Thursday, July 3, 2025 7/3/2025

Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan

Award Number: R00AG068239
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan - Project Summary/Abstract This proposal outlines an integrated training and research plan for Dr. Shangang Zhao to complete further academic training under the mentorship of Dr. Philipp E. Scherer and transition to an independent investigator specializing in the field of metabolism and geroscience. The overall objective of the research proposal is to explore the impact of a novel secreting protein, referred to as “J18” in healthspan and lifespan. Highly expressed in salivary glands both in mouse and human, large amounts of glycosylated J18 are secreted into saliva, an easily accessible biomaterial for multiple biomedical assays. J18 displays a unique pattern of regulation: Its level is increased in metabolically healthy states, such as fasting and calorie restriction, while decreased in metabolically adverse conditions, such as aging and obesity. With evidence accumulated from our J18 transgenic and knockout mouse models, we found that J18 is a novel lipid hydrolase, targeting on a unique lipid class to mediate its potent effects in promoting metabolic health. In addition, preliminary data suggest that increasing J18 level in our liver J18 transgenic mouse seems to prolong life span and deficiency of J18 in our J18 global KO mice reduces median life span. The basic principle of J18 physiology has been conserved remarkably well from mouse to human. These findings helped us define the physiological role of a previously unknown protein J18 in metabolic aspect. We will take advantage of our newly generated tissue specific transgenic and KO mouse models to manipulate systemic J18 level, along with the J18 targeted- unique lipid class, and will address: 1) saliva-derived J18 may be a potential and novel aging biomarker to allow easy prediction of an individual's life expectancy; 2) the impact of J18 in healthspan and lifespan. Combined, these studies will provide significant new insights into the physiological effects of J18 in healthspan and lifespan. The proposed role of J18 as a potential aging biomarker meets the urgent need for an easily assayable, validated and effective aging biomarker, and will greatly advance research in geroscience. Under the auspices of the University of Texas Southwestern Medical Center, along with the previous experience gained in studying the impact of adiponectin in healthspan, I will be mentored by internationally recognized leaders in the metabolism, and advised by the top aging experts, which will greatly facilitate the transition of my research career toward an independent investigator position.


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 = $244,020 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	000	5	3/7/2025	NON-COMPETING CONTINUATION	$224,100
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	001	5	6/9/2025	NON-COMPETING CONTINUATION	$19,920
														Subtotal = $244,020

Issue Date FY: 2024 ( Subtotal = $340,939 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	003	4	6/25/2024	NON-COMPETING CONTINUATION	$24,900
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	002	4	3/6/2024	NON-COMPETING CONTINUATION	$224,100
2024	2023	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	000	3	12/8/2023	EXTENSION WITH OR WITHOUT FUNDS	$91,939
2024	2023	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	001	3	2/23/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $340,939

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	000	3	3/31/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $833,959

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Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan

Award Number: R00AG068239

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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