Expression of tardigrade intrinsically disordered proteins in C. elegans reveals variable effects on aging and stress
- 1University of Southern California
Abstract
Tardigrades survive extreme environmental stress by expressing intrinsically disordered proteins that stabilize cellular structures during cryptobiosis. Because these proteins protect cells from desiccation, oxidative stress, and DNA damage, they have attracted interest as potential therapeutics to enhance stress resilience in other organisms. However, most studies have relied on cultured cells or germline expression, leaving their effects in somatic tissues largely unexplored. Here, we generated Caenorhabditis elegans strains expressing four tardigrade intrinsically disordered proteins, Damage Suppressor (DSUP), cytoplasmic-abundant heat-soluble (CAHS), mitochondrial-abundant heat-soluble (MAHS), and Ramazzottius varieornatus late embryogenesis abundant (RvLEAM), throughout somatic tissues. Surprisingly, constitutive expression of each protein reduced lifespan, impaired motility and reproduction, and failed to improve resistance to most environmental stressors. DSUP toxicity was tissue- and developmental stage-dependent, indicating that both spatial and temporal expression influence its physiological effects. Despite these detrimental phenotypes, several proteins reduced protein aggregation during desiccation-associated stress, demonstrating context-dependent protective effects. Together, our findings reveal that tardigrade stress proteins impose physiological tradeoffs in vivo and underscore the importance of evaluating candidate stress-protective proteins in physiologically relevant somatic models before therapeutic translation.
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BibTeX
@misc{entin2026expression,
title = {{Expression of tardigrade intrinsically disordered proteins in C. elegans reveals variable effects on aging and stress}},
author = {A. Entin and D. Hicks and E. A. Roditi and J. Kim and A. J. Coakley and A. Hruby and A. Alcala and N. Dutta and M. Averbukh and S. Parihar and R. Aviles Barahona and T. J. Lee and V. Kuo and V. Sahasrabuddhe and B. V. Thapa and J. D. Kraft and P. J. Mullen and G. Garcia and R. Higuchi-Sanabria},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.762026},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.762026v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Expression of tardigrade intrinsically disordered proteins in C. elegans reveals variable effects on aging and stress
AU - A. Entin
AU - D. Hicks
AU - E. A. Roditi
AU - J. Kim
AU - A. J. Coakley
AU - A. Hruby
AU - A. Alcala
AU - N. Dutta
AU - M. Averbukh
AU - S. Parihar
AU - R. Aviles Barahona
AU - T. J. Lee
AU - V. Kuo
AU - V. Sahasrabuddhe
AU - B. V. Thapa
AU - J. D. Kraft
AU - P. J. Mullen
AU - G. Garcia
AU - R. Higuchi-Sanabria
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.762026
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.762026v1
AB - Tardigrades survive extreme environmental stress by expressing intrinsically disordered proteins that stabilize cellular structures during cryptobiosis. Because these proteins protect cells from desiccation, oxidative stress, and DNA damage, they have attracted interest as potential therapeutics to enhance stress resilience in other organisms. However, most studies have relied on cultured cells or germline expression, leaving their effects in somatic tissues largely unexplored. Here, we generated Caenorhabditis elegans strains expressing four tardigrade intrinsically disordered proteins, Damage Suppressor (DSUP), cytoplasmic-abundant heat-soluble (CAHS), mitochondrial-abundant heat-soluble (MAHS), and Ramazzottius varieornatus late embryogenesis abundant (RvLEAM), throughout somatic tissues. Surprisingly, constitutive expression of each protein reduced lifespan, impaired motility and reproduction, and failed to improve resistance to most environmental stressors. DSUP toxicity was tissue- and developmental stage-dependent, indicating that both spatial and temporal expression influence its physiological effects. Despite these detrimental phenotypes, several proteins reduced protein aggregation during desiccation-associated stress, demonstrating context-dependent protective effects. Together, our findings reveal that tardigrade stress proteins impose physiological tradeoffs in vivo and underscore the importance of evaluating candidate stress-protective proteins in physiologically relevant somatic models before therapeutic translation.
SN - 2692-8205
ER -