Vieillissement - Publications Scientifiques

Dernière publication 31/10/2023

Transplanting old organs promotes senescence in young recipients

In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the...

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    [title] => Transplanting old organs promotes senescence in young recipients
    [paragraph] => Transplanting old organs promotes senescence in young recipients
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Authors
Iske J, Roesel MJ, Martin F, Schroeter A, Matsunaga T, Maenosono R, Tripathi U, Xiao Y, Nian Y, Caldarone BJ, Vondran FWR, Sage PT, Azuma H, Abdi R, Elkhal A, Pirtskhalava T, Tchkonia T, Kirkland JL, Zhou H, Tullius SG.

 Lab
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Journal
Am J Transplant.
Abstract
In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce senescence in younger recipients, promoting age-related pathologies. When performing isogeneic cardiac transplants between age-mismatched C57BL/6 old donor (18 months) mice and young and middle-aged C57BL/6 (3- or 12- month-old) recipients , we observed augmented frequencies of senescent cells in draining lymph nodes, adipose tissue, livers, and hindlimb muscles 30 days after transplantation. These observations went along with compromised physical performance and impaired spatial learning and memory abilities. Systemic levels of the senescence-associated secretory phenotype factors, including mitochondrial DNA (mt-DNA), were elevated in recipients. Of mechanistic relevance, injections of mt-DNA phenocopied effects of age-mismatched organ transplantation on accelerating aging. Single treatment of old donor animals with senolytics prior to transplantation attenuated mt-DNA release and improved physical capacities in young recipients. Collectively, we show that transplanting older organs induces senescence in transplant recipients, resulting in compromised physical and cognitive capacities. Depleting senescent cells with senolytics, in turn, represents a promising approach to improve outcomes of older organs.
BIOSEB Instruments Used
Grip strength test (BIO-GS4)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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