Thursday, November 21, 2024 11/21/2024

Mitochondrial DNA Copy Number and Sequence Variation in Relation to Age, Alzheimer's Disease Related Phenotypes and Age-related Metabolic Traits

Award Number: R01AG059727
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Abstract Aging is the main risk factor for many chronic diseases, including late onset Alzheimer's disease (LOAD) and many age-related metabolic diseases, such as obesity and diabetes. Using AD as an example, the number of people with AD doubles every 5 years beyond age 65. In 2017, 5.3 million Americans 65 years or older are affected by LOAD. The burden of health care costs for LOAD is enormous – $259 billion in 2017. Thus, early detection and treatment of these age-related diseases should be a core tenet of public health. Research is needed to guide such efforts. Over the last decade, accumulating evidence has linked aging to mitochondrial dysfunction. Mitochondria are tiny powerhouses, generating more than 90% of energy to support normal cellular function. Mitochondria contain their own genome (mtDNA) which is both polymorphic and heteroplasmic, i.e., two or more mtDNA alleles can co-exist in the same cell due to the presence of many mtDNA molecules within any cell. Previous studies in Europeans have found that reduced mtDNA copy number was associated with frailty and higher mortality among elderly. Furthermore, reduced mtDNA copy number in human cerebrospinal fluid was observed at least a decade before clinic AD symptoms develop. These findings in Europeans need to be generalized in other ethnic groups. Several hundreds of mtDNA rare mutations have been described to cause mostly rare, yet severe maternally inherited diseases. A limited number of common mtDNA polymorphisms were examined in relation to metabolic disorders, dementia and cognitive functions. Robust associations, however, haven't been established between common mtDNA polymorphisms and age-related common diseases. In most of these previous studies, heteroplasmic mtDNA mutations haven't been well studied with respect to aging and age-related human diseases because, until recently, sequencing has been extremely costly. Studying a spectrum of mtDNA mutations along with mtDNA copy number in relation to age-related traits in large samples has now become possible thanks to drastically decreased whole genome sequencing costs. This proposed study will leverage five prospective cohorts, each with whole genome sequencing data generated from the National Heart, Lung and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) and extensive cognitive, brain structure, and cardiometabolic measures. The expected outcomes of the work proposed are to 1) develop a novel statistical method to identify age-related heteroplasmic (i.e., somatic) mtDNA mutations, and 2) develop a statistical framework to analyze mtDNA copy number and heteroplasmic mutations in relation to key age-related disorders, include LOAD and age-related metabolic traits. Results of this investigation are expected to advance understanding of the role of aging on the mitochondrial genome, and in turn, the contributions of mitochondrial genome to age-related traits. Equally important, a positive impact of this project will be advancing knowledge of the role of mtDNA in a spectrum of age-related complex phenotypes.


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 = -$5,527 )
2025	2021	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	4	10/11/2024	NON-COMPETING CONTINUATION	-$5,527
														Subtotal = -$5,527

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	4	4/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $635,620 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	4	6/16/2021	NON-COMPETING CONTINUATION	$635,620
														Subtotal = $635,620

Issue Date FY: 2020 ( Subtotal = $635,620 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	3	7/8/2020	NON-COMPETING CONTINUATION	$635,620
														Subtotal = $635,620

Issue Date FY: 2019 ( Subtotal = $635,620 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	2	7/19/2019	NON-COMPETING CONTINUATION	$635,620
2019	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	1	4/16/2019	NEW	$0
														Subtotal = $635,620

Issue Date FY: 2018 ( Subtotal = $693,145 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	1	9/10/2018	NEW	$693,145
														Subtotal = $693,145

Grand Total All Awards = $2,594,478

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mitochondrial DNA Copy Number and Sequence Variation in Relation to Age, Alzheimer's Disease Related Phenotypes and Age-related Metabolic Traits

Award Number: R01AG059727

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer