Helping Animals Live Longer: Targeting the Hallmarks of Aging

Every veterinarian faces the same question: How can we help our patients live longer and happier lives? While we can’t stop time, science is offering exciting new ways to answer this question. Research into the science of longevity is beginning to describe, and hopefully unlock, the specific biological functions that lead to aging. These biological functions have been described as the “hallmarks of aging” and are the key processes that drive age-related degradation of the body. By understanding these hallmarks and how to address them through diet, exercise, lifestyle, veterinary care, supplements, antiaging pharmaceuticals, regenerative medicine, and advances in technology, the veterinary profession has the opportunity to have a greater impact on pet longevity than ever before.

The 9 hallmarks of aging were originally described in Cell in 2013¹ and then were expanded into 12 in 2023 (BOX 1).^2,3 Each of these hallmarks represents processes that, over time, progress and lead to tissue/organ dysfunction, disease, and eventually, age-related death. Understanding these hallmarks and how to slow or potentially reverse these processes is the key to unlocking the puzzle of how bodies age.

Nutrition

As is the case with preventive care in general, one of the most impactful ways to positively affect multiple hallmarks of aging is through nutrition. While the benefits of a healthy diet are nothing new, we are now able to look at diet and dietary ingredients through the lens of longevity and better understand how and why specific nutrients and ingredients promote good health.

Examples of how nutrition impacts longevity include the benefits of antioxidant-rich foods like blueberries and spinach to help combat genomic instability by protecting DNA from damage.⁴ Omega-3 fatty acids found in fish oils reduce chronic inflammation, which is closely linked to cellular senescence.⁵ A well-balanced diet also supports deregulated nutrient sensing by ensuring that pets receive the right amount of calories and nutrients, thereby preventing obesity and metabolic disorders. High-quality proteins in the correct amounts help maintain muscle mass, reducing the risk of degenerative diseases.⁶ Foods rich in coenzyme Q₁₀ (CoQ₁₀), like fatty fish and organ meats, support mitochondrial function, ensuring cells have the energy they need to function properly.⁷ While many other such examples exist, the underlying message is that specific nutrients directly impact the hallmarks of longevity.

Prescription diets such as Purina Neurocare (proplanvetdirect.com) and Hills b/d (hillspet.com) diets utilize the addition of omega 3 fats, medium-chain triglycerides, B vitamins, and antioxidants to promote longevity by supporting cognitive function. The benefits of such purpose-made therapeutic diets with respect to longevity are clear; however, they may be counterbalanced by concerns associated with highly processed kibble.⁸ The relative benefits and drawbacks of well-balanced, fresh, whole-food diets versus kibble and canned extend beyond the scope of this article, although practitioners and pet owners should consider this within the scope of nutrition and longevity.

Exercise

Beyond nutrition, regular exercise is essential for maintaining health as pets age. It supports mitochondrial function by boosting energy production in cells and helps prevent stem cell exhaustion by promoting the regeneration of new cells.⁹ Exercise also helps manage weight, which is crucial for preventing deregulated nutrient sensing. Additionally, regular physical activity promotes the removal of old, damaged cells and encourages the production of new ones, addressing cellular senescence.¹⁰ Whether it’s a daily walk or interactive play with other pets, keeping pets active is among the best ways to promote longevity.

Reduced Stress

Creating a healthy lifestyle is just as important as diet and exercise for pets and their owners. A stress-free, stimulating environment can positively impact epigenetic alterations by keeping a dog’s or cat’s brain active and engaged. A calm and consistent home environment reduces stress, which in turn helps limit altered intercellular communication that can lead to chronic inflammation.^11,12 Healthy, longevity-promoting lifestyle can be promoted through maintaining a regular schedule and providing mental stimulation through toys, training, and social interactions.

Regular Veterinary Checkups

While optimized diet, exercise, and lifestyle are factors largely dependent on the pet owner, the veterinary profession has the opportunity to build these conversations into the larger medical plan to keep patients happy and healthy longer. Regular veterinary checkups are essential for detecting health issues before they become serious, and early detection and treatment can significantly impact several hallmarks of aging.

Veterinarians have the opportunity to positively affect the hallmarks of aging in our patients through what we do and what we don’t do. Routine blood tests such as complete blood counts and chemistries can suggest signs of genomic instability by identifying signs of inflammation and organ dysfunction. Regular dental care helps prevent chronic inflammation that contributes to cellular senescence. Vaccinations and parasite prevention protect pets’ immune system, supporting altered intercellular communication. That said, inappropriate or overuse of vaccines, antibiotics, and other medications, as well as early spay and neuter surgeries, may have equally impactful negative effects on longevity.¹³

Supplements

Another place where veterinarians can provide guidance to pet owners with respect to longevity is advising on supplements. While expertise in supplements is not something every veterinarian would boast, understanding how to use them to a pet’s greatest benefit is valuable knowledge as we promote longevity in patients.

Supplements can play a significant role in targeting specific hallmarks of aging and supporting overall health. For example, NAD+ (nicotinamide adenine dinucleotide) precursors like NMN (nicotinamide mononucleotide) boost mitochondrial function by improving cellular energy production and DNA repair.¹⁴ Antioxidants like resveratrol and CoQ₁₀ protect against genomic instability and loss of proteostasis by reducing oxidative stress and supporting cellular repair mechanisms.¹⁵ Omega-3 fatty acids and joint supplements like UC-II (undentaured type II) collagen help maintain joint health and reduce chronic inflammation.^16,17 By carefully selecting supplements that address a pet’s specific needs, we can help mitigate the effects of aging and support long-term health.

Pharmaceuticals

One of the most dynamic aspects of longevity science is the research of pharmaceuticals that are showing promise in targeting the hallmarks of aging and potentially extending lifespan. Rapamycin, studied in the Dog Aging Project, is a drug that inhibits the mTOR (mammalian target of rapamycin) pathway, promoting autophagy, which can, in turn, reduce chronic inflammation and delay cellular senescence.^18,19 Metformin is being explored for its antiaging effects through AMP (adenosine monophosphate) activation of protein kinase, a cellular energy sensor that mimics the effects of calorie restriction, helping to improve mitochondrial function and reduce metabolic issues associated with deregulated nutrient sensing.^20,21

Senolytic drugs, like quercetin and dasatinib, target and eliminate senescent cells, reducing chronic inflammation, which can promote healthier aging.²² Rather than daily usage, longevity medicine protocols utilizing senolytics such as quercetin and dasatinib are most frequently used for 1 to 3 days anywhere from monthly to quarterly.

While pharmaceuticals specifically targeting the hallmarks of aging are not currently being widely utilized in conventional human or veterinary medicine, they (and others) will likely gain more attention as research continues.

Regenerative Medicine

Stepping beyond pharmaceutical intervention, regenerative medicine offers exciting possibilities for reversing some of the damage caused by aging. Harnessing the body’s natural healing processes, these therapies can address several hallmarks of aging. Stem cell therapy and platelet-rich plasma have been available to veterinary patients for some time, although they may not be utilized to their greatest potential when it comes to promoting longevity. Both of these therapeutics have primarily been used to treat damaged and arthritic joints. Given that stem cell exhaustion, tissue degeneration, and chronic inflammation are all factors that promote aging, it may be that these therapeutics can be used more proactively in a wider variety of patients.

Continuous Patient Monitoring

The future of medical practice, both human and veterinary, will rely heavily on continuous patient monitoring. Wearable devices that monitor heart rate, oxygen saturation, activity, electrocardiography, blood glucose, and more are all commonplace in human medicine. As valuable as these are for humans, the potential applications for an entire population of nonverbal patients promise to change how veterinary medicine is practiced. Wearable devices have the potential to alert pet owners and veterinarians when animals are showing early signs of disease, rather than diagnoses only being made during a medical crisis. As these technologies continue to evolve, they will likely become even more integrated into veterinary care, offering comprehensive health monitoring and personalized care plans.

Summary

Recent research highlights that aging is a complex, multifaceted process, and the key to extending longevity lies in our deep understanding of the cellular and subcellular mechanisms involved.^3,23-25 Pet owners can promote their pets’ longevity by optimizing lifestyle choices including nutrition, exercise, and proactive medical care. A healthy lifestyle provides a solid foundation upon which veterinarians can build by offering integration of targeted supplements, antiaging pharmaceuticals, regenerative medicine, and wearable technology, allowing pets and their owners access to emerging breakthroughs in longevity science. As groundbreaking longevity-focused therapeutics continue to emerge, veterinarians will be uniquely positioned to take a leading role in not only extending the lifespan but also improving the quality of life for our animal companions.