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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.
Kim, DH, Bang, E, Jung, HJ, Noh, SG, Yu, BP, Choi, YJ, Chung, HY
Nutrients. 2020;12(2)
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Low grade, systemic, chronic inflammation is a feature of ageing and underlies many age-related chronic diseases states. As cells age their capacity to proliferate declines, which is referred to as cell senescence. Such senescent cells release multiple inflammatory markers contributing to a pro-inflammatory state. This is further aggravated by elevated oxidative stress and a reduced capacity to manage it, eventually leading to improper gene regulation and DNA damage. To define this age-related, complex inflammatory phenomena the authors introduced the term senoinflammation. A well-established intervention to reverse or slow down the ageing process and many ageing-associated diseases is calorie restriction (CR), by means of reducing overall caloric intake without malnutrition. CR exhibits potent anti-inflammatory effects, reduces age-associated oxidative stress, improves age-related metabolic dysregulation and enhances favourable gene expression. This review summarises how CR and CR-mimicking substances exert their anti-inflammatory effect and some of the cellular mechanism involved and may be of interest to those who are looking to get a more detailed understanding on ageing, inflammation and the benefits of CR.
Abstract
Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.
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Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial.
Itariu, BK, Zeyda, M, Hochbrugger, EE, Neuhofer, A, Prager, G, Schindler, K, Bohdjalian, A, Mascher, D, Vangala, S, Schranz, M, et al
The American journal of clinical nutrition. 2012;96(5):1137-49
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Adipose tissue inflammation is the basis of obesity-related systemic inflammation, which predisposes patients to the development of metabolic and cardiovascular disease. Previous studies show that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduce cardiovascular events and exert anti-inflammatory effects but their effects on human adipose tissue inflammation have so far been unknown. This randomized open-label controlled clinical trial evaluated the effect of an 8-week treatment with n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on adipose tissue and systemic inflammation and on metabolic control. Fifty-five severely obese non-diabetic patients, scheduled for bariatric surgery, were allocated to receive either n-3 PUFAs (n=27) or an equivalent amount of butterfat as control (n=28). Systemic inflammatory markers and metabolic variables were measured at baseline and at the end of the intervention before the participants underwent bariatric surgery. Adipose tissue samples were collected during surgery for the assessment of inflammatory gene expression and lipid mediator production. Treatment with n-3 PUFAs for 8 weeks favourably affected adipose tissue and systemic inflammation. In adipose tissue, the expression of most inflammatory genes was reduced and the concentrations of lipid mediators, responsible for the resolution of inflammation (resolving lipid mediators), were increased. Systemically, the results showed a shift to a more anti-inflammatory plasma fatty acid profile and a decrease in circulating triglyceride levels. The authors concluded that the observed beneficial effects of n-3 PUFAs may be useful in the long-term treatment of obesity.
Abstract
BACKGROUND Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. DESIGN We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. RESULTS Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.
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An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach.
Bakker, GC, van Erk, MJ, Pellis, L, Wopereis, S, Rubingh, CM, Cnubben, NH, Kooistra, T, van Ommen, B, Hendriks, HF
The American journal of clinical nutrition. 2010;91(4):1044-59
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Increasing numbers of the population are overweight or obese, which increases the risk of metabolic diseases such as diabetes and heart disease. Overweight/obese individuals have increased low grade inflammation, which is thought to be an underlying process in disease development. This double blinded randomised controlled trial (RCT) aimed to investigate if dietary supplements could reduce inflammation and oxidative stress. Dietary supplements contained six nutrients (fish oil, green tea extract, resveratrol, vitamin E, vitamin C, and tomato extract) that had evidence of anti-inflammatory properties. Supplements were taken by thirty-six overweight male subjects for five weeks, following a crossover study design. Blood, urine and fat tissue samples were taken as markers of inflammation, oxidative stress and nutrigenomics. Although the main inflammatory marker was unchanged, the study did show a decrease in other inflammatory and oxidative markers, and increase in antiinflammatory markers. The highly sensitive nutrigenomnic measures were able to detect an overall metabolic change. The authors suggested that greater changes might be seen with a longer intervention period. The study showed that supplementation with antiinflammatory food extracts had a beneficial effect on inflammatory and metabolic processes in overweight individuals.
Abstract
BACKGROUND Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. OBJECTIVE It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. DESIGN Dietary products [resveratrol, green tea extract, alpha-tocopherol, vitamin C, n-3 (omega-3) polyunsaturated fatty acids, and tomato extract] selected for their evidence-based antiinflammatory properties were combined and given as supplements to 36 healthy overweight men with mildly elevated plasma C-reactive protein concentrations in a double-blind, placebo-controlled, crossover study with treatment periods of 5 wk. Inflammatory and oxidative stress defense markers were quantified in plasma and urine. Furthermore, 120 plasma proteins, 274 plasma metabolites (lipids, free fatty acids, and polar compounds), and the transcriptomes of peripheral blood mononuclear cells and adipose tissue were quantified. RESULTS Plasma adiponectin concentrations increased by 7%, whereas C-reactive protein (principal inflammation marker) was unchanged. However, a multitude of subtle changes were detected by an integrated analysis of the "omics" data, which indicated modulated inflammation of adipose tissue, improved endothelial function, affected oxidative stress, and increased liver fatty acid oxidation. CONCLUSION An intervention with selected dietary products affected inflammatory processes, oxidative stress, and metabolism in humans, as shown by large-scale profiling of genes, proteins, and metabolites in plasma, urine, and adipose tissue. This trial was registered at clinical trials.gov as NCT00655798.