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.

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

“…Previous work of our team on specimens from the same in vivo study revealed aging as the most profound variable compared to exercise on the blood, urine, and fecal sample metabolome, in both sexes. ,− Urine metabolites that belong to amino acids, pyrimidines, and their derivatives were significantly affected by the exercise in both sexes, while amines, alcohols, polyols, alpha hydroxy acids, and carbohydrates were only affected in female rats. , Blood metabolic profiling of exercise training rats demonstrated amino acids, carbohydrates, carboxylic acids, and amines to be subjected to an exercise effect. , The fecal sample metabolome alterations triggered by exercise training were of paramount importance, since compounds from both purine and pyrimidine derivatives, carbohydrate and fatty acid conjugates, amines, amino acids, alcohols, and polyols were significantly changed. Fecal samples were proven to be a more sensitive biospecimen capturing the endogenous response under the exercise training stimulus …”

“…5,23−25 Urine metabolites that belong to amino acids, pyrimidines, and their derivatives were significantly affected by the exercise in both sexes, while amines, alcohols, polyols, alpha hydroxy acids, and carbohydrates were only affected in female rats. 5,25 Blood metabolic profiling of exercise training rats demonstrated amino acids, carbohydrates, carboxylic acids, and amines to be subjected to an exercise effect. 5,24 The fecal sample metabolome alterations triggered by exercise training were of paramount importance, since compounds from both purine and pyrimidine derivatives, carbohydrate and fatty acid conjugates, amines, amino acids, alcohols, and polyols were significantly changed.…”

“…Since rodents share similar molecular mechanisms in disease pathogenesis and present metabolic homogeneity with humans, the relationship between short-term, − chronic (1–6 months), − and single bout exercise to several pathophysiological factors such as obesity, , T2DM, ,, hypertension, heart physiology, , and aging has been investigated using animal models. The effect of lifelong exercise in relation to aging on female , and male , rats has been the focus of our research activities in recent years.…”

Serum metabolomic adaptations following a 12‐week high‐intensity interval training combined to citrulline supplementation in obese older adults

“…Therefore, the changes in the metabolome can be different regarding the modality of exercise intervention. It was previously established that following a 2week sprint interval training in obese men, some metabolic parameters changed significantly immediately after exercise compared to baseline, but these changes were not significant anymore 72 h following the intervention (Tzimou et al, 2020). When comparing the durations, their intervention is considered short-term whereas our intervention is considered long-term (12 weeks).…”

“…Additionally, a recent review reported that metabolite levels can be influenced by nutrition (18). Aging and exercise affect the rat urinary metabolome, and exercise attenuated the consequences of aging (19).…”