The lymphatic system is vital to the correct operation of the immune response: lymph nodes are where immune cells communicate with one another in order to direct the response to invading pathogens and other threats. Unfortunately lymph nodes deteriorate with age, becoming inflammatory and fibrotic, no longer able to host the necessary passage and communication of immune cells. Researchers have demonstrated that, at least in late life, this can prevent improvements elsewhere in the aged immune system from producing the expected benefits in the immune response. What use extra immune cells or better immune cells if those cells cannot coordinate correctly? There are signs that lymph node degeneration may be due in part to the presence of senescent cells, in which case we might hope that senolytic therapies will help, but this has yet to be assessed by the research community.

What if new lymph nodes can be provided, however? Today's open access paper is a report on the generation and transplantation of organoids capable of functioning as lymph nodes. In mice, transplanted organoids can integrate with the lymphatic system and begin to perform the duties of lymph nodes. While these were not aged mice, and the transplanted organoids replaced lymph nodes that had been surgically removed, rather than augmenting those damaged by aging, this is still promising. This line of research could become one of the suite of approaches that will needed to restore the immune system of an older individual to full, youthful function.

The other necessary therapies for immune rejuvenation are: regrowth of the thymus, responsible for maturation of T cells of the adaptive immune system, and which atrophies with age; rejuvenation of the hematopoietic stem cell population in the bone marrow, source of all immune cells, and damaged and diminished in older individuals; and clearance of the senescent, exhausted, misconfigured, and otherwise broken or inappropriate immune cells that come to clutter up the immune system in late life. A few different approaches for each of these line items are at various stages of development. Given a the timescale of a decade or two we should be optimistic that the effects of aging on the immune system can be significantly reversed.

Therapeutic Regeneration of Lymphatic and Immune Cell Functions upon Lympho-organoid Transplantation