The aging process and the emergence of neurological pathologies span many years in humans. Yet, it is challenging to investigate the initial steps of aging and neurodegenerative processes because most donors of brain samples who exhibit no symptoms are not diagnosed at early stages of disease due to the lack of effective screening. These are some of the main reasons why scientists are turning to short-lived model organisms to study aging.

The Hungarian Canine Brain and Tissue Bank (CBTB) was established by the research team of the Senior Family Dog Project in 2017 to address this need. Although dogs have a much shorter lifespan than humans, the aging process of the two species has remarkable similarities. For instance, dogs tend to develop age-related diseases such as dementia, which is not typical for most other animals.

The ability to detect and predict individual tendencies and provide suitable interventions to shift the aging process to a healthier track is the aim of most aging research initiatives. Dogs mirror human aging at the cellular and molecular levels in many respects, which make them ideal preclinical models and have therefore attracted the attention of aging researchers.

The Hungarian Canine Brain and Tissue Bank (CBTB) was established by the research team of the Senior Family Dog Project in 2017, following the examples of human tissue banks. [Source: Kálmán Czeibert]

“Medical research often relies on laboratory dogs, but keeping them to study natural aging would be time-consuming, expensive, and ethically debatable,” said Sára Sándor, PhD, geneticist and first author on the article published in the journal GeroScience, “Man’s best friend in life and death: scientific perspectives and challenges of dog brain banking.”

Biobanking samples collected and stored from pet dogs, who lived with their owners until being euthanized for medical reasons or old age, provide a valuable resource for aging and other research without the need to include more laboratory animals.

“Pet dogs represent various breeds and live together with their owners. Therefore, we can grasp the effects of lifestyle and environmental stressors on aging and dementia in dogs like in no other model animal,” said Enikö Kubinyi, PhD, principal investigator of the research group. “We realized…linking behavior, pet-keeping conditions, and molecular data would result in a unique biobank.”

[Source: Eniko Kubinyi / Eötvös Loránd University]

Kálmán Czeibert, DVM, PhD, a veterinary anatomist who helped establish the Canine Brain and Tissue Bank said, “The bank currently keeps 130 dog brains and other tissues. Besides continuously upgrading our protocols, we conduct our own studies and are open to sharing the samples with research groups from all over the world.”

Biobanks such as CBTB, where tissues can be stabilized within a few hours after an animal is euthanized, are particularly useful in gene expression studies because RNA molecules are very sensitive and degrade soon after death.

In a recent paper, “CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs,” published in the journal Frontiers in Veterinary Science, the researchers zero in on the expression of the gene CDKN2A (cyclin-dependent kinase inhibitor 2A). The findings that would not have been possible without the CBTB, may augment our understanding of aging processes and the identification of biomarkers of aging.

CDKN2A is a powerful aging biomarker in humans because the expression of this gene progressively increases with age. This correlation is exceptionally high in the brains of older people affected by dementia. Discovering such biomarkers that can signal the onset of age-related diseases before symptoms emerge, is crucial for clinical applications in both dogs and humans.

The researchers examined brain, skeletal muscle, and skin tissue from the donated dogs and found that older dogs also express higher levels of CKDN2A mRNA in their brains and muscles than younger dogs, indicating a positive correlation between CDKN2A expression and age. Interestingly they did not find a similar correlation in the skin. These results, even the inconsistency between tissues, matched previous human findings.

The authors also tested blood samples in live border collies and found a moderate, positive correlation with age even in blood samples. This could have a direct implication in clinical applications.

“This less pronounced correlation means that further research will be required to validate whether CDKN2A could suffice as a blood-borne biomarker for clinical application in dogs,” said Sándor. “However, the robust correlation in the brain shows apparent promises for comparative dementia research because it suggests that similar cellular senescence mechanisms contribute to brain aging in dogs and humans.”

The full potential of such research initiatives could be realized through the longitudinal studies and the banking of high-quality samples of a range of non-invasively and surgically obtained biospecimens.