Abstract

Protein translation (PT) declines with age in invertebrates, rodents, and humans. It has been assumed that elevated PT at young ages is beneficial to health and PT ends up dropping as a passive byproduct of aging. In Drosophila, we show that a transient elevation in PT during early-adulthood exerts long-lasting negative impacts on aging trajectories and proteostasis in later-life. Blocking the early-life PT elevation robustly improves life-/health-span and prevents age-related protein aggregation, whereas transiently inducing an early-life PT surge in long-lived fly strains abolishes their longevity/proteostasis benefits. The early-life PT elevation triggers proteostatic dysfunction, silences stress responses, and drives age-related functional decline via juvenile hormone-lipid transfer protein axis and germline signaling. Our findings suggest that PT is adaptively suppressed after early-adulthood, alleviating later-life proteostatic burden, slowing down age-related functional decline, and improving lifespan. Our work provides a theoretical framework for understanding how lifetime PT dynamics shape future aging trajectories.

The transient elevation in protein translation during early-adulthood in Drosophila imposes long-lasting negative impacts on future aging trajectories by triggering proteostatic dysfunction at old ages.

Details

Title
Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
Author
Kim, Harper S. 1 ; Parker, Danitra J. 2 ; Hardiman, Madison M. 3 ; Munkácsy, Erin 4 ; Jiang, Nisi 4   VIAFID ORCID Logo  ; Rogers, Aric N. 5 ; Bai, Yidong 6 ; Brent, Colin 7 ; Mobley, James A. 8 ; Austad, Steven N. 9   VIAFID ORCID Logo  ; Pickering, Andrew M. 10   VIAFID ORCID Logo 

1  University of Alabama at Birmingham, Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187); University of Alabama at Birmingham, Medical Scientist Training Program, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187); University of Texas Health San Antonio, Barshop Institute for Longevity and Aging Studies, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633); University of Texas Health San Antonio, Medical Scientist Training Program, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633) 
2  University of Alabama at Birmingham, Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187); McGovern Medical School at UTHealth, Department of Integrative Biology and Pharmacology, Houston, USA (GRID:grid.265892.2) 
3  University of Alabama at Birmingham, Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187) 
4  University of Texas Health San Antonio, Barshop Institute for Longevity and Aging Studies, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633) 
5  MDI Biological Laboratory, Bar Harbor, USA (GRID:grid.250230.6) (ISNI:0000 0001 2194 4033) 
6  University of Texas Health San Antonio, Barshop Institute for Longevity and Aging Studies, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633); University of Texas Health San Antonio, Department of Cell Systems and Anatomy, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633) 
7  USDA-ARS Arid Land Agricultural Research Center, Maricopa, USA (GRID:grid.512828.4) (ISNI:0000 0004 9505 5038) 
8  University of Alabama at Birmingham, Department of Anesthesiology and Perioperative Medicine, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187) 
9  University of Alabama at Birmingham, Department of Biology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187); University of Alabama at Birmingham, Nathan Shock Center, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187) 
10  University of Alabama at Birmingham, Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000 0001 0634 4187); University of Texas Health San Antonio, Barshop Institute for Longevity and Aging Studies, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633); McGovern Medical School at UTHealth, Department of Integrative Biology and Pharmacology, Houston, USA (GRID:grid.215352.2); University of Texas Health San Antonio, Department of Molecular Medicine, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000 0001 2184 5633) 
Pages
5021
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-40618-x
ProQuest document ID
2852874463
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.