The Immune System Should be a High Priority Target in the Development of Rejuvenation Therapies

The immune system has many roles. It doesn't just destroy invading pathogens, but also hunts and kills potentially harmful cells, such as those that have become senescent or potentially cancerous. Further, immune cells are intricately involved in the processes of tissue maintenance. Regeneration from injury is a complicated dance of signals and changed states carried out between stem cells, immune cells, and somatic cells. In the central nervous system, immune cells take on additional responsibilities related to maintaining and changing synaptic connections between neurons.

The immune system fails with age. Its failure is complex, built of many separate, interacting failures that take place in both the biological systems responsible for manufacturing immune cells, and in the many distinct and varied populations that make up the immune system as a whole. The result is an immune system that is both chronically overactive, producing constant inflammation that disrupts normal tissue maintenance and function throughout the body, but also incapable of effectively destroying pathogens and cancerous or senescent cells.

It is precisely because the immune system is involved in so much of the correct function of the body and mind that it is an important target for the development of rejuvenation therapies. A considerable fraction of the dysfunction, frailty, suffering, and mortality of age is driven by the failure of the immune system, its decline into chronic inflammation. If the immune system of every 60-year old could be restored to that of a 40-year old, incidence of age-related disease and mortality could be expected to become significantly lower.

There are many potential approaches to restoring function to the aged immune system, a range of which are discussed by the authors of today's open access paper. For example: replacing the hematopoietic stem cell population responsible for creating immune cells; regenerating the involuted thymus, where T cells mature; selective destruction of problematic immune cell population that grow with age, such as senescent T cells or age-associated B cells; and so forth. The next few decades could well be a very inventive time in the treatment of immune system aging, given sufficient investment in the right lines of research and development.

Targeting immune dysfunction in aging

Aging is a multifactorial phenomenon that affects virtually all cells and organ systems in the human body resulting in a progressive functional impairment and loss of homeostasis. One of the most dysregulated systems in aging is the immune system, with alterations in several biological and physiological processes that have significant repercussions on the overall well-being of the organism. The main roles of the immune system include the defense of the host against pathogens, the maintenance of homeostasis with clearance of dead cells and the regulation of healing processes. These activities are performed by specialized cells, that can activate general immune responses (innate immunity) or build specialized long-lasting defense against specific antigens (adaptive immunity). The progressive deterioration of the immune system affects both of these systems in elderly individuals, increasing susceptibility to infections, cancer, and inflammatory diseases, while delaying wound healing processes and reducing the ability to build an antibody response to some types of vaccination.

Indeed, the incidence of several infectious diseases, both bacterial and viral, increases with age and can be modeled based on immune system decline. In the same computational study, the authors showed that this is also true for cancer, indicating that the alteration of the immune system in aging may contribute to increased cancer incidence in the elderly. This work expands the scientific evidence on the relation between aging, immunity and cancer, but the exact ways in which they affect and influence each other remains debatable. Also autoimmune diseases have been investigated in the context of aging, with some evidence suggesting that they tend to be less frequent and less severe in elderly individuals, consistent with an overall decline in immune cell activity.

The dysfunctional immune system in aging has been associated with two processes defined as "immunosenescence" and "inflammaging". Immunosenescence, first proposed more than 40 years ago, is defined by the gradual deterioration of the immune system, which loses its ability to respond to infections and build effective long-lasting immune memory. More recently, studies have highlighted how several cell types of the innate and adaptive immune system undergo phenotypic changes during aging that impair their basic functions. At the beginning of 2000, a second phenomenon that affects the immune system in aging was proposed, termed inflammaging. While inflammatory processes are essential for the defense against foreign pathogens and clearance of dead and aberrant cells, their dysregulation and overactivation in the elderly causes a chronic inflammatory state that persists and promotes the development of inflammatory diseases associated with aging. These two processes are deeply interconnected, and can influence and maintain each other to create an imbalanced immune environment that is not only dysfunctional, but even acts as a driver for diseases development.

Individual differences are now starting to delineate a personalized way of aging that adds complexity to the investigation of deregulated processes. In this view, the identification of different immune ageotypes will help define subpopulations of elderly individuals with characteristic immune signatures and their longitudinal monitoring might help develop potential personalized anti-aging treatments. In this review, we report and discuss the contributions of different immune cells in aging and address the latest therapeutic options that have been proposed with the overall goal to rejuvenate or at least revitalize the immune system and slow down or even reverse immune aging.


My view is that improving the immune system is likely the HIGHEST priority in enhancing human longevity, especially that of improving thymus function.

Posted by: Ky' Zan' at August 19th, 2021 9:47 PM

Is Repair Bio still doing anything with Thymus Regeneration?

Posted by: jimofoz at August 20th, 2021 12:46 AM

@jimofoz: Repair Biotechnologies is focused on the cholesterol degrading platform at this time. Regeneration of the thymus is a project of interest for me, and I will likely be returning to it in the future.

Posted by: Reason at August 20th, 2021 12:56 PM

I have read in the Book 📕 "AGELESS" by Andrew Steele, that castration at a young age will restore thymus and prolong average lifespan to 100 years or more. Sex hormones is one cause of involution of thymus. No one wants to be castrated voluntarily - longer life is not worth reduced quality of life. But if someone can find a method to reduce effect of sex hormones on thymus without castration - it may be worth experimenting on animals.

Posted by: Nicholas D. at August 20th, 2021 6:39 PM
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