Research advances in the past decade have demonstrated that organismic aging occurs as the result of altered metabolism in cells and tissues, leading to heightened oxidative stress and immune imbalance. Because immune cells help regulate tissue and circulatory environments, they can significantly influence biological aging and immunometabolic tone throughout the body. For this reason, aging of immune cells and subsequent changes in the regulation of immunity itself may have disproportionately great influence over whole-body senescence.
The innate immune system must detect pathogens and pathogenic tissue changes, and it is charged with cataloguing an organism’s ever-expanding immune memory bank. In an immune response, innate and adaptive arms of immunity coordinate the mobilization of resources to address threats and restore tissue homeostasis. Both of these aspects of immunity undergo aging; while innate immunity tends to become more active as genetic damage, oxidative stress, and epigenetic repatterning progress over a lifetime, adaptive immunity tends to become less targeted and efficient with age. The result of these changes is often an individualized mosaic of reduced immunity to pathogens (immunosuppression) paired with heightened propensity for inflammation.
This study employed an animal model of accelerated hematopoietic cell aging, selectively deleting a DNA-repair gene from these cell populations in mice. These mutant mice were compared over time with normal ‘wild-type’ and with progeroid (prematurely senescent) mice for changes in immune cell populations, vital organ function, and lifespan. The team then examined the effects of transplanting spleen cells from young animals into aged ones, and vice versa. Finally, they treated the genetically-altered mice with the senolytic (senescent cell-clearing) agent rapamycin to observe its influence on SASP expression.
Immune Aging May Drive Overall Aging
Senescent immune cells are key contributors to systemic aging through their impaired function and proinflammatory signaling, with subsequent alterations in the regulation of immunity. Senolytics can aid the elimination of these aged and dysfunctional cells, yet senolytic agents tend to be quite selective in the types of cells they influence. This study identifies immune cells as a pivotal target for senolytic substances. The use of appropriate senolytics may potentially help preserve vital organ function and limit immunosuppression and inflammation during aging.