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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.

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.

SUBMITTER: Kim DH

PROVIDER: S-EPMC7071238 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.

Kim Dae Hyun DH Bang EunJin E Jung Hee Jin HJ Noh Sang Gyun SG Yu Byung Pal BP Choi Yeon Ja YJ Chung Hae Young HY

Nutrients 20200206 2

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 ha ...[more]

PMID: 32041168

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Project description:Mice and diets. One-month-old male mice of the long-lived B6C3F1 strain were purchased from Harlan (Indianapolis, IN) and maintained as described after weaning (15). Mice were housed in groups of 4 per cage and fed a non-purified diet, PMI Nutrition International Product #5001 (Purina Mills, Richmond, IN). At 5 months of age, the mice were individually housed, and randomly assigned to one of two groups, control (CON) or long-term CR (LTCR). CON mice were fed 93 kcal per week of a defined control diet (AIN-93M, Diet No. F05312, BIO-SERV). LTCR mice were fed 52.2 kcal per week of a defined CR diet (AIN-93M 40% Restricted, Diet No. F05314, BIO-SERV). The LTCR mice consumed approximately 40% fewer calories than mice in the CON mice. The CR diet was enriched so that the CR mice consumed approximately the same amount of protein, vitamins, and minerals per gram body weight as the control mice. Experimental design. At 20 months of age, cohorts of mice in the CON group were randomly assigned to one of 7 experimental groups (Fig. 1). A CON group continued to be fed 93 kcal per week of control diet for 8 weeks. A CR8 group was fed 77 kcal per week of CR diet for 2 weeks, followed by 52.2 kcal per week of CR diet for 6 weeks. The remaining dietary groups were fed the control diets containing, respectively, metformin (MET; Sigma, St. Louis, MO), glipizide (GLIP; Sigma), GLIP plus MET (GM), rosiglitazone (ROS; Avandia, SmithKline Beecham) or soy isoflavone extract (SOY; NOVASOY 400, Life Extension Foundation) for 8 weeks at the dosages indicated in Table 1. The drugs were mixed with powdered control diet and cold-pressed into one gram pellets (BIO-SERV Inc.). At 0900, all mice were fed 2/7 of the weekly allotment of food on Monday and Wednesday and 3/7 on Friday. The mice had free access to acidified tap water. They were fasted for 48 hours and killed by cervical dislocation at 22 months of age. No signs of pathology were detected in the animals used for the studies reported (n=4 per group). Organs were removed rapidly, flash frozen, and stored in liquid nitrogen. The weights of the mice were monitored bi-weekly. Mouse weights are given in Table 1. Measurement of specific mRNA levels. Liver total RNA was isolated as described from livers of pathology-free mice in each group (n=4 per group) (13). mRNA levels were measured using Affymetrix mouse U74Av2 arrays according to standard Affymetrix protocols (Affymetrix). Probe set expression measurement and normalization. After hybridization and scanning, raw image files were converted to probe set data (*.CEL files) using Microarray Suite (MAS 5.0). Probe set data from all 32 arrays were simultaneously analyzed with the Robust multichip Average (RMA) method to generate normalized expression measures for each probe set (Fig. 2; Ref. 24) The data were further filtered to exclude probe data sets that were “Absent” across all 32 arrays according to the MAS 5.0 detection algorithm (1,47). Keywords = CR mimetics Keywords = microarray profiling Keywords = drug discovery Keywords = gene-expression biomarkers Keywords: other

Dataset Information

Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.

Publications

Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.

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