes directly is likely the most expedient path to understanding immunosenescence, as these therapies will give us the tools with which to discover what drives the process. Approaches such as thymic rejuvenation or creating a replacement thymus, replacing lost stem cell populations such as hematopoietic stem cells that create all immune cells, removing overspecialized immune cells, and removing senescent cells are all valid approaches towards discovering how immunosenescence works.

Our knowledge is growing rapidly by the passing month, and more and more is being understood about the aging processes and how we might directly target them to prevent or reverse age-related diseases. It is almost certain that medicine is going to change dramatically in the next decade or two as our understanding grows.


[1] Camell, C. D., Sander, J., Spadaro, O., Lee, A., Nguyen, K. Y., Wing, A., … & Rodeheffer, M. S. (2017). Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature, 550(7674), 119-123.

[2] Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and Molecular Allergy, 15(1), 21.


About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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