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Effects of Aging, Long-Term and Lifelong Exercise on the Urinary Metabolic Footprint of Rats.

ABSTRACT: Life expectancy has risen in the past decades, resulting in an increase in the number of aged individuals. Exercise remains one of the most cost-effective treatments against disease and the physical consequences of aging. The purpose of this research was to investigate the effects of aging, long-term and lifelong exercise on the rat urinary metabolome. Thirty-six male Wistar rats were divided into four equal groups: exercise from 3 to 12 months of age (A), lifelong exercise from 3 to 21 months of age (B), no exercise (C), and exercise from 12 to 21 months of age (D). Exercise consisted in swimming for 20 min/day, 5 days/week. Urine samples collection was performed at 3, 12 and 21 months of life and their analysis was conducted by liquid chromatography-mass spectrometry. Multivariate analysis of the metabolite data did not show any discrimination between groups at any of the three aforementioned ages. However, multivariate analysis discriminated the three ages clearly when the groups were treated as one. Univariate analysis showed that training increased the levels of urinary amino acids and possibly protected against sarcopenia, as evidenced by the higher levels of creatine in the exercising groups. Aging was accompanied by decreased levels of urinary amino acids and signs of increased glycolysis. Concluding, both aging and, to a lesser degree, exercise affected the rat urinary metabolome, including metabolites related to energy metabolism, with exercise showing a potential to mitigate the consequences of aging.

SUBMITTER: Tzimou A

PROVIDER: S-EPMC7760742 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Effects of Aging, Long-Term and Lifelong Exercise on the Urinary Metabolic Footprint of Rats.

Tzimou Anastasia A Nikolaidis Stefanos S Begou Olga O Siopi Aikaterina A Deda Olga O Taitzoglou Ioannis I Theodoridis Georgios G Mougios Vassilis V

Metabolites 20201125 12

Life expectancy has risen in the past decades, resulting in an increase in the number of aged individuals. Exercise remains one of the most cost-effective treatments against disease and the physical consequences of aging. The purpose of this research was to investigate the effects of aging, long-term and lifelong exercise on the rat urinary metabolome. Thirty-six male Wistar rats were divided into four equal groups: exercise from 3 to 12 months of age (A), lifelong exercise from 3 to 21 months o ...[more]

PMID: 33255518

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Project description:Age-associated chronic basal inflammation compromises muscle mass and adaptability, but exercise training may exert an anti-inflammatory effect. This investigation assessed basal and exercise-induced inflammation in three cohorts of men: young exercisers [YE; n = 10 men; 25?±?1 yr; maximal oxygen consumption (V?o2max), 53?±?3 mL·kg-1·min-1; quadriceps area, 78?±?3 cm2; means?±?SE], old healthy nonexercisers (OH; n = 10; 75?±?1 yr; V?o2max, 22?±?1 mL·kg-1·min-1; quadriceps area, 56?±?3 cm2), and lifelong exercisers with an aerobic training history of 53?±?1 yr (LLE; n = 21; 74?±?1 yr; V?o2max, 34?±?1 mL·kg-1·min-1; quadriceps area, 67?±?2 cm2). Resting serum IL-6, TNF-?, C-reactive protein, and IGF-1 levels were measured. Vastus lateralis muscle biopsies were obtained at rest (basal) and 4 h after an acute exercise challenge (3 × 10 repetitions, 70% 1-repetition maximum) to assess gene expression of cytokines [IL-6, TNF-?, IL-1?, IL-10, IL-4, interleukin-1 receptor antagonist (IL-1Ra), and transforming growth factor-? (TGF-?)], chemokines [IL-8 and monocyte chemoattractant protein-1 (MCP-1)], cyclooxygenase enzymes [cyclooxygenase-1 and -2 (COX-1 and COX-2, respectively), prostaglandin E2 synthases [microsomal prostaglandin E synthase 1 (mPGES-1) and cytosolic prostaglandin E2 synthase (cPGES)] and receptors [prostaglandin E2 receptor EP3 and EP4 subtypes (EP3 and EP4, respectively), and macrophage markers [cluster of differentiation 16b (CD16b) and CD163], as well as basal macrophage abundance (CD68+ cells). Aging led to higher (P ? 0.05) circulating IL-6 and skeletal muscle COX-1, mPGES-1, and CD163 expression. However, LLE had significantly lower serum IL-6 levels (P ? 0.05 vs. OH) and a predominantly anti-inflammatory muscle profile [higher IL-10 (P ? 0.05 vs. YE), TNF-?, TGF-?, and EP4 levels (P ? 0.05 vs. OH)]. In OH only, acute exercise increased expression of proinflammatory factors TNF-?, TGF-?, and IL-8 (P ? 0.05). LLE had postexercise gene expression similar to YE, except lower IL-10 (P ? 0.10), mPGES-1, and EP3 expression (P ? 0.05). Thus, although aging led to a proinflammatory profile within blood and muscle, lifelong exercise partially prevented this and generally preserved the acute inflammatory response to exercise seen in young exercising men. Lifelong exercise may positively impact muscle health throughout aging by promoting anti-inflammation in skeletal muscle.NEW & NOTEWORTHY This study assessed a unique population of lifelong aerobic exercising men and demonstrated that their activity status exerts an anti-inflammatory effect in skeletal muscle and circulation. Furthermore, we provide evidence that the inflammatory response to acute exercise is dysregulated by aging but preserved with lifelong exercise, which might improve skeletal muscle resilience to unaccustomed loading and adaptability into late life.

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Project description:The preventive effects of regular exercise on obesity-related health problems are carried over to the non-exercise detraining period, even when physical activity decreases with aging. However, it remains unknown whether regular childhood exercises can be carried over to adulthood. Therefore, this study aimed to investigate the effects of long-term childhood exercise and detraining on lipid accumulation in organs to prevent obesity in adulthood. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as obese animals. OLETF rats were allocated into sedentary and exercise groups: exercise from 4- to 12-week-old and detraining from 12- to 20-week-old. At 12-week-old immediately after the exercise period, regular exercise completely inhibited hyperphagia, obesity, enlarged pancreatic islets, lipid accumulation and lobular inflammation in the liver, hypertrophied adipocytes in the white adipose tissue (WAT), and brown adipose tissue (BAT) whitening in OLETF rats. Additionally, exercise attenuated the decrease in the ratio of muscle wet weight to body weight associated with obesity. Decreased food consumption was maintained during the detraining period, which inhibited obesity and diabetes at 20-week-old after the detraining period. Histologically, childhood exercise inhibited the enlargement of pancreatic islets after the detraining period. In addition, inhibition of lipid accumulation was completely maintained in the WAT and BAT after the detraining period. However, the effectiveness was only partially successful in lipid accumulation and inflammation in the liver. The ratio of muscle wet weight to body weight was maintained after detraining. In conclusion, early long-term regular exercise effectively prevents obesity and diabetes in childhood, and its effectiveness can be tracked later in life. The present study suggests the importance of exercise during childhood and adolescence to inhibit hyperphagia-induced lipid accumulation in metabolic-related organs in adulthood despite exercise cessation.

Dataset Information

Effects of Aging, Long-Term and Lifelong Exercise on the Urinary Metabolic Footprint of Rats.

Publications

Effects of Aging, Long-Term and Lifelong Exercise on the Urinary Metabolic Footprint of Rats.

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