SPMs and Inflammation in Aging

Intuitively, we understand that our health status declines as we age. Increasing incidence of morbidity associated with chronic diseases leads to reduced mobility in our elder years, which has downstream effects on our mental health and overall quality of life as we age. Research is showing us that many of the chronic conditions associated with aging are actually themselves associated with low-grade systemic inflammation, not resulting from any specific injury. This confluence of health conditions that emerge in advancing age is also termed “inflammaging.”

In this week’s blog post, we delve into the literature surrounding inflammation and aging. We also discuss how supplementation with specialized pro-resolving mediators (SPMs) may resolve age-associated inflammation and lead to more and healthier years toward the end of life.

Inflammation is Related to Several Aging-Associated Conditions

As we age, our immune system produces low-grade pro-inflammatory mediators, which are associated with atherosclerosis, dementia, and diabetes, among other conditions. For example, elevated levels of the inflammatory marker C-reactive protein (CRP), often common in elderly adults, are associated with elevated risk of cardiovascular mortality. Other inflammatory markers such as IL-6 and TNF-α are also related to the above-mentioned comorbidities. Indeed, two- to four-fold elevations in circulating pro-inflammatory cytokines are common among elderly adults, even when the adults are free of any disease.

The causes and outcomes of inflammation in aging are often entangled, making it difficult to tell if age-associated diseases are a cause of inflammation or an effect. Risk factors like obesity, lack of physical activity, mitochondrial damage, epigenetic modification, and oxidative stress have a complex relationship with inflammation and disease outcomes.

While the healthcare system at large tends to treat each aging-related disease separately, research is pointing to the fact that each disease is related to chronic inflammation. A 2013 study published in Cell Metabolism showed that inflammation is causally linked to decline in aging in a mouse model of human disease progression. The study specifically identified insulin-resistance, bone loss, frailty, and cognitive decline as related to inflammation.

Inflammation Resolution for Improved Aging Outcomes

The major financial, physical, and emotional costs of aging-related inflammation have led to a variety of pharmacological interventions to manage disease-specific symptoms and inflammation as a whole. However, many such interventions may come with side effects, complications, and an added financial burden on patients and the healthcare system. Lifestyle interventions like regular exercise may be especially helpful for aging individuals. Exercise, if done regularly, has an anti-inflammatory effect. Maintaining a healthy weight is also an important strategy to reduce inflammation and diseases associated with inflammaging.

Alternatively, supplementing the diet with SPMs is another strategy that can be used to resolve inflammation endemic in aging. Specialized pro-resolving mediators as a category are comprised of lipoxins, resolvins, protectins, and maresins, which have distinct structures but play a similar role in resolution of inflammation.

In a mouse model of aging, researchers found that elderly mice had delayed resolution of inflammation and lower levels of SPMs, compared to healthy control mice. Supplementing the mice’s diets with the omega-3 fatty acid DHA and SPMs promoted active resolution of inflammation endemic in the aging process.

While inflammation is typical in most chronic diseases associated with aging, researchers have also begun to study disease-specific applications of SPMs for inflammation resolution. In conditions as seemingly different as Alzheimer’s disease and arthritis, SPMs have been shown to improve inflammation resolution and improve patient outcomes. Positive inflammation-resolution factors like adherence to a Mediterranean diet, omega-3 fatty acids and SPMs, and physical activity may help to improve the patient outcomes associated with inflammaging.

References

Arnardottir HH, Dalli J, Colas RA, et al. Aging Delays Resolution of Acute Inflammation in Mice: Reprogramming the Host Response with Novel Nano-Proresolving Medicines. The Journal of Immunology. 2014;193(8):4235-4244.

Dalli J. Lipid Mediators and the Resolution of Chronic Inflammation: Implications for Arthritis Therapy. Osteoarthritis and Cartilage. 2016;24(S1):S2.

Fiala M, Terrando N, Dalli J. Specialized Pro-Resolving Mediators from Omega-3 Fatty Acids Improve Amyloid-β Phagocytosis and Regulate Inflammation in Patients with Minor Cognitive Impairment. Journal of Alzheimer’s Disease. 2015;48(2):293-301.

Larbi A, Rymkiewicz P, Vasudev A, et al. The Immune System in the Elderly: A Fair Fight Against Diseases? Aging Health. 2013;9(1):35-47.

Simanek AM, Beam Dowd J, Pawelec G, et al. Seropositivity to Cytomegalovirus, Inflammation, All-Cause and Cardiovascular Disease-Related Mortality in the United States. PLoS One. 2011. 6(2):e16103.

Wang X, Zhu M, Hjorth E, et al. Resolution of Inflammation is Altered in Alzheimer’s Disease. Alzheimer’s & Dementia. 2015. 11(1):40-50.e2.

Woods JA, Wilund KR, Martin SA, Kistler BM. Exercise, Inflammation, and Aging. Aging and Disease. 2012. 3(1):130-140.

Youm Y, Grant RW, McCabe LR, et al. Canonical NIrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging. Cell Metabolism. 2013. 18(4):519-532.

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