Dogs Reveal Sex-Specific Immune Aging Patterns and Early Clues on Anti-Aging Drugs

Dogs have long been considered one of the best animal models for studying human aging. They share our homes, our environments, and many of our age-related diseases, and they age several times faster than we do, which makes it possible to observe the arc of a lifetime within a decade. Yet one fundamental aspect of canine aging has remained surprisingly underexplored: how the immune system changes with age in males and females, and whether those changes differ between the sexes. A new study published in the journal Biogerontology by researchers at the Southern University of Science and Technology in Shenzhen and their collaborators set out to fill that gap, mapping immune aging across the canine lifespan and testing how three candidate anti-aging interventions reshape the immune landscape in the short term.

The research team, led by Meiling Lai, Fengge Xu, Yingxia Xu, and senior author Yu-Xuan Lyu, assembled a carefully controlled cross-sectional cohort of 80 intact laboratory Beagles ranging from 1 to 11 years of age. Using a single breed kept under controlled laboratory conditions was a deliberate design choice. Pet dogs vary enormously in diet, exercise, neuter status, and environment, all of which can confound measurements of immune aging. By studying intact animals of one breed across a defined age range, the researchers could isolate the effects of age and sex on blood cell counts and circulating inflammatory signals with unusual clarity.

The first major finding is that canine immune aging is neither uniform nor linear. Several absolute leukocyte counts, meaning the numbers of specific white blood cell types circulating in the blood, did not simply decline steadily with age. Instead, they fell during the middle of the lifespan and then rose again in the oldest, geriatric dogs. This kind of undulating, non-linear trajectory echoes what has been described in human aging research, where large-scale studies of the plasma proteome have revealed waves of molecular change rather than a smooth slope. It suggests that the aging immune system passes through distinct stages, and that measurements taken at a single age may miss the bigger picture.

The serum cytokine data, which capture the levels of signaling proteins that immune cells use to communicate, told an even more interesting story when the researchers split the results by sex. More cytokines varied significantly with age in male dogs than in female dogs, pointing to a sex-stratified pattern of immune aging. This mirrors a growing body of human evidence showing that women and men age immunologically in different ways, with differences in immune cell composition, inflammatory tone, and susceptibility to autoimmune and infectious disease. However, the authors were careful to note a statistical caveat: when they formally tested for age-by-sex interactions and corrected for multiple comparisons using false discovery rate methods, those interaction effects did not remain significant. The sex-stratified patterns are therefore suggestive rather than definitive, and the researchers frame them as a basis for future work rather than a settled conclusion.

Why does this matter for human medicine? The concept of inflammaging, the chronic low-grade inflammation that accumulates with age and contributes to cardiovascular disease, frailty, and other conditions, is a central pillar of modern geroscience. If dogs show their own version of inflammaging, and if that process unfolds differently in males and females, then dogs could serve as a powerful translational model for testing interventions aimed at damping down age-related inflammation. The new study provides the reference map that such interventions will need: a description of what normal immune aging looks like in a controlled canine population, stage by stage, sex by sex.

The second half of the study moved from observation to intervention. The team evaluated 24 young Beagles that received one of three geroprotective treatments for 90 days: rapamycin, canagliflozin, or dietary restriction. Rapamycin, a drug that inhibits the mechanistic target of rapamycin pathway, is perhaps the most intensively studied longevity intervention in laboratory animals, having extended lifespan in mice even when administered late in life. Canagliflozin, a diabetes drug belonging to the SGLT2 inhibitor class, has shown lifespan-extending effects in male mice and is being explored for broader geroprotective properties. Dietary restriction, the reduction of caloric intake without malnutrition, remains the most reproducible intervention for slowing aging across species, with classic studies in dogs showing that lifelong moderate restriction extended lifespan and delayed age-related changes.

After the 90-day intervention window, the three treatments produced clearly different immune and metabolic signatures. Rapamycin was associated with the broadest response across the measured cytokine endpoints, suggesting that mTOR modulation produces wide-reaching shifts in inflammatory signaling even over a relatively short period in young animals. Canagliflozin showed a narrower set of cytokine differences, alongside a descriptive reduction in body weight, hinting that its effects on immune aging may be more targeted. Dietary restriction reduced body weight as expected but did not alter any of the measured immune endpoints within the study window. That last result is notable because it separates the metabolic effects of caloric restriction from its immunological effects, at least on the timescale and endpoints examined here.

The authors are appropriately cautious about these intervention findings. The group sizes were small, with only a handful of dogs per treatment arm, and cytokines were measured only at the endpoint of the study rather than before and after treatment. Without baseline measurements, it is impossible to distinguish true treatment-induced changes from pre-existing differences between groups. The researchers explicitly describe the intervention results as exploratory and hypothesis-generating, a framing that reflects good scientific practice but also underscores how early this line of work remains. Larger, longitudinal trials with baseline sampling will be needed to confirm whether rapamycin’s broad cytokine response represents a genuine geroprotective signature or statistical noise amplified by small numbers.

Even so, the study arrives at a moment of rapid growth in canine geroscience. Large initiatives such as the Dog Aging Project are following tens of thousands of companion dogs to identify biological markers of aging, and a major randomized trial called TRIAD is currently testing rapamycin in healthy middle-aged dogs. Previous smaller trials of short-term rapamycin in companion dogs have suggested effects on immune function and heart health. The new Beagle study complements these efforts by offering a controlled, sex-stratified baseline for immune aging and by providing early comparative data on three distinct geroprotective strategies within a single experimental framework. Because dogs develop many of the same chronic diseases humans do, and share our living environments, positive results in canine trials carry more translational weight than rodent findings alone.

The broader lesson from the study is that aging biology cannot be understood without accounting for sex. Sex differences in lifespan are well documented across mammals, and the immune system is one of the most sexually dimorphic organ systems in the body. By showing that canine cytokine profiles age differently in males and females, even if formal statistical interactions await confirmation in larger cohorts, the study adds dogs to the list of species in which immune aging must be studied separately in each sex. For veterinarians, the stage-specific hematologic changes and sex-stratified cytokine patterns could eventually inform better interpretation of blood tests in aging dogs. For geroscientists, the work lays the groundwork for longitudinal studies that track individual animals over time, measure immune markers before and after intervention, and determine whether short-term molecular responses to drugs like rapamycin predict longer-term gains in healthspan and lifespan. The dogs, as so often, may end up teaching us a great deal about ourselves.

Subject of Research: Sex differences in immune aging and geroprotective intervention responses in dogs

Article Title: Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions

Article References: Lai, M., Xu, F., Xu, Y., Mironenkov, A., Jin, Y., Zhang, S., Pan, J., Li, M., Deng, B., Zhu, J.-K., & Lyu, Y.-X. (2026). Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions. Biogerontology, 27(5), Article 172. https://doi.org/10.1007/s10522-026-10518-w

Image Credits: AI Generated

DOI: 10.1007/s10522-026-10518-w

Keywords: canine aging, immune aging, inflammaging, sex differences, rapamycin, canagliflozin, dietary restriction, geroprotectors, cytokines, Beagle model, geroscience, blood biomarkers