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From the Townsend Letter
June 2015

Anti-Aging Medicine
Anti-Aging Insights on Inflammation
by Ronald Klatz, MD, DO, and Robert Goldman, MD, PhD, DO, FAASP
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The body deploys the inflammatory response as a defense mechanism to counter infection. However, unchecked chronic inflammation can be a deleterious process, contributing to conditions from heart disease to irritable bowel syndrome to cognitive decline. Chronic inflammation also reduces the number of vital, healthy years. Vishwa Deep Dixit, from Yale School of Medicine (Connecticut, US), and colleagues identified a compound, known as Nlrp3, as a trigger of aging-related inflammation. The team revealed that this compound causes a loss of function that manifests as insulin resistance, bone loss, frailty, and cognitive decline. The study authors are hopeful that future therapeutics targeted at lowering Nlrp3 might "delay multiple age-related chronic diseases."

Youm Y-H, Grant RW, McCabe LR, et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.
Cell Metab. 2013;18 (4):519–532.

Inflammation and Obesity
The expression of inflammation-associated genes in fat tissue may contribute to obesity. Marjukka Kolehmainen and colleagues  from the University of Eastern Finland assessed a group of obese adults with features of the metabolic syndrome who participated in an 18- to 24-week randomized intervention study comparing a Nordic diet (consisting of whole-grain products, vegetables, root vegetables, berries, fruit, low-fat dairy products, rapeseed oil, and three servings of fish per week) with a control diet (low-fiber grain products, butter-based spreads, and limited intake of fish). Participants were asked to maintain their body weight unchanged during the intervention, and no significant weight changes occurred during the study period. Samples of the participants' adipose tissue were taken at the beginning and end of the study, and a transcriptomics analysis was performed in order to study the expression of genes. The team observed differences in the function of as many as 128 different genes in the adipose tissue of the group consuming the Nordic diet vs. control group. In the Nordic diet group, the expression of several inflammation-associated genes was lower than in the control group. The study authors report: "A healthy Nordic diet reduces inflammatory gene expression in [subcutaneous adipose tissue] compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome."

Kolehmainen M, Ulven SM, Paananen J, et al. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome. Am J Clin Nutr. January 2015;101:228–239.

Inflammation and Sensory Functions
Bioinflammation – the body's response to injury, which may be associated with aging-related concerns from Alzheimer's disease to cancer, may trigger hearing loss.

Michael D. Seidman and colleagues from Henry Ford Hospital (Michigan, US) examined the potential protective mechanism of resveratrol, an antioxidant substance found abundantly in red grapes and red wine, to reduce temporary threshold shifts and decrease cochlear hair cell damage following noise exposure. The team designed a study to identify the potential protective mechanism of resveratrol following noise exposure by measuring its effect on cyclooxygenase-2 (COX-2; key to the inflammatory process) protein expression and formation of reactive oxygen species, which plays an important role in cell signaling and homeostasis. The data revealed that acoustic overstimulation causes a time-dependent upregulation of COX-2 protein expression. And, resveratrol significantly reduces reactive oxygen species formation, inhibits COX-2 expression, and reduces noise-induced hearing loss following noise exposure in rats. Observing that "by giving animals resveratrol, we can reduce the amount of hearing and cognitive decline," the study authors submit that their findings suggest that resveratrol may exert a protective effect from noise-induced hearing loss by the inhibition of COX-2 expression and reactive oxygen species formation.

Seidman MD, Tang W, Bai VU, et al. Resveratrol decreases noise-induced cyclooxygenase-2 expression in the rat cochlea. Otolaryngol Head Neck Surg. 2013 Feb 4.

Inflammation and Mental Health
Elevated levels of C-reactive protein, a marker of inflammatory disease, may be associated with increased risk of psychological distress and depression. Marie Kim Wium-Andersen and colleagues from Copenhagen University Hospital (Denmark) analyzed CRP levels using data from two general population studies in Copenhagen, which included 73,131 men and women aged 20 to 100 years. Increasing CRP levels were associated with increasing risk for psychological distress and depression in analyses. Other analyses suggest that increasing CRP levels also were associated with increasing risk for hospitalization with depression, according to the study results. The study authors conclude: "Elevated levels of [C-reactive protein] are associated with increased risk for psychological distress and depression in the general population."

Wium-Andersen MK, Orsted DD, Nielsen SF, Nordestgaard BG. Elevated C-reactive protein levels, psychological distress, and depression in 73 131 individuals. Arch Gen Psychiatry. Dec. 24, 2012:1–9.

Evidence suggests that certain nutrients and lifestyle choices may serve as effective approaches that may help to curb the chronic inflammatory response.

Look to Nature to Lower Inflammation
"Feel-good" emotions triggered by enjoying nature's great wonders may lower a person's cytokines. Cytokines are proteins that prompt for increased activity of the immune system, a process necessary to combat infection. However, when the mechanism goes into overdrive, it may contribute to heart disease, type 2 diabetes, autoimmune diseases, mood disorders, and more. Jennifer Stellar from the University of California, Berkeley (US), and colleagues completed two separate experiments, enrolling over 200 young adults. Participants reported on a given day the extent to which they had experienced such positive emotions as amusement, awe, compassion, contentment, joy, love, and pride. Samples of gum and cheek tissue, known as oral mucosal transudate, taken that same day showed that those who experienced more of these positive emotions, especially awe, wonder, and amazement, had the lowest levels of the cytokine interleukin 6, a marker of inflammation. Observing that "awe … was the strongest predictor of lower levels of pro-inflammatory cytokines. These effects held when controlling for relevant personality and health variables," the study authors submit: "This work suggests a potential biological pathway between positive emotions and health through proinflammatory cytokines."

Stellar JE, John-Henderson N, Anderson CL, Gordon AM, McNeil GD, Keltner D. Positive affect and markers of inflammation: discrete positive emotions predict lower levels of inflammatory cytokines. Emotion. 2015 Jan 19.

Apple Compounds Abate Inflammation
Apple peel is an abundant source of triterpenoids – plant-based compounds thought to influence expression of IP-10, a gene linked to inflammatory disorders including irritable bowel disease. Elke Richling and colleagues from University of Kaiserslautern (Germany) studied the effects of ursanic, oleanic, and lupanic pentacyclic triterpenoids found in apple peel for their anti-inflammatory effects, using colon cancer cells that were exposed to the triterpenoids and then stimulated with pro-inflammatory cytokines. Finding that the apple peel compounds inhibited the expression of IP-10, the study authors submit: "The present study confirms that triterpenoids present in apple peel … may be implicated in the anti-inflammatory properties of apple constituents, suggesting that these substances might be helpful in the treatment of [irritable bowel disease] as nutrient supplements."

Mueller D, Triebel S, Rudakovski O, Richling E. Influence of triterpenoids present in apple peel on inflammatory gene expression associated with inflammatory bowel disease (IBD). Food Chem. 15 August 2013;139(1–4):339–346.

Inflammation Intervention
Regular exercise may exert physiological changes that decrease inflammation on a local and systemic level. Nicholas Young and colleagues from Ohio State University (US) completed an in vivo study measuring the regulation and activation of NF-kappa-beta, a protein complex that controls many genes involved in inflammation that is found to be chronically active in many inflammatory diseases, in mice. An inflammatory response was created in mice both before and after exercise through an injection of lipopolysaccharides. The impact of exercise was measured over time following the inflammatory response. There was a strong systemic and local inflammatory response upon injection of lipopolysaccharides, which was strongest at 2 hours postinjection. NF-kappa-beta activation was seen as a result of the lipopolysaccharides and was detected in lymphatic tissues throughout the mouse. In those groups where mice were exercised pre- and post-LPS injection, the NF-kappa-beta activation was significantly inhibited in whole-body systemic analysis. The effect of exercise on the inhibition of NF-kappa-beta activation was identified as a transient effect, lasting only 24 hours after exercise. Importantly, the role of exercise in inhibiting NF-kappa-beta activation was linked to the suppression of multiple pro-inflammatory cytokines.           

Young N et al. Abstract #OP0109. Presentation at EULAR 2014 (European League Against Rheumatism). 12 June 2014.

To stay updated on the latest breakthroughs in natural approaches to manage the body's process of inflammation, visit the World Health Network (, the official educational website of the A4M and your one-stop resource for authoritative anti-aging information. Be sure to sign up for the free Longevity Magazine e-journal, your weekly health newsletter featuring wellness, prevention, and biotech advancements in longevity.

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