Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Genetic information flow in the Hallmarks of Aging: from system-level analytics to mechanistic interventions

Award Number: R01AG082739
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

Genetic information flow in the Hallmarks of Aging: from system-level analytics to mechanistic interventions - ABSTRACT Although aging is understood as a system-wide deterioration of cell and tissue function, it is nevertheless associated with specific hallmarks, first introduced by López-Otín et al. in 2013. Because these hallmarks have traditionally been studied in isolation, the relationships between them remain largely unknown, including whether hallmarks emerge at different times or in a hierarchical manner, or whether certain hallmarks (or genes therein) are the critical drivers of aging. We previously quantified the system-wide deterioration of cell function using a statistical physics approach, showing that the information communicated in transcriptional regulatory networks decreases with age. Here, we propose to investigate how this information loss is determined by the interplay among hallmarks, using both system-wide analysis and mechanistic interventions. Specifically, we aim (1) to map the trajectory, hierarchy, and impact of genetic information flow for each of the hallmarks of aging over time and according to sex; and (2) to mechanistically validate the effect of age on the transfer of genetic information. We will accomplish these aims using a combination of single cell RNA-seq data from skeletal muscle cells in young, middle-aged, and old male and female mice; computational analysis built on tools from statistical physics and information theory; targeted genetic inhibition/overexpression using local shRNA approaches; and in vivo assessment of muscle functional integrity. This innovative approach will be carried out by an interdisciplinary team comprising a stem cell biologist (PI), a theoretical physicist (co-PI), a computational biologist (co-I), and a molecular biologist (co-I), the breadth of which enhances feasibility, impact, and likelihood for success. The outcome of the proposed work will be a quantitative and mechanistic understanding of how hallmark-associated genes and processes (de)stabilize regulatory network interactions over an organism’s lifespan. Ultimately, we anticipate that this framework can be extended to predict an individual’s biological age and to develop strategies to reprogram gene networks with the goal of preserving a more youthful phenotype.


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 = $424,986 )
2025	2025	THE SPAULDING REHABILITATION HOSPITAL CORPORATION	300 1ST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Aging Research	000	3	7/10/2025	NON-COMPETING CONTINUATION	$424,986
														Subtotal = $424,986

Issue Date FY: 2024 ( Subtotal = $425,561 )
2024	2024	THE SPAULDING REHABILITATION HOSPITAL CORPORATION	300 1ST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Aging Research	000	2	5/7/2024	NON-COMPETING CONTINUATION	$425,561
														Subtotal = $425,561

Issue Date FY: 2023 ( Subtotal = $449,964 )
2023	2023	SPAULDING REHABILITATION HOSPITAL CORPORATION, THE	300 FIRST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Aging Research	000	1	9/20/2023	NEW	$449,964
														Subtotal = $449,964

Grand Total All Awards = $1,300,511

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic information flow in the Hallmarks of Aging: from system-level analytics to mechanistic interventions

Award Number: R01AG082739

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer