## 4 Discussion and Interpretation
### Body and Tissue Weights (Table 3)
Furthermore, the known implications of SPARC in the functions of erythroid progenitors [74] could suggest that _Sparc_ KO mice would have reduced hemoglobin (low blood cells cancer) and, therefore, reduced oxygen transport ability. This would require one to increase the blood supply to different tissues to compensate low blood oxygenation via increased blood circulation that would require a developed cardiac pump and, thus, explains the increased weight (percentage) of the heart in _Sparc_ KO mice; such low oxygenation further worsens the weak oxidative phosphorylation capacity in SM that _Sparc_ KO mice already have. The other tissues patterns (age- and exercise-dependant) are in accordance with the known effects of both ageing and exercise on diverse tissues. For instance, the increased brain and hypothalamus weight percentages (trend) with exercise fits with the ability of exercise to enhance neurogenesis [85; 86; 23], the exercise also reduces (trend) both body weight and liver weight percentage and WAT weight, whereas it increases the tibialis anterior muscle weight percentage. All these elements correlate with the ability of exercise to increase energy usage (WAT lipids and liver glycogen) as well as muscle weight. Regarding the tibialis anterior muscle, in addition to its increase (weight percentage) with exercise, it decreases with both age (weight percentage) and _Sparc_ KO (weight). It is for these patterns in changes according to genotype, age and exercise that we have chosen the tibialis anterior muscle to measure the expression of COL1A1 and MT-CO1; which allowed us to make a correlation between the genotype-dependent changes in muscle weight and power and the corresponding changes in the expression of these two proteins, depending on SPARC expression. Additionally, the decrease in brain weight percentage with ageing correlates with age-related neurodegeneration and related diseases [87; 88], which are improved by exercise [89; 90; 91] and that, also, correlate with our data, showing an increase (trend) in the brain weight percentage with exercise. Interleukin 6 (among other myokine) is produced by the muscles during exercise [92; 93], which reduces appetite [94] and WAT [93]. This correlates with our results, indicating an effect (trend) of exercise on reducing the body weight and WAT weight percentage, but without any interaction effect on genotype and exercise. This indicates that SPARC absence would not impact the ability of exercise to reduce adiposity. The possibilities could be whether the effect of SPARC is partial since (in _Sparc_ KO mice) the WAT weight is lower in Y mice compare to O mice, or there are other SPARC-independent pathways linking myokine to adiposity reduction, such as IL-6 or also because both WT and _Sparc_ KO mice spent similar amounts of exercise, leading to similar exercise-induced energy expenditure (would have similar impacts of reducing the WAT). For the WAT, both for the age and age \(\times\) genotype (both in WT and _Sparc_ KO mice), we always found an increase in adiposity (weight and weight percentage) with ageing. In addition, there is also a reduction in the muscle mass (percentage) with age and for both WT and _Sparc_ KO mice, which corresponds to the classical ageing profile (decreased muscle mass and increased adiposity) along with increased body weight with ageing [95; 96; 97; 98], as our data show. It is worth noting that, while looking into the effects of genotype \(\times\) age, both for the decrease in SM mass percentage and the increase in WAT weight (as well as weight percentage), we notice that these ageing-induced changes (musculative decrease and adiposity decrease), are more important in O mice than in Y mice. This could be explained by the implication of SPARC in these changes. Indeed, since _SPARC_ expression is downregulated by ageing [8], the consequences of its KO would be more important in Y mice compared to O mice, where its expression is already reduced by ageing.