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Olfactory Receptor 558 (Olfr558) and Blood Pressure Regulation in Aging

Award Number: R21AG081683
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Olfactory Receptor 558 (Olfr558) and Blood Pressure Regulation in Aging - Project Summary Olfactory Receptors (ORs) comprise the largest gene family in the genome, and ORs serve key functions in a variety of tissues beyond the nose. We have identified an evolutionarily conserved OR, Olfr558, which localizes to vascular smooth muscle cells and plays a role in blood pressure regulation. It is well-established, in both humans and in animal models, that normotensive premenopausal females have lower blood pressure than normotensive males by approximately ~10mmHg. In contrast, blood pressure is similar in postmenopausal females and males, due to an increase in female blood pressure with aging. We find that sex differences in blood pressure are absent in Olfr558 knockout (KO) mice, and, that wild-type (WT) but not KO females increase blood pressure with aging. In this proposal, we will explore the role of Olfr558 in mediating changes in blood pressure in aging. In Aim 1, we will compare blood pressure by telemetry between WT and KO mice which are young (4-7 months, male and female), aged (18-22 months, male and female), or young (4-7 months) females in whom menopause has been chemically induced via VCD (4-vinylcyclohexene diepoxide). In Aim 2, we will use tissues from these same mice to assay how renin (Aim 2a) and vascular reactivity (Aim 2b) are altered in WT vs KO in these various groups. These studies will uncover the role of a well-conserved OR in the cardiovascular physiology of aging, and in so doing will reveal novel insights into sex differences, blood pressure regulation, aging, and menopause.


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: 2024 ( Subtotal = $204,688 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	2	2/2/2024	NON-COMPETING CONTINUATION	$184,219
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	001	2	6/28/2024	NON-COMPETING CONTINUATION	$20,469
														Subtotal = $204,688

Issue Date FY: 2023 ( Subtotal = $245,625 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	1	5/11/2023	NEW	$245,625
														Subtotal = $245,625

Grand Total All Awards = $450,313

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Olfactory Receptor 558 (Olfr558) and Blood Pressure Regulation in Aging

Award Number: R21AG081683

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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