Summary
This project aims to investigate how genetic information loss, a key aspect of aging, is determined by the interplay among the hallmarks of aging, using both system-wide analysis and mechanistic interventions.
Genetic information flow in the Hallmarks of Aging: from system-level analytics to mechanistic interventions
US · IL
NIH
grant
awarded
#nih-5R01AG082739-03
What they want
The project proposes two main aims: (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. This will be accomplished using single cell RNA-seq data from skeletal muscle cells in young, middle-aged, and old male and female mice, computational analysis built on statistical physics and information theory, targeted genetic inhibition/overexpression using local shRNA approaches, and in vivo assessment of muscle functional integrity.
Deliverables
- A quantitative and mechanistic understanding of how hallmark-associated genes and processes (de)stabilize regulatory network interactions over an organism’s lifespan.
- A framework extendable to predict an individual’s biological age and to develop strategies to reprogram gene networks with the goal of preserving a more youthful phenotype.
Technical requirements
- Single cell RNA-seq data analysis from skeletal muscle cells in mice
- Computational analysis using statistical physics and information theory tools
- Targeted genetic inhibition/overexpression using local shRNA approaches
- In vivo assessment of muscle functional integrity
Key personnel
- Stem cell biologist (PI)
- Theoretical physicist (co-PI)
- Computational biologist (co-I)
- Molecular biologist (co-I)
