PERILIPIN 5: LINKING LIPID DROPLETS TO NUTRIENT SENSING AND HEALTHY AGING - PROJECT SUMMARY NUTRIENT SENSIN…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG070104_075
- FAIN
- R00AG070104
- Recipient
- VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $711,180
- Period
- Feb 1, 2024 – Jan 31, 2027
- Fiscal year
- 2024
- Place of performance state
- VA
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
PERILIPIN 5: LINKING LIPID DROPLETS TO NUTRIENT SENSING AND HEALTHY AGING - PROJECT SUMMARY NUTRIENT SENSING PATHWAYS (MTOR, AMPK, SIRTUINS) ARE CORE COMPONENTS UNDERLYING THE AGING PROCESS, LINKING POST-TRANSLATION MODIFICATIONS CRITICAL TO CELLULAR FUNCTION TO ENVIRONMENTAL FACTORS. TO DATE, RESEARCH IN THIS AREA HAS LARGELY FOCUSED ON INTERVENTIONS SUCH AS CALORIC OR PROTEIN RESTRICTION THAT DRIVE LIFESPAN OR SLOW AGING-RELATED MORBIDITIES. AN EMERGING AREA OF RESEARCH DERIVED FROM THESE INTERVENTION STUDIES HIGHLIGHTS THE POTENTIAL OF FAT CATABOLISM, THE LIPOLYTIC DEGRADATION OF TRIACYLGLYCEROL STORED WITHIN LIPID DROPLETS (LDS), AS A MAJOR FACTOR DURING THE AGING PROCESS. DESPITE ACCUMULATING EVIDENCE FOR A BENEFICIAL ROLE OF LIPOLYSIS, THE MECHANISM THAT LINKS LIPOLYSIS TO HEALTHSPAN IS POORLY UNDERSTOOD. DR. CHARLES NAJT RECENTLY IDENTIFIED THE LD PROTEIN PERILIPIN 5 (PLIN5) TO BE THE CRITICAL LINK BETWEEN LIPOLYSIS AND THE NUTRIENT SENSOR SIRT1; LOSS OF PLIN5 ABLATED ADIPOSE-TRIGLYCERIDE LIPASE (ATGL)-MEDIATED ACTIVATION OF SIRT1. OUR PUBLISHED AND PRELIMINARY DATA SHOW THAT IN RESPONSE TO CAMP/PKA SIGNALING, WHICH IS DRIVEN BY FASTING OR CALORIC RESTRICTION (CR), PLIN5 BINDS AND TRANSPORTS MONOUNSATURATED FAS (MUFAS) PRODUCED FROM LIPOLYSIS TO THE NUCLEUS. ONCE IN THE NUCLEUS, MUFAS LIBERATED FROM PLIN5 ALLOSTERICALLY ACTIVATE SIRT1. THESE RESULTS PROVIDE AN UNDERLYING MECHANISM EXPLAINING THE GROWING BODY OF LITERATURE THAT HAS LINKED MUFAS TO IMPROVED HEALTHSPAN. YET, WHILE CR OR INTERMITTENT FASTING, INTERVENTIONS SHOWN TO INCREASE HEALTHSPAN, INCREASE PLIN5 EXPRESSION, LITTLE IS KNOWN ABOUT THE DIRECT ROLE OF PLIN5 IN HEALTHSPAN OR LONGEVITY. A FEW STUDIES INDICATE PLIN5 EXPRESSION PEAKS AROUND MIDDLE AGE, SLOWLY DECREASING OVER TIME OR DRASTICALLY DECREASES IN OXIDATIVE TISSUES DURING METABOLIC DISEASE, YET THE CAUSE OF THESE CHANGES OR THE IMPACT OF DECREASED PLIN5 EXPRESSION IS UNKNOWN. THIS IS A SIGNIFICANT GAP IN KNOWLEDGE AS PLIN5 HAS BEEN SHOWN T