Physical exercise as a modulator of the anti-ageing klotho protein health-related cardiometabolic implications. The fit-ageing study

  1. Amaro Gahete, Francisco J.
Supervised by:
  1. Jonatan Ruíz Ruíz Director
  2. Manuel Joaquín Castillo Garzón Director

Defence university: Universidad de Granada

Fecha de defensa: 12 September 2019

  1. Jesús Rodríguez Huertas Chair
  2. Virginia Aparicio García-Molina Secretary
  3. José Eduardo Galgani Fuentes Committee member
  4. María Carmen Gómez Cabrera Committee member
  5. Ignacio Ara Royo Committee member

Type: Thesis


Since the discovery of the Klotho gene as a suppressor of several ageing phenotypes, numerous studies have focussed on elucidating the molecular pathways that mediate the effects of its expression on cellular ageing-related processes. However, the role of the shed form of the Klotho protein on physical fitness, energy metabolism and cardiometabolic health has not been deeply studied. Moreover, there is a biological base supporting the hypothesis that physical exercise could induce an increment of S-Klotho, resulting in one of the still unrecognized physiological mechanism that can explain the exercise benefits on the ageing process. The main aims of this International Doctoral Thesis are to study the association of S-Klotho with physical fitness, energy metabolism and cardiometabolic health, and to study the effect of different exercise training programs on S-Klotho, as well as on physical fitness, energy metabolism, and cardiometabolic health in sedentary middle-aged adults. The results show that lean mass is strongly associated with S-Klotho and explains the association of physical fitness with S-Klotho. BFox and MFO are positively associated with S-Klotho, whereas S-Klotho is negatively associated with cardiometabolic risk. Moreover, exercise training (specially a HIIT+EMS program) induces an increase of S-Klotho, improves body composition, physical fitness and energy metabolism, and reduces cardiometabolic risk. In summary, the results show that S-Klotho plays a key role on physical fitness, energy metabolism and cardiometabolic health in sedentary middle-aged adults, and that exercise training modulates S-Klotho, as well as physical fitness, energy metabolism and cardiometabolic health. These findings may partially explain some of the unknown exercise-induced effects on cardiometabolic health as well as on the human ageing process.