Part 9 Immune System Series | The Role of Aging, Exercise, and Diet on Immune Function

Key Topics: Inflammation
January 29, 2018 • 4 min read

Exercise and lifestyle throughout life are vital to maintain health over the life span and may reduce the risk of chronic disease.

Aging may be considered a modern pandemic affecting social and financial resources with significant impact. By 2050, 20% of the global population will be 60 years of age or older(Cannata, Marcon et al. 2017) Living longer is a double edge-sword as it brings healthy aging to some and debilitating chronic degenerative diseases affecting many organs to others.

Exercise and lifestyle throughout life are vital to maintain health over the life span and may reduce the risk of chronic disease.(Russell and Lamon 2015) However, older individuals have a reduced capacity to induce muscle hypertrophy with resistance exercise which can lead to sarcopenia.(McGregor, Poppitt et al. 2014) Interestingly, a study of older versus younger men demonstrated a reduced adaptability of aging muscle to exercise as demonstrated by the absence of miRNA regulation and blunted transcription of mRNAs. There is a mechanistic role of miRNA in the adaptation of muscle to anabolic stimulation and it is clear that there is an impairment in exercise-induced miRNA/mRNA regulation with aging.(Rivas, Lessard et al. 2014)

The nutrients in our diet are powerful tools to modulate aging, however, nutrient sensing pathways become deregulated with age and loose effectiveness with age.(Mico, Berninches et al. 2017) MicroRNAs have emerged as important regulators of cellular function and can be modified by diet. Some of the microRNAs target genes encoding proteins and enzymes belonging to the nutrient sensing pathways and may play a major role in the modulation of the aging process. Some of the nutrient sensing pathways impaired by aging play key roles in the regulation of protein synthesis, cell cycle, DNA replication, autophagy, stress response and glucose homeostasis.

There are many biological hallmarks that contribute to aging that include genetic and epigenetic factors, telomere shortening, proteostasis, impaired signaling pathways, reduced stem cell pluripotency, cellular senescence, mitochondrial and immune dysfunction, and alterations in nutrient sensing pathways.(Lopez-Otin, Blasco et al. 2013) In addition, a prominent alteration in intercellular communication with aging is “inflammaging” which is a smoldering proinflammatory phenotype that comes along with getting older. Inflammaging likely has many causes, but at the core of the problem is a failure of the inter-connected immune system (innate and acquired) to effectively resolve the inflammation and return to homeostasis.

Clinical Implications and Relevance in Managing Patient Inflammation with Aging

Given all of the challenges of inflammation associated with aging and infection, what should the cliician do to support healthy aging and reduce chronic inflammatory conditions? Typically, clinicians will prescribe non-steroidal anti-inflammatory drugs to immuno-suppress (block or inhibit) the inflammation pathway. However, use of anti-inflammatory agents may actually prolong the inflammatory tone and cause unwanted side effects such as chronic inflammation. (Serhan 2017).

In addition to healthy diet and lifestyle, there is now an emerging strategy to support the natural pro-resolution pathway via a super-family of chemical mediators that stimulate the resolution of the response, known as specialized proresolving mediators (SPMs). The SPM’s are derived from the diet and are intracellular enzymatic oxidation derivatives of long chain n-3 fatty acids (eicosapentaenoic acid, EPA 20:5n3 and docosahexaenoic acid, DHA 22:6n3), as well as long chain n-6 derived intermediates of arachidonic acid, (AA 20:4n6). Collectively, the SPMs, also called resolvins, are physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. (Wang, Colas et al. 2016; Whelan, Gowdy et al. 2016; Zhu, Wang et al. 2016; Chiang, de la Rosa et al. 2017; Perretti, Cooper et al. 2017)

Additionally, one of the SPMs, resolvin D1 (RVD1) has been shown to engage an RvD1 receptor-dependent regulation of specific miRNA involved in the inflammatory response. RvD1 targets resolvin-regulated miRNAs involved in the inflammatory cascade such as miR-146b (NFκB signaling), miR-219 (targeted 5 lipoxygenase) and reduced leukotriene production. Thus, clinicians may want to recommend n-3 fatty acids to enrich the tissues with EPA and DHA to increase membrane fluidity and to support the resolution of inflammation with resolvins.(Recchiuti, Krishnamoorthy et al. 2011; Recchiuti and Serhan 2012)

Vigilance to a healthy diet and a lifestyle that involves regular exercise continue to be excellent clinical management tools for clinicians that are managing patients with inflammation. The importance of diet is nicely illustrated in animal trials in which vitamin E supplementation reduced atherosclerosis and mortality, but not if the animals were consuming a Western style diet.(Meydani, Kwan et al. 2014) Not only can excellent nutritional quality reduce the incidence of age-related disease, it can also improve the prognosis for age-related disease. Factors that positively and negatively influence nutritional health are nicely illustrated in the Figure adapted from Shlisky et al.(Shlisky, Bloom et al. 2017) Older adults >60y have increased incidence of infectious and inflammatory diseases with prolonged recovery time and higher morbidity and mortality from these diseases. Researchers largely attribute disease onset to immune system dysregulation in which cell mediated immune response is compromised in part through reduced nutritional status and bioactive dietary components (polyphenols, omega-3 long chain fatty acids among others).

An important consideration when evaluating the elderly is the degree of nutritional quality and consumption of nutrient-rich foods. The elderly may have a reduced capacity to absorb and utilize essential nutrients than in their younger years, even without dietary changes. Thus, supplementation of essential nutrients and bioactive components, including bioactive fatty acids, may enhance the function of the immune system and may be an effective strategy to reduce the morbidity and mortality associated with age-related diseases.(Echeverri Tirado and Yassin 2017; Nadjar, Leyrolle et al. 2017; Shlisky, Bloom et al. 2017)

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