Interorgan communication in aging in drosophila

Active Cooperative Agreement Awarded Last action

Award ID
U01AG086143
Recipient
Awarding agency
Obligated
$5,217,370

Award facts

Assistance listing
93.866 Aging Research
Completion date 52% complete
Place of performance
Boston, MA 02115, USA

Award details come from USAspending.gov.

Description

Abstract
Aging is a complex condition with diverse physiological effects ranging from the cellular to organismal levels, such as the dysregulation of metabolism. While many distinct aspects of aging have been characterized, a wholistic understanding of how these aspects function together will be necessary to define and treat age- associated health decline and diseases more effectively. One way to address this is by better understanding the inter-organ communication (IOC) that coordinates aging mechanisms between tissues. Our proposal focuses on the IOC between aging metabolic tissues and how this communication alters metabolism and impacts biological age. We propose a multi-omics approach of single-cell transcriptomics, tissue-specific proteomics, metabolomics, and bioinformatics to work towards a system-level understanding of IOC, metabolism, and aging in drosophila melanogaster. We have recently generated the aging fly cell atlas (afca), the most comprehensive single-cell transcriptomic dataset to-date of an entire aging organism. We will exploit and build upon these data to identify novel IOC, tissue-specific metabolic reprogramming, and SEX differences during natural fly aging. Additionally, we propose system-level IOC and metabolomic characterization of 1) pro-longevity models of mtor inhibition in adult flies using tissue-specific foxo activation and rapamycin feeding and 2) advanced aging models of degenerative muscle stress and human TAU-induced neurodegeneration. We will correlate findings from these models with those from the afca to discover anti-aging targets within the IOC network that will modulate aging metabolism in a tissue-specific fashion. This work has the potential to 1) better understand how organismal metabolism is regulated via IOC; 2) develop strategies to enhance anti-aging therapies such as rapamycin; 3) identify disease mechanisms of muscle and neural degeneration that affect otherwise healthy distant tissues; 4) ultimately elucidate fundamental system-level aging biology and accelerate the discoveries of new anti-aging therapies.

Transactions

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Subawards

Subrecipient Amount Awarded
Baylor College Of Medicine The Li lab will apply the Fly Cell Atlas experimental and bioinformatic pipelines to dissect mechanisms of inter-organ communication in aging in Drosophila with… $780,878

Quick answers

Who received award U01AG086143?

U01AG086143 was awarded to President And Fellows Of Harvard College by National Institute on Aging (National Institutes of Health) on May 15, 2024.

How much is award U01AG086143 worth?

$5,217,370 has been obligated on U01AG086143.

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