Summary: Scientists have identified a protein, OSER1, that appears to play a central role in regulating lifespan. Present across multiple animal species — and detectable in humans — OSER1 emerged from a group of proteins controlled by the longevity-associated transcription factor FOXO. The discovery points to new biological mechanisms behind why some organisms live longer and offers potential targets for therapies that could delay age-related decline.
This discovery suggests OSER1 may be a promising candidate for future treatments designed to extend healthy lifespan or reduce susceptibility to age-related diseases. By clarifying how OSER1 helps cells resist stress and preserves mitochondrial function, researchers aim to translate these findings toward interventions that promote healthier aging.
Key facts:
- OSER1 is an evolutionarily conserved protein linked to increased lifespan in multiple species.
- OSER1 is regulated by FOXO, a well-established longevity transcription factor.
- Manipulating OSER1 levels alters resistance to oxidative stress and affects mitochondrial integrity, energy production, and survival under stress.
- Human proteomic data and genetic variation analyses suggest OSER1 is relevant to human longevity and to cellular stress responses.
- Researchers are pursuing OSER1 as a possible drug target for age-related conditions including metabolic, cardiovascular, and neurodegenerative diseases.
Source: University of Copenhagen
Context: Advice about living longer—sleep, exercise, fasting, social connection and diet—abounds, but the molecular mechanisms that determine lifespan remain an active area of research. A team from the Center for Healthy Aging, Department of Cellular and Molecular Medicine at the University of Copenhagen has identified OSER1 as a previously underappreciated player in longevity pathways.
“We found a protein that can extend lifespan,” says Professor Lene Juel Rasmussen, senior author of the study. “OSER1 is a novel pro-longevity factor that exists across diverse animals, including fruit flies, nematodes, silkworms, and humans.” Because the protein appears in many species, the team believes the findings are likely relevant to human aging.
First author Zhiquan Li explains the rationale: the researchers deliberately focused on proteins conserved between model organisms and humans to increase the chance that discoveries would translate into clinically meaningful results. “If a gene exists only in experimental models, its relevance to human health is uncertain,” Li says. “By screening for longevity-associated proteins shared across species, we aimed to pinpoint candidates that might inform future human therapies and drug discovery.”
How OSER1 was identified and why it matters
OSER1 was discovered while the team screened targets of the FOXO family of transcription factors, a core regulatory hub known to influence aging-related pathways. From a set of candidate genes, ten altered lifespan when their expression was experimentally manipulated. The gene with the strongest and most consistent effect was OSER1.
Experimental evidence across species supports a consistent role for OSER1 in stress resistance and mitochondrial health. In flies, OSER1 overexpression increased resistance to oxidative stress, starvation, and heat shock, whereas reducing OSER1 made flies more vulnerable. Silkworm experiments showed OSER1 both responds to and helps neutralize hydrogen peroxide. In the nematode Caenorhabditis elegans, knocking down OSER1 increased reactive oxygen species (ROS), shortened lifespan, caused mitochondrial fragmentation, lowered ATP production, and altered mitochondrial gene expression.
Human proteomic analysis aligns with these experimental findings: OSER1 appears to be involved in oxidative stress responses, cellular senescence, and reproductive processes. Genetic variation in the OSER1 gene was also associated with human longevity in the cohort analyzed, supporting the idea that OSER1 contributes to lifespan differences in people.
Because reduced lifespan often signals increased risk of premature aging and age-related disease, understanding how OSER1 functions at the cellular and organismal level is crucial. The researchers emphasize that current literature on OSER1 is sparse, and this work is among the first to demonstrate its importance for aging and longevity. Ongoing studies aim to clarify which age-related diseases and biological processes OSER1 most strongly influences.
The team hopes that characterizing OSER1 will reveal new therapeutic targets for age-related conditions, including metabolic disorders, cardiovascular disease, and neurodegeneration. “Identifying this pro-longevity factor brings us closer to understanding the mechanisms that underlie healthy human aging,” says Zhiquan Li.
About this genetics and longevity research news
Author: Sascha Kael
Source: University of Copenhagen
Contact: Sascha Kael – University of Copenhagen
Image: The image is credited to Neuroscience News
Original Research: Open access. “FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species” by Lene Juel Rasmussen et al., published in Nature Communications.
Abstract
FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species
FOXO transcription factors modulate aging-related pathways and influence longevity across species, yet the downstream targets responsible for these effects remain incompletely defined. This study identifies an evolutionarily conserved FOXO target, Oxidative stress-responsive serine-rich protein 1 (OSER1). Overexpression of OSER1 extends lifespan in silkworms, nematodes, and flies, while reduction of OSER1 shortens lifespan. In flies, OSER1 enhances resistance to oxidative stress, starvation, and heat shock; OSER1-deficient flies are more susceptible to these stressors. In silkworms, OSER1 both responds to and helps scavenge hydrogen peroxide in vitro and in vivo. In C. elegans, OSER1 knockdown elevates ROS, leads to shorter lifespan, prompts mitochondrial fragmentation, reduces ATP production, and alters mitochondrial gene transcription. Human proteomic data link OSER1 to oxidative stress responses, cellular senescence, and reproductive biology, with genetic variants in OSER1 associated with human longevity. Together, these results indicate that OSER1 is a conserved FOXO-regulated effector that supports mitochondrial function, enhances stress resistance, and contributes to extended lifespan, warranting further study of its role in healthy aging.