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Motherhood, pair bonding and parental relatedness as modulators of epigenetic aging

Award Number: P20GM109091
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/10/2014
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Motherhood, pair bonding and parental relatedness as modulators of epigenetic aging - Summary Sex and gender differences in aging and other health outcomes are frequently severely confounded by behavioral and environmental factors, mandating the use of animal models. Epigenetic age estimators provide a powerful tool in determining the epigenetic age alleviating the necessity of monitoring cohorts of animals throughout their lives in captivity or in the wild. The present study, by using outbred deer mice (Peromyscus) will explore how genetic relatedness of parents, history of social interactions, and CDK8/19 inhibition impact epigenetic age. The study relies on preliminary data indicating differences in the rate of epigenetic aging between males and females upon these interventions. Mechanistically, to link genetic relatedness with aging we will focus on the induction of endoplasmic reticulum (ER) stress, that reportedly differs between men and women. For our studies both monogamous and polygamous Peromyscus will be used. Specifically, we will (a). test if ER stress in females is more dependent on overall heterozygosity status than in males. Peromyscus male and female offspring of parents that differ in their genetic relatedness, as well as fibroblasts cultured in vitro, will be evaluated for ER stress and the resulting UPR, by analyzing the levels of a roster of chaperones that reflect ER stress. For our analysis we will utilize animals from all different stocks of Peromyscus as well as F1 hybrids between different stocks and species. (b). we will explore how the biobehavioral environment impacts epigenetic age estimators. We propose to test how pair bonding, disruption and biparental care, impact comparatively epigenetic aging in males and females, both the offspring as well as their parents. (c). we will explore the impact of CDK8/19 inhibition in epigenetic aging. Pharmacological interventions aiming to alleviate aging, besides providing avenues for the development of anti-aging therapies they also point to disparities impacting differentially the different sexes. Preliminary findings in mice indicate that inhibition of cyclin dependent kinases (CDK) 8/19, which regulate signal-induced transcription represents an avenue that may hold significant anti-aging value, preferentially towards females. Here we propose to explore if CDK8/19 inhibition decreases the epigenetic age, and alleviates telomere attrition and mitochondrial abundance of outbred deer mice. The proposed study constitutes a first effort to describe sex-based disparities in epigenetic aging in relation socioenvironmental factors and choices that impact the women’s social environment in the context of pair bonding and parents’ genetic relatedness. A. pharmacological intervention that prevents agent preferably in women will also be evaluated.


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 = $0 )
2025	2024	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	004	10	8/28/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	10	8/28/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	003	10	8/28/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	10	8/28/2025	NON-COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	10	8/28/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $289,084 )
2024	2024	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	10	8/21/2024	SUPPLEMENT FOR EXPANSION	$289,084
2024	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	10	9/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $289,084

Issue Date FY: 2023 ( Subtotal = $3,802,882 )
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	003	10	9/5/2023	SUPPLEMENT FOR EXPANSION	$205,696
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	004	10	9/11/2023	SUPPLEMENT FOR EXPANSION	$273
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	10	7/14/2023	SUPPLEMENT FOR EXPANSION	$298,000
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	005	10	9/19/2023	SUPPLEMENT FOR EXPANSION	$1,063,913
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	10	6/21/2023	NON-COMPETING CONTINUATION	$2,235,000
2023	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	9	11/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,802,882

Issue Date FY: 2022 ( Subtotal = $2,482,396 )
2022	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	9	5/19/2022	NON-COMPETING CONTINUATION	$2,235,000
2022	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	9	8/5/2022	SUPPLEMENT FOR EXPANSION	$247,396
														Subtotal = $2,482,396

Issue Date FY: 2021 ( Subtotal = $2,856,535 )
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	8	9/10/2021	SUPPLEMENT FOR EXPANSION	$249,035
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	8	5/21/2021	SUPPLEMENT FOR EXPANSION	$372,500
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	8	5/10/2021	NON-COMPETING CONTINUATION	$2,235,000
														Subtotal = $2,856,535

Issue Date FY: 2020 ( Subtotal = $2,235,000 )
2020	2020	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	004	7	9/22/2020	NON-COMPETING CONTINUATION	$0
2020	2020	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	003	7	7/22/2020	NON-COMPETING CONTINUATION	$2,235,000
2020	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	6	4/3/2020	COMPETING CONTINUATION	$0
2020	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	6	4/11/2020	COMPETING CONTINUATION	$176,185
2020	2018	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	5	4/11/2020	NON-COMPETING CONTINUATION	-$176,185
														Subtotal = $2,235,000

Issue Date FY: 2019 ( Subtotal = $2,235,000 )
2019	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	6	7/16/2019	COMPETING CONTINUATION	$2,235,000
2019	2018	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	5	7/11/2019	NON-COMPETING CONTINUATION	$0
2019	2018	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	5	5/15/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,235,000

Issue Date FY: 2018 ( Subtotal = $2,200,465 )
2018	2018	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	000	5	5/2/2018	NON-COMPETING CONTINUATION	$2,200,465
														Subtotal = $2,200,465

Issue Date FY: 2017 ( Subtotal = $2,200,465 )
2017	2017	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	001	4	7/10/2017	NON-COMPETING CONTINUATION	$220,045
2017	2017	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	000	4	4/25/2017	NON-COMPETING CONTINUATION	$1,980,420
														Subtotal = $2,200,465

Issue Date FY: 2016 ( Subtotal = $2,200,465 )
2016	2016	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	3	5/16/2016	NON-COMPETING CONTINUATION	$2,200,465
														Subtotal = $2,200,465

Issue Date FY: 2015 ( Subtotal = $2,200,465 )
2015	2015	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	2	4/30/2015	NON-COMPETING CONTINUATION	$2,200,465
														Subtotal = $2,200,465

Issue Date FY: 2014 ( Subtotal = $2,535,340 )
2014	2014	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	1	7/3/2014	NEW	$2,535,340
														Subtotal = $2,535,340

Grand Total All Awards = $25,238,097

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Motherhood, pair bonding and parental relatedness as modulators of epigenetic aging

Award Number: P20GM109091

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/10/2014

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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