Wednesday, March 18, 2026 3/18/2026

Targeting ER-mitochondrial calcium signaling to promote healthier aging

Award Number: R01AG073354
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Targeting ER-mitochondrial calcium signaling to promote healthier aging - Project Summary/Abstract Fundamental gaps remain in our understanding of the cell biological mechanisms that drive mitochondrial decline and associated age-related diseases. Organelles like the mitochondria and endoplasmic reticulum (ER) are physically and functionally linked, in part via sites of membrane contact. These lines of communication between mitochondria and other organelles represent an understudied avenue by which to therapeutically target mitochondrial function. Our long-term goal is to understand the physiological roles of inter-organelle communication during aging and age-related disease. In pursuit of that goal, our objective in this application is to determine how the ER regulates mitochondrial health during aging through its role as a platform for calcium signaling. We have exploited the simple anatomy of C. elegans and experimental advantages in genetics and microscopy to lay a foundation in this model for the study of ER-mitochondrial interactions. Similar to mammals, the worm ER calcium efflux channel, inositol triphosphate receptor (InsP3R), exerts potent control over mitochondrial bioenergetics, and we have extended the roles of InsP3R to regulation of mitochondrial gene expression and dynamics in the worm as well. Furthermore, the InsP3R regulates lifespan in C. elegans through mechanisms that depend upon mitochondrial function. Here we will test the hypothesis that ER remodeling in aging animals acts to trigger mitochondrial dysfunction and organismal decline by promoting aberrant subcellular calcium signaling and dynamics. To test this hypothesis, we will first determine whether the InsP3R is a cell autonomous regulator of mitochondrial function and lifespan. Secondly, we will identify the molecular mechanisms linking InsP3R activity to the diverse changes observed in mitochondrial behavior. Finally, we will determine how organellar remodeling of the calcium flux machineries initiates age-onset mitochondrial dysfunction. By revealing the mechanisms by which ER signaling governs mitochondrial health at the organismal level, these results will open new therapeutic avenues in treating mitochondrial pathologies.


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: 2026 ( Subtotal = $324,925 )
2026	2026	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	000	5	3/4/2026	NON-COMPETING CONTINUATION	$324,925
														Subtotal = $324,925

Issue Date FY: 2025 ( Subtotal = $318,427 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	000	4	3/26/2025	NON-COMPETING CONTINUATION	$292,433
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	001	4	6/13/2025	NON-COMPETING CONTINUATION	$25,994
														Subtotal = $318,427

Issue Date FY: 2024 ( Subtotal = $324,925 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	000	3	5/28/2024	NON-COMPETING CONTINUATION	$324,925
														Subtotal = $324,925

Issue Date FY: 2023 ( Subtotal = $324,925 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	000	2	4/12/2023	NON-COMPETING CONTINUATION	$324,925
														Subtotal = $324,925

Issue Date FY: 2022 ( Subtotal = $324,925 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Aging Research	000	1	6/13/2022	NEW	$324,925
														Subtotal = $324,925

Grand Total All Awards = $1,618,127

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Targeting ER-mitochondrial calcium signaling to promote healthier aging

Award Number: R01AG073354

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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