Fountain of Youth: Understanding inflammaging and why we age

May 12, 2022 - 9 minutes read

Getting older can take a toll on the body. As we age, we may experience more aches and pains, loss of memory, or changes in our vision and hearing. With increasing age, there is also an increased risk of developing chronic diseases. Studies show that nearly 80% of Americans over 65 have at least one chronic disease and 50% have at least two chronic diseases.^[1]

We can see similar changes in our four-legged companions as they age. They begin to slow down, develop cloudy eyes, and their senses start to dull. Aside from these physical changes, dogs may show age-related behavior changes such as having increased anxiety, confusion, disorientation, or changes in their sleep-wake cycle. Giant breed dogs, such as Mastiffs or Great Danes, appear to age faster, becoming seniors as early as 6 or 7, while smaller dogs may not start showing signs of age until they are 9 or 10.

We all want our beloved companions to live forever. If we can better understand how the body ages and why large breed dogs age faster than small breed dogs, we can investigate interventions that may help slow the process of aging. Such interventions could be an anti-aging pill, but they are more likely to include changes in lifestyle through diet, exercise, and the environment.

Why do we age?

For decades, scientists have been studying why we age and how we can slow down the effects. Although aging is a complex process, research suggests that inflammation is at the center. Inflammation is the body’s protective reaction to injury, disease, or irritation. It is usually characterized by signs you might experience if you were to sprain your ankle such as redness, swelling, pain, and heat. Short-term, inflammation can be helpful to fight off microbial invaders or diseases. However, chronic, low-level inflammation can play a role in the development of a host of diseases in humans including type 2 diabetes, heart disease, Alzheimer’s, cancer, and even depression. It is this chronic, sterile (meaning there is no infection to fight off), low-level inflammation that contributes to aging.

What is inflammaging?

Scientists have fittingly coined the chronic, sterile, low-grade inflammation associated with aging inflammaging. The body’s immune-system is complex, consisting of both inflammation preventing (anti-inflammatory) factors and inflammation promoting (pro-inflammatory) factors that are in a delicate balance. As we age, the amount of pro-inflammatory factors increases, tipping the scales to a pro-inflammatory state.

Inflammaging is the result of chronic stimulation of the immune system by various mechanisms. Body composition changes with aging, resulting in increased total body and visceral fat (fat within the abdomen that wraps around organs). Adipose (fatty) tissue releases pro-inflammatory markers that can promote inflammation. In addition, the gut microbiota may contribute to the release of inflammatory products, promoting inflammaging. More information on the gut microbiome can be found in the post entitled Understanding the Microbiome.

How do we measure inflammaging?

As previously mentioned, the immune-system and the process of inflammation is complex. The basic goal is to have white blood cells, the soldiers of our immune-system, get to the area of infection or disease. Here they can ingest foreign materials and cellular debris, destroy infectious agents or cancer cells, or make antibodies. But how do white blood cells know where to go?

Areas that are injured produce messengers called cytokines. Cytokines are small proteins that control the growth and activity of other immune system cells and help recruit white blood cells. Cytokines and related proteins called acute phase proteins can be pro-inflammatory or anti-inflammatory.

Studies in people have shown that levels of pro-inflammatory cytokines and C-reactive protein, a proinflammatory acute phase protein, increase with age and are predictors of mortality in the elderly.^[2] There is evidence that dogs undergo similar inflammaging changes.

To study this in more depth, our research team partners with primary care veterinarians to collect blood samples from dogs in the Precision Cohort. Our labs analyze these samples, measure levels of cytokines as well as inflammatory proteins that are associated with adipose (fatty) tissue. This allows us to develop inflammatory profiles for a wide variety of dogs and compare them between large and small breed dogs.

Why study inflammaging in dogs?

Besides the obvious answer of helping find a way to keep our furry companions around for longer, evaluation of inflammaging in dogs, with their shorter lifespan, offers a unique opportunity to see the effects of aging in a shorter time period. We can study dogs for 10-15 years versus following people for 70-100 years. While dogs age more rapidly than humans, they get many of the same diseases of aging, have a sophisticated health care system comparable to the human health care system, and live in the same environments that we do. By studying dogs, we are not only expanding our knowledge of aging in pets, but also in people.

Here at the Dog Aging Project, we aim to better understand how diet, adiposity (obesity), exercise, environment, and genetics influence health and age-related diseases. Once we understand how our companion dogs age, we can implement nutritional or pharmacological intervention to delay or reduce the effects of aging. As part of our Precision Cohort study, we are evaluating inflammatory markers (cytokines, acute phase proteins, lipoproteins) in dogs to see if they increase with age. The results of these diagnostics will be returned to the Precision cohort participants and their primary care veterinarian. Together, let’s figure out how we can help increase the lifespan of our furry companions!

1. Fontana L. Modulating human aging and age-associated diseases. Biochim Biophys Acta. 2009 Oct;1790(10):1133-8. doi: 10.1016/j.bbagen.2009.02.002. Epub 2009 Feb 10. PMID: 19364477; PMCID: PMC2829866.

2. Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, Cesari M, Nourhashemi F. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013 Dec;14(12):877-82. doi: 10.1016/j.jamda.2013.05.009. Epub 2013 Jun 20. PMID: 23792036.

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