Wednesday, July 2, 2025 7/2/2025

Understanding Interorgan Communication Through Heterochronic Organ Transplantation

Award Number: U01AG086168
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

Group Awards By:

View Award Description

Understanding Interorgan Communication Through Heterochronic Organ Transplantation - SUMMARY Dynamics of interorgan communication and biological age change as a function of chronological age but these dynamics and the underlying mechanisms are not well understood. Organ transplantation offers a clinically most relevant model with donor/recipient age-discrepant combinations representing a clinical routine to meet the ever- increasing organ demands. Our published studies and preliminary data show that an elevated donor age drives the immunogenicity of organs leading to augmented alloimmune responses with higher acute rejection rates. This, in turn, is blunted with the increase of recipient age, demonstrating both clinical relevance and inter- organ/recipient communication. These clinically relevant scenarios raise the possibility of potential rejuvenation and/or accelerated aging when performing heterochronic organ transplants. We have shown that the recipient environment can affect the biological age of transplanted organs. Specifically, when transplanting old organs in young recipients, we observed the reduction of donor organ biological age. At the same time, old organs transplanted into young recipient mice promoted aging, which not only led to an accumulation of senescent cells in peripheral organs, but also to a decline of physical and cognitive functions. Our project brings together a synergistically positioned group of aging and transplantation researchers and clinicians. Vadim Gladyshev (MPI) is an expert on aging biomarkers and the biology of aging. Stefan Tullius (MPI) is a clinician/scientist who provides the clinical perspective. The latest generation of aging biomarkers based on omics approaches, combined with state-of-the-art model systems place us in an unprecedented position to study inter-organ dynamics of aging. Our hypothesis is that that young and old cells transferred with an organ transplant may exert rejuvenating and aging effects extrinsically. This hypothesis will be tested in our established transplant models of clinical relevance and confirmed using a unique clinical database. We also hypothesize that transplanted organs will acquire the biological age approaching that of recipients. This includes the situation wherein old donor organs will be rejuvenated in young recipients, potentially increasing the use of discarded organs. This approach is significant and innovative in (i) delineating novel mechanisms of interorgan communication in a clinically relevant heterochronic transplantation model with perturbation of specific tissues, (ii) the use of state-of-the-art tools of aging science to characterize changes in biological age dynamics, (iii) the use of detailed mechanistic approaches to pinpoint changes in interorgan communication upon biological age perturbation; (iv) synergistic efforts of research groups combining deep complementary expertise in preclinical and clinical studies of aging biology and transplant medicine; and (v) real-world implications of the proposed work. These studies position us to substantially advance understanding of interorgan communication with regard to biological age, with the potential to delineate novel pathways in support of organ rejuvenation and the prevention of transferring age- accelerating effects with organ transplantation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $671,950 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Aging Research	001	2	6/9/2025	NON-COMPETING CONTINUATION	$54,852
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Aging Research	000	2	3/6/2025	NON-COMPETING CONTINUATION	$617,098
														Subtotal = $671,950

Issue Date FY: 2024 ( Subtotal = $685,664 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Aging Research	000	1	5/29/2024	NEW	$685,664
														Subtotal = $685,664

Grand Total All Awards = $1,357,614

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Understanding Interorgan Communication Through Heterochronic Organ Transplantation

Award Number: U01AG086168

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer