Mothers Pass Oxidative Stress Resistance to Offspring in Long-Lived Fruit Flies

In the quiet laboratories of the University of Mysore, a strain of fruit fly has been quietly defying one of biology’s most stubborn rules: that lifespan, however variable, is largely a fixed property of the genome. The long-lifespan line of Drosophila melanogaster isolated there decades ago lives far longer than ordinary laboratory flies, and new research now shows that the biochemical armor that protects these flies from oxidative stress is not merely a private possession of the long-lived genotype. It is passed on to offspring, and the mother’s genetic makeup, not the father’s, largely determines how well the next generation withstands a toxic oxidative assault.

The new study, published in the journal Biogerontology by S. Deepashree and T. Shivanandappa, tackles a question that has lingered at the edge of aging research for years. Oxidative stress resistance is widely regarded as a key contributor to extended longevity, but whether this trait can be transmitted across generations, and by what mechanism, has remained poorly understood. Epigenetic inheritance, the passage of traits through mechanisms other than DNA sequence, has been demonstrated for environmental stress responses in organisms ranging from nematode worms to plants, but its role in the longevity phenotype of Drosophila has been largely unexplored. The Mysore team set out to fill that gap using a rigorous experimental design: reciprocal crosses between a normal-lifespan strain and the long-lifespan strain, followed across three generations.

Reciprocal crossing is the crucial trick here. By mating normal-lifespan males with long-lifespan females, and separately long-lifespan males with normal-lifespan females, the researchers produced offspring that carry essentially the same nuclear genes in both cases but differ in the cytoplasmic and maternal environment they inherit. Any consistent difference between the two reciprocal F1 hybrids cannot be explained by nuclear genotype alone. It points instead to the maternal lineage, whether through the egg’s cytoplasm, its mitochondria, or epigenetic marks laid down during oogenesis. The team then tracked survival, locomotor performance, and antioxidant defenses through the F1 and F2 generations, exposing flies at each stage to paraquat, a herbicide that generates superoxide radicals and is a standard laboratory probe for oxidative stress resistance.

The baseline difference was stark. Long-lifespan flies tolerated paraquat exposure far better than their normal-lifespan counterparts, and within both strains, females were more resistant than males, consistent with earlier work from the same group showing sex differences in oxidative stress defense. But the reciprocal crosses revealed something more intriguing. Female offspring of long-lifespan mothers and normal-lifespan fathers survived paraquat challenge with significantly lower mortality than female offspring of the opposite cross, and this maternal advantage persisted into the F2 generation. The effect was sex-specific: it appeared clearly in daughters but not in sons, suggesting that the maternal transmission of stress resistance interacts with the offspring’s own sex-specific physiology.

Locomotor resilience emerged as the most robust maternally inherited trait of all. Fruit flies instinctively climb upward when tapped to the bottom of a vial, a behavior measured as negative geotaxis, and paraquat exposure degrades this performance as oxidative damage accumulates in the nervous system. The researchers found that the offspring of long-lifespan mothers recovered locomotor function under oxidative challenge better than offspring of normal-lifespan mothers, and this advantage appeared in both sexes and in both the F1 and F2 generations. Narrow-sense heritability estimates for negative geotaxis in males provided a quantitative measure of this differential transmission through mothers, confirming that the maternal contribution to locomotor resilience is a genuine, measurable heritable component rather than a statistical artifact.

Among the biochemical defenses the team measured, glutathione stood out as the most consistent transgenerational maternal antioxidant trait. Glutathione is the cell’s principal endogenous antioxidant, a tripeptide that neutralizes reactive oxygen species directly and feeds the enzymatic systems that detoxify peroxides. Offspring of long-lifespan mothers had significantly higher glutathione levels than offspring of normal-lifespan mothers, in both sexes and in both the F1 and F2 generations. Most strikingly, the F2 generation showed positive recombination values for glutathione, indicating not just persistence of the maternal effect but transgenerational amplification of glutathione-based antioxidant capacity. The biochemical legacy of the long-lived mother, in other words, grows stronger as it passes down the generations.

Catalase told a different story. This enzyme, which breaks down hydrogen peroxide, showed near-zero heritability across the reciprocal crosses, a result the researchers interpret as consistent with catalase’s predominantly nuclear regulation. Because catalase is controlled almost entirely by genes in the cell nucleus, its expression is determined by the offspring’s own genotype rather than by anything the mother contributes through the egg. The contrast between glutathione and catalase is therefore highly informative: it suggests that the maternally inherited component of stress resistance is not a blanket enhancement of all antioxidant systems, but a specific, trait-dependent transmission that favors cytoplasmic and non-nuclear mechanisms.

Variance partitioning analysis reinforced this picture. In the parental generation, the mother’s genotype accounted for prominent contributions to reactive oxygen species levels, lipid peroxidation, superoxide dismutase activity, and locomotor performance. By the F1 and F2 generations, these maternal contributions to the enzymatic and damage markers had diminished, while the effects on locomotion and glutathione persisted. The pattern suggests that the maternal influence on stress resistance is strongest in the traits most closely tied to cytoplasmic inheritance, and that the transmission is selective rather than uniform. Locomotion and glutathione regulation, the authors conclude, are the primary subjects for subsequent studies on the cytoplasmic, epigenetic, and mitochondrial pathways that mediate transgenerational stress resistance.

The implications reach well beyond the fruit fly. If the adaptive stress resistance that underpins extended longevity can be inherited through the maternal line in a trait-dependent fashion, then the search for the genetic and epigenetic architecture of aging must include mechanisms that standard nuclear genetics cannot capture. Mitochondrial DNA, inherited exclusively through the mother in most animals, is an obvious candidate, as are cytoplasmic factors deposited in the egg and epigenetic marks that survive the wave of reprogramming that normally erases them after fertilization. The Mysore team’s long-lifespan strain, isolated decades ago and studied continuously since, has now become a model not just for extended longevity but for the non-genomic channels through which a longevity phenotype can echo across generations. As aging research increasingly embraces the idea that heritability is more than DNA sequence, the humble fruit fly is showing exactly where to look.

Subject of Research: Genetics

Article Title: Oxidative stress resistance of the extended longevity phenotype of Drosophila under paraquat exposure is heritable: influence of maternal genotype on the offspring

Article References: Deepashree, S., & Shivanandappa, T. (2026). Oxidative stress resistance of the extended longevity phenotype of Drosophila under paraquat exposure is heritable: influence of maternal genotype on the offspring. Biogerontology, 27(6), Article 180. https://doi.org/10.1007/s10522-026-10523-z

Image Credits: AI Generated

DOI: 10.1007/s10522-026-10523-z

Keywords: Drosophila, oxidative stress, transgenerational inheritance, maternal effects, longevity, Oxidative, stress, resistance, extended, phenotype, under, paraquat