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T Cell Homeostasis and Function in Immune Senescence

Award Number: R37AG020719
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2001
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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T Cell Homeostasis and Function in Immune Senescence - The premise of this project is that studying immune aging in laboratory mice that are experiencing a natural burden of major infectious, psychological and physical stressors will better mirror and inform immune aging in humans. Old age is accompanied by increased vulnerability to infectious diseases, due to the aging of the immune system. Immune aging is, in turn, substantially influenced by the presence of a lifelong, persistent infection with the cytomegalovirus (CMV). In the past period of this award, we studied mouse CMV (mCMV) in isolation (as a latent persistent mono-insult). We concluded that mCMV substantially degraded the healthspan of mice, but only in the presence of major stressors, such as ionizing radiation or another infection. We propose to advance studies of mCMV and immune aging in mice experiencing a natural burden of major infectious, psychological and physical stressors that are likely to be encountered by humans repeatedly during the lifespan. We hypothesize that life-long latent mCMV infection contributes to the demise of T-cell and global immune function, directly proportional to the stress-induced viral reactivation and loss of immune control over mCMV. To test this, animals will be exposed to (i) low dose ionizing radiation; or (ii) low dose stress hormone corticosterone; (iii) non- specific pathogen free (non-SPF) microbiota, which has been shown to induce the immune system in SPF mice to become similar to that of humans. We will test how this impacts mCMV reactivation and immune responses to vaccination and lethal infection. We will ask: SA1. Do repeated individual stressors, commonly experienced by humans, worsen the impact of mCMV on immune function with age? SA2. Is the impact of life stressors on immune aging and overall health in mCMV-positive mice caused by CMV DNA replication/reactivation? These experiments will, for the first time, introduce key physiological variables of importance to human immune aging into a well-controlled murine model of mCMV, aging and infection. We anticipate that this poly-insult model will substantially mirror immune aging in humans, and provide ground for new discoveries that will pave the way for combined antiviral and stress-control therapies to improve T cell and overall immunity and healthspan outcomes in aging.


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 = $457,456 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	18	3/6/2025	NON-COMPETING CONTINUATION	$420,112
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	001	18	6/9/2025	NON-COMPETING CONTINUATION	$37,344
														Subtotal = $457,456

Issue Date FY: 2024 ( Subtotal = $466,791 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	003	17	7/1/2024	NON-COMPETING CONTINUATION	$46,679
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	002	17	3/14/2024	NON-COMPETING CONTINUATION	$420,112
2024	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	001	16	3/12/2024	EXTENSION WITH OR WITHOUT FUNDS	$303
2024	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	15	3/12/2024	NON-COMPETING CONTINUATION	-$303
														Subtotal = $466,791

Issue Date FY: 2023 ( Subtotal = $466,791 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	16	5/11/2023	EXTENSION WITH OR WITHOUT FUNDS	$466,791
														Subtotal = $466,791

Issue Date FY: 2022 ( Subtotal = $405,010 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	15	5/18/2022	NON-COMPETING CONTINUATION	$405,010
														Subtotal = $405,010

Issue Date FY: 2021 ( Subtotal = $405,010 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	14	4/16/2021	NON-COMPETING CONTINUATION	$405,010
														Subtotal = $405,010

Issue Date FY: 2020 ( Subtotal = $734,398 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	13	4/14/2020	NON-COMPETING CONTINUATION	$405,010
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	001	13	7/22/2020	SUPPLEMENT FOR EXPANSION	$329,388
														Subtotal = $734,398

Issue Date FY: 2019 ( Subtotal = $405,010 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	12	3/21/2019	NON-COMPETING CONTINUATION	$405,010
														Subtotal = $405,010

Issue Date FY: 2018 ( Subtotal = $405,010 )
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	11	4/1/2018	COMPETING CONTINUATION	$377,394
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	001	11	8/31/2018	COMPETING CONTINUATION	$27,616
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	002	11	9/15/2018	COMPETING CONTINUATION	$0
														Subtotal = $405,010

Grand Total All Awards = $3,745,476

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T Cell Homeostasis and Function in Immune Senescence

Award Number: R37AG020719

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2001

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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