Physical exercise, 1,25-dihydroxyvitamin D, and prevention of the consequences of ageing. The FIT-AGEING study

Resumen

Ageing is a natural and multi-factorial process that affect human beings as they age, from born to death. At advanced age it is characterized by a progressive decline of physiological integrity leading to impaired physical and cognitive functions, and increasing the incidence of several agerelated diseases. This late deteriorative phase of the ageing process can be named as aging, and the efforts related to prevent or delay the aging process as anti-aging. Recent studies have established the importance of vitamin D status on human’ health during the ageing process beyond its role on specific physiological mechanisms in different organs and systems. In this sense, the main active metabolite of vitamin D, the 1,25-dihydroxyvitamin D (1,25(OH)2D), also known as calcitriol, is responsible for most of its biological effects, and considered a powerful biomarker that plays an important role in ageing-related physiological processes. However, little is known about their possible relationship with other ageing or, more precisely, aging biomarkers in healthy adult population. Furthermore, although previous studies have described that an exercise intervention induces important benefits for human health, the effects of physical exercise on 1,25(OH)2D have not been deeply studied. On the other hand, there is no study comparing the influence of different physical exercise interventions on 1,25(OH)2D. The main aims of this International Doctoral Thesis are to study the relationship of 1,25(OH)2D and body composition, physical activity levels, physical fitness, cardiometabolic health, and the shed form of the Klotho protein (S-Klotho) (Section 1), and to study the effect of different exercise training programs on 1,25(OH)2D (Section 2) in middle-aged sedentary adults. This International Doctoral Thesis includes a total of 5 studies. The present results show that 1,25(OH)2D was negatively associated with body mass index, lean mass index, and bone mineral density (Study 1), while objectively measured sedentary behaviour, physical activity levels, and physical fitness did not seem to be related to 1,25(OH)2D (Study 2). Additionally, no association was found between 1,25(OH)2D and cardiometabolic risk factors or insulin resistance, although an inverse association between 1,25(OH)2D and central adiposity was observed (Study 3). On the other hand, 1,25(OH)2D was negatively associated with S-Klotho plasma levels, which was partially mediated by bone mineral density (Study 4). Finally, a 12-weeks exercise program significantly increased the levels of 1,25(OH)2D regardless of the exercise modality, observing a significant positive association between changes in physical fitness and changes in 1,25 (OH)2D (Study 5). Collectively, the results from the present International Doctoral Thesis enhance our understanding of the relationship of 1,25(OH)2D with several anti-aging factors such as body composition, physical activity levels, physical fitness, cardiometabolic health, and S-Klotho protein in middle-aged sedentary adults. Moreover, it provides novel information regarding the role of different exercise training programs on 1,25(OH)2D, as well as its potential relationship with exercise-induced changes in body composition and physical fitness.