FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species

Jiangbo Song, Zhiquan Li, Lei Zhou, Xin Chen, Wei Qi Guinevere Sew, Héctor Herranz, Zilu Ye, Jesper Velgaard Olsen, Yuan Li, Marianne Nygaard, Kaare Christensen, Xiaoling Tong, Vilhelm A. Bohr, Lene Juel Rasmussen () and Fangyin Dai ()
Additional contact information
Jiangbo Song: Southwest University
Zhiquan Li: University of Copenhagen
Lei Zhou: Southwest University
Xin Chen: Southwest University
Wei Qi Guinevere Sew: University of Copenhagen
Héctor Herranz: University of Copenhagen
Zilu Ye: University of Copenhagen
Jesper Velgaard Olsen: University of Copenhagen
Yuan Li: University of Copenhagen
Marianne Nygaard: University of Southern Denmark
Kaare Christensen: University of Southern Denmark
Xiaoling Tong: Southwest University
Vilhelm A. Bohr: University of Copenhagen
Lene Juel Rasmussen: University of Copenhagen
Fangyin Dai: Southwest University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51542-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51542-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51542-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().