# Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan

> **NIH NIH K99** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $113,161

## Abstract

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.

## Key facts

- **NIH application ID:** 10468187
- **Project number:** 5K99AG068239-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Shangang Zhao
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $113,161
- **Award type:** 5
- **Project period:** 2021-08-15 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468187

## Citation

> US National Institutes of Health, RePORTER application 10468187, Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan (5K99AG068239-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10468187. Licensed CC0.

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