Cardiology

Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation.


Icon for Nature Publishing Group Icon for PubMed Central Related Articles

Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation.

Nat Commun. 2020 08 27;11(1):4289

Authors: Iske J, Seyda M, Heinbokel T, Maenosono R, Minami K, Nian Y, Quante M, Falk CS, Azuma H, Martin F, Passos JF, Niemann CU, Tchkonia T, Kirkland JL, Elkhal A, Tullius SG

Abstract
Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses to injury and increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates with aging and augments immunogenicity. Ischemia reperfusion injury induces a systemic increase of cf-mt-DNA that promotes dendritic cell-mediated, age-specific inflammatory responses. Comparable events are observed clinically, with the levels of cf-mt-DNA elevated in older deceased organ donors, and with the isolated cf-mt-DNA capable of activating human dendritic cells. In experimental models, treatment of old donor animals with senolytics clear senescent cells and diminish cf-mt-DNA release, thereby dampening age-specific immune responses and prolonging the survival of old cardiac allografts comparable to young donor organs. Collectively, we identify accumulating cf-mt-DNA as a key factor in inflamm-aging and present senolytics as a potential approach to improve transplant outcomes and availability.

PMID: 32855397 [PubMed – indexed for MEDLINE]

Source link

Related posts

Functional parameters impairment after MRI in a patient with a transcatheter pacing system.

Newsemia

The impact of the aortic cusps fusion pattern and valve disease severity on the aortic wall mechanics in patients with bicuspid aortic valve.

Newsemia

heart failure; +107 new citations

Newsemia

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy

COVID-19

COVID-19 (Coronavirus) is a new illness that is having a major effect on all businesses globally LIVE COVID-19 STATISTICS FOR World