3.2.3. Mitochondria

Mitochondria are highly adaptive organelles and dynamically respond to environmental stimuli, such as nutritional states and physical exercise. Growth of mitochondrial mass, achieved by mitochondrial biogenesis, is regulated by a number of molecules including the co-transcriptional factor peroxisome-proliferator-activated receptor γ co-activator-1 α (PGC-1 α) [159]. Conversely, mitochondrial mass can be reduced by mitophagy, a process contributing to clearance of defective mitochondria and thus to mitochondrial quality control. Mitochondrial numbers are, furthermore, regulated by mitochondrial dynamics (i.e., fusion and fission) [160] that do not necessarily change mitochondrial mass. Physical activity is known to boost mitochondrial biogenesis and turnover, as well as respiration [161] and mitochondrial quality is positively associated with physical performance [162–164]. AMP-activated protein kinase (AMPK) regulates PGC-1 α [165] and mitochondrial quality control [166] and is therefore an important mediator of mitochondrial biogenesis by PA. Mitochondrial functions, such as for example ATP production, are compromised in advanced age [167]. Accordingly, aging is also associated with oxidative stress and with inflammation [168], as well as with impaired mitochondrial biogenesis. The latter is at least in part mediated by reduced AMPK activity with increasing age [169], an effect that can be prominently attenuated in the skeletal muscle by exercise [170].

**Figure 4.** Mechanisms potentially contributing to the less fatigability of skeletal muscles in females. Modified according to Hunter [158].

> Although sex dimorphisms of mitochondria have been described, they are still a matter of debate and the functional consequences are not well understood. In aged rat brain a higher mitochondrial mass has been reported in males, while females had more efficient mitochondria with a better redox balance, which was in line with reduced levels of uncoupling proteins (UCP4 and UCP5) that are implicated in oxidative stress reduction [165]. This sexual mitochondrial dimorphism may be associated with higher life span and protection from some age-related neurological diseases [171]. Similarly, more efficient mitochondria in female rats have been described in the liver [172,173], cardiac muscle [174] and skeletal muscle [175]. A review of sex-related differences in mitochondria by Ventura-Clapier and colleagues [176] provides an overview on several further rodent studies in which mitochondria of female in most tissues appear to be more efficient and less affected by oxidative stress as compared to males [176]. On the other hand, the transcription of mitochondrial biogenesis-related factors has been reported to be tissue-specifically different in mice; with no differences in the liver but higher levels of related RNAs in brain and kidney of male as compared to female mice [177]. In humans, mitochondrial biogenesis could be higher in blood of females than in blood of men [178]. Conversely, ATP production rates in skeletal muscles have been observed to be lower in women than in men in another study [179].

> In conclusion, the sex dimorphism of mitochondria appears to vary between cell types, tissues and species, as well as with age and health or physical fitness status. To better understand sex-related differences in terms of for example mitochondrial ATP production, reactive oxygen species (ROS)-production/oxidative stress or mitochondrial biogenesis and in particular functional consequences require more detailed research. However, the importance of mitochondrial integrity and efficiency for human health is well established

and mitochondrial quality and biogenesis can be enhanced, e.g., by PA, in both men and women [180–182]. Figure 5 depicts the pleiotropc effects of physical exercise and nutrition on physiology of master's athletes.

Ė **Figure 5.** Pleiotropic effects of physical exercise and nutrition on healthy aging. The right side depicts effects of aging on endocrine function, appetite regulation, glucose metabolism, body composition and mitochondria. The left side illustrates how physical exercise can potentially mitigate effects of aging on the human body of masters athletes. *↑*, positive change; *↓*, negative change; ?, unknown effect. Cholecystokinine, CCK; growth hormone, GH; insulin-like growth factor, IGF.

#### **4. Nutritional Considerations for Masters Athletes**

Masters athletes are often considered as a role model for successful aging and their physical capacities provide useful insight into strategies for healthy aging [183]. Although training is the primary stimulus for exercise-induced adaptations, nutrition can have a major impact on the physiological adaptations that result from exercise training and competition. However, nutrition for the older athletes needs to consider the physiological and diet-related challenges associated with aging and exercise (e.g., changing gu<sup>t</sup> function and nutrient requirements with age) that affect training capacity or nutrient absorption. The most important challenges that masters athletes may face to stay competitive is, first, the maintenance of energy balance, including the risk of low energy availability and, second, anabolic resistance, where the synthetic response to muscle contraction and/or protein ingestion is blunted. For example, a protein-energy deficit can quickly lead to a loss of muscle mass, strength and function together with a transient depression of immune function so that exercise performance is compromised [184]. Furthermore, changes in body composition and hormones in the andropausal/menopausal transition can influence both muscle and bone. The aging muscle is a significant predictor for falls and fractures. Immobilization of a limb due to injury results in a sudden and dramatic muscle wasting and bone loss in conjunction with an inflammatory response, both of which may have detrimental metabolic and functional consequences. This section therefore highlights nutritional aspects that may support health and physical performance for older athletes. Key nutrition-related concerns include the need for adequate energy and protein intake

for preventing low bone and muscle mass and a higher demand for specific nutrients (e.g., vitamin D and probiotics) that may reduce the inflammatory burden in masters athletes. In older adults, gu<sup>t</sup> microbiota composition may represent a marker of health status and probably a predictor of functional decline. With this review, we highlight important research findings on the association between exercise, nutrition and the microbiota, which represents a rapidly developing field in sports nutrition.

#### *4.1. Dietary Protein and Energy Requirements*

It is well known that a balanced diet that provides enough energy to allow physical exercise is of utmost importance to stay healthy, and this is a ye<sup>t</sup> more crucial factor for athletes with specific dietary needs. In sports nutrition, energy availability is defined as the energy available to promote good health once the energy cost of exercise is deducted from energy intake, relative to an athlete's fat-free mass. Low energy availability (<30 kcal/kg of lean body mass/day) is associated with a number of disorders seen in both female and male athletes, including reduced metabolic rate, hormonal changes (e.g., satiety hormones, reproductive hormones, GH and IGF-1), poor bone health and impairments of muscle protein synthesis, immune health and performance [185,186]. Females may have special or different needs due to differences in body size and nutritional status (e.g., energy availability or iron status) as well as due to fluctuations in sex steroid hormones, for example via menopause [187]. Furthermore, physiological changes associated with aging per se such as a gradual decrease in lean body mass and subsequently in RMR, loss of appetite, changes in the composition and function of the gu<sup>t</sup> microbiota but also diminished salivary secretion may increase the risk of inadequate energy intake and might require modification of the master athletes' diet [188]. Although regular PA may lower the risk of inadequate energy intake and has the potential to maintain muscle mass and RMR with aging [46,48], recent findings including athletic populations sugges<sup>t</sup> that masters athletes are still at risk of nutritional deficit [189]. In this study in master triathletes, post-exercise energy and protein intakes relative to body mass were significantly lower than the recommended dietary allowance (RDA) for younger athletes, with −40% for energy (22.7 kJ/kg), and −25% for protein (19.6 g), which may affect post-exercise recovery. Furthermore, dietary analysis revealed that female masters athletes in particular consumed significantly less carbohydrates (0.7 g/kg) post-exercise than recommended (1.0 to 1.2 g/kg).
