Mixing old and young: enhancing rejuvenation and accelerating aging
Ashley Lau, … , James L. Kirkland, Stefan G. Tullius
Ashley Lau, … , James L. Kirkland, Stefan G. Tullius
Published January 2, 2019
Citation Information: J Clin Invest. 2019;129(1):4-11. https://doi.org/10.1172/JCI123946.
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Mixing old and young: enhancing rejuvenation and accelerating aging

Abstract

Donor age and recipient age are factors that influence transplantation outcomes. Aside from age-associated differences in intrinsic graft function and alloimmune responses, the ability of young and old cells to exert either rejuvenating or aging effects extrinsically may also apply to the transplantation of hematopoietic stem cells or solid organ transplants. While the potential for rejuvenation mediated by the transfer of youthful cells is currently being explored for therapeutic applications, aspects that relate to accelerating aging are no less clinically significant. Those effects may be particularly relevant in transplantation with an age discrepancy between donor and recipient. Here, we review recent advances in understanding the mechanisms by which young and old cells modify their environments to promote rejuvenation- or aging-associated phenotypes. We discuss their relevance to clinical transplantation and highlight potential opportunities for therapeutic intervention.

Authors

Ashley Lau, Brian K. Kennedy, James L. Kirkland, Stefan G. Tullius

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Figure 2

Potential opportunities for therapeutic intervention.

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Potential opportunities for therapeutic intervention. Left: Older transp...
Left: Older transplant donors may be treated with senolytic agents before organ donation to a younger recipient. Senolytics with a minimal side effect profile are desirable for such applications. Middle: Treatment of the allograft with senolytic agents following organ procurement and prior to transplantation provides additional opportunities to intervene for the administration of senolytics, potentially via the addition of such compounds to organ preservation solutions and perfusates. Recent development of novel organ preservation methods permitting an extended duration of ex vivo organ maintenance may support not only senolytic treatment, but also additional means of therapeutic intervention. Right: Transplant recipients can also be treated with senolytics or senomorphics at the time of or subsequently to transplantation. Initial studies of these compounds indicate that the extent of their direct effects is specific to senescent cells.