New study maps aging markers in dogs and investigates stem cell therapies, prompting discussion on translational relevance and rigor.
As the geroscience field leans ever more heavily on models that reflect the complexity of human aging, researchers are turning to our closest non-human companions – not for comfort, but for clarity. A new study published in Communications Biology brings together genomics, proteomics and metabolomics to construct a layered aging atlas in dogs, examining immune cell senescence and the effects of a novel stem cell therapy in canines of varying ages [1].
The paper combines single-cell RNA sequencing of peripheral blood mononuclear cells with serum metabolomics and stem cell modelling, tracing both the systemic and cellular signatures of aging in 19 dogs of four breeds. The results point to nine conserved CD8+ T cell senescence markers and identify two metabolites – Penitrem A and UDP-N-acetylglucosamine – as robust markers of aging at both the individual and cellular level. These findings are not just species-specific curiosities; they add momentum to the case for dogs as a highly relevant model for human aging, particularly when it comes to immune system decline, metabolic reprogramming and the quest for clinically meaningful biomarkers.
Longevity.Technology: There’s something reassuring about the fact that man’s best friend is not only sharing our homes and our habits – but also our molecular hallmarks of aging. This multi-omics deep dive into the canine aging process is more than just an exercise in translational biology; it’s a timely reminder that companion dogs, with their accelerated lifespans and overlapping immunometabolic trajectories, are more than endearing stand-ins for human healthspan research – they may be among our most pragmatic models. The identification of conserved CD8+ T cell markers across species is particularly satisfying – not because it’s surprising, but because it adds weight to a growing consensus in the field: that the immune system’s decline is among the more reliable signatures of biological aging, and perhaps, in time, one of the more addressable.
Equally compelling is the metabolomic mapping that throws up UDP-N-acetylglucosamine and Penitrem A as dual-level sentinels of senescence – present both systemically and at the cellular level – as though aging had carelessly left its fingerprints all over the crime scene. It’s hard not to admire the elegance of that discovery. And while dogs won’t be replacing mice in regulatory pipelines any time soon, their value lies precisely in their messiness – the real-world variables of breed, activity, environment and diet mirror our own far more closely than anything found in a pathogen-free vivarium. This paper is a welcome nudge that we may need to rethink our ‘gold standard’ models; sometimes, the right research companion has four legs and might teach us some new tricks.
Immune aging and metabolic drift
The researchers identified nine cell types in the canine blood that change significantly with age, including multiple T cell and myeloid populations. Four of these showed aging patterns consistent with human data, particularly CD8+ T cells, which carried nine conserved senescence markers – five of which were mitochondrial genes, pointing to energy metabolism as a shared driver of decline [1].
Serum metabolomic profiling revealed 51 age-associated metabolites, with UDP-N-acetylglucosamine and Penitrem A increasing across both MSCs and serum samples [1]. These molecules induced canonical features of cellular senescence in vitro – elevated β-galactosidase, suggested reduction in mitochondrial membrane potential, and raised p16 and p53 expression.
To provide a practical framework, the authors proposed a multi-layered aging assessment system – integrating blood counts, biochemistry and metabolomics – as a tool for monitoring both biological age and therapeutic responses. It is a model that aligns with current calls for scalable, real-world diagnostic tools in human longevity medicine.
Gene-edited stem cells under scrutiny
Twelve dogs in the study received mesenchymal stem cells – some modified to overexpress NMNAT1, an enzyme central to NAD+ biosynthesis – as an intervention. According to the authors, this treatment improved biochemical markers associated with liver and kidney function, restored immune balance and appeared to reduce aging-associated metabolic signatures in blood [1].
A metabolomics-based scoring system appeared to demonstrate that while unmodified MSCs slowed aging-associated changes, NMNAT1-enhanced cells achieved partial reversal of key metrics, including suppression of Penitrem A and UDP-N-acetylglucosamine [1].
However, not everyone is convinced by the strength of these claims. Dr Matt Kaeberlein, Professor of Pathology at the University of Washington and Co-Director of the Dog Aging Project, told us that the discovery of novel biomarkers that correlate with age and/or health is useful for a couple of reasons.
“First, these biomarkers may inform us about biological mechanisms underlying the aging process. Second, if they are robust and reproducible, they can be used to predict which interventions are likely to have benefits on lifespan and healthspan more rapidly than would be possible otherwise and at the individual level.”
However, he expressed concerns about how far the findings can be taken.
“The results of this study are overstated,” Kaeberlein told Longevity.Technology. “Particularly the statement in the abstract that ‘it is demonstrated that mesenchymal stem cells, particularly those overexpressing NMNAT1, can delay or reverse aging in dogs’ is false. Just because a small subset of biomarkers are reverted to a level found in younger animals does not prove – or even strongly support – the idea that aging has been delayed or reversed, in the absence of validation that tissue, organ, and whole animal health has been improved.
“Even then, to claim that aging has been reversed would require demonstrating that most – optimally all – phenotypes of aging are reversed. Frankly, the peer-review process failed in this case, as it has quite often recently in other high-profile papers, as such claims do a disservice to the entire field.”
Dogs as translational proxies
Despite those caveats, Kaeberlein remains a strong advocate for companion animals in aging science.
“Companion dogs – and other companion animals – hold great promise as translational models in geroscience,” he told us. “They can inform us about mechanisms of human aging as well as interventions, environmental factors, and genetic variants that are likely to impact human healthspan and longevity.
“Because companion dogs age about 7–10 times faster than people do, it is possible to determine which interventions most effectively increase healthspan and lifespan in a timeframe that is about 7–10 times shorter than would be required in humans.”
With their shared environments, spontaneous disease profiles and genetic diversity, dogs present a more realistic – if messier – model of human aging than traditional lab animals. Their inclusion in longitudinal trials, such as the Dog Aging Project, has already begun to yield insights into environmental exposures, genetic variance and intervention response.
The question, then, is not whether dogs are useful in aging research – but how best to interpret the data they give us. Translational ambition must be matched with analytical rigor. Companion animals may indeed help us trace the shape of aging more clearly – but we must resist the temptation to mistake early signals for destination.
[1] https://link.springer.com/article/10.1038/s42003-025-08333-z
Main photograph: Lifeonwhite/Envato
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