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Aging and the nuclear lamina in mitotic stem cells

Award Number: R21AG072397
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Aging and the nuclear lamina in mitotic stem cells - PROJECT SUMMARY Tissue homeostasis depends upon the regulated production of differentiated cells to replace those that are damaged or defective. Homeostasis declines with age, largely because of decreases in stem cell number and/or function. To intervene in the aging process, it is critical to understand mechanisms involved in stem cell homeostasis. We discovered that paradigmatic Drosophila female germline stem cells (fGSCs) use a non-canonical mode of mitosis, wherein the nuclear envelope and nuclear lamina remain throughout mitosis. In this mode, mitotic spindles are nucleated from centrosomes embedded in the retained nuclear lamina. This mode of mitosis has gone unrecognized, due to the rarity of stem cell divisions and the globally accepted assumption that metazoan mitoses involve nuclear lamina dispersal. As such, how the mitotic nuclear lamina impacts asymmetric stem cell divisions and stem cell maintenance is unknown. The long-term goal of these studies is to define contributions of the mitotic nuclear lamina to fGSC homeostasis during aging. We capitalize on this natural in vivo stem cell population that demonstrates rapid, age-dependent declines in stem cell functions to address two aims. Aim 1 will define how biological aging affects the mitotic nuclear lamina. Aim 2 will define the role of the nuclear lamina checkpoint kinases in physiological aging. Experiments in this proposal will establish contributions of the newly identified mitotic nuclear lamina to stem cell maintenance. These studies have the potential to provide insights into lamin associated diseases such as progeria and provide insights to advance therapeutics that delay or eliminate stem cell loss during natural 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: 2024 ( Subtotal = -$2,551 )
2024	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Aging Research	000	2	10/18/2023	NON-COMPETING CONTINUATION	-$2,551
														Subtotal = -$2,551

Issue Date FY: 2022 ( Subtotal = $193,125 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Aging Research	000	2	12/30/2021	NON-COMPETING CONTINUATION	$173,812
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Aging Research	001	2	4/25/2022	NON-COMPETING CONTINUATION	$19,313
														Subtotal = $193,125

Issue Date FY: 2021 ( Subtotal = $231,750 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Aging Research	000	1	3/31/2021	NEW	$231,750
														Subtotal = $231,750

Grand Total All Awards = $422,324

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Aging and the nuclear lamina in mitotic stem cells

Award Number: R21AG072397

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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