In vivo assessment of mitochondrial capacity using NIRS in locomotor muscles of young and elderly males with similar physical activity levels

GeroScience (2020) 42:299–310 https://doi.org/10.1007/s11357-019-00145-4 ORIGINAL ARTICLE In vivo assessment of mitochondrial capacity using NIRS in locomotor muscles of young and elderly males with similar physical activity levels Bart Lagerwaard & Arie G. Nieuwenhuizen Vincent C. J. de Boer & Jaap Keijer & Received: 14 November 2019 / Accepted: 3 December 2019 / Published online: 19 December 2019 # The Author(s) 2019 Abstract Mitochondrial capacity is pivotal to skeletal muscle function and is suggested to decline with age. However, there is large heterogeneity in current data, possibly due to effect modifiers such as physical activity, sex and muscle group. Yet, few studies have compared multiple muscle groups in different age groups with comparable physical activity levels. Here, we newly used near-infrared spectroscopy (NIRS) to characterise mitochondrial capacity in three different locomotor muscles in young (19–25 year) and older (65–71 year), healthy males with similar physical activity levels. Mitochondrial capacity and reperfusion after arterial occlusion was measured in the vastus lateralis (VL), the gastrocnemius (GA) and the tibialis anterior (TA). Physical activity was verified using accelerometry and was not different between the age groups (404.3 ± 214.9 vs 494.9 ± 187.0 activity kcal per day, p = 0.16). Mitochondrial capacity was significantly lower in older males in the GA and VL, but not in the TA (p = 0.048, p = 0.036 and p = 0.64, respectively). Reperfusion rate was not significantly different for the GA (p = 0.55), but was significantly faster in the TA and VL in the young group compared to the older group (p = 0.0094 and p = 0.039, B. Lagerwaard : A. G. Nieuwenhuizen (*) : V. C. J. de Boer : J. Keijer Human and Animal Physiology, Wageningen University and Research, PO Box 338, 6700 AH Wageningen, The Netherlands e-mail: B. Lagerwaard TI Food and Nutrition, PO Box 557, 6700 AN Wageningen, The Netherlands respectively). In conclusion, we identified distinct modes of mitochondrial ageing in different locomotor muscles in a young and older population with similar physical activity patterns. Furthermore, we show that NIRS is suitable for relatively easy application in ageing research and can reveal novel insights into mitochondrial functioning with age. Keywords Near-infrared spectroscopy . Sarcopenia . Reperfusion . Oxidative metabolism Introduction Ageing is associated with a decline in skeletal muscle mass and strength, also known as sarcopenia (Morley et al. 2001). Sarcopenia is thought to be mediated in part by a decline in skeletal muscle mitochondrial capacity, as both the amount of mitochondria and their capacity to generate energy decrease with age in the muscle, resulting in a reduced endurance capacity (Welle et al. 2003; Short et al. 2005; Marzetti et al. 2013). Improving or sustaining muscle mitochondrial capacity could delay the age-related decline in endurance capacity, ultimately retaining physical function and improving quality of life (Lanza et al. 2008; Coen et al. 2013). Due to the pivotal function of mitochondria in the process of ageing, it is essential to routinely and robustly assess mitochondrial capacity. In vivo 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and nearinfrared spectroscopy (NIRS) are existing techniques that can be applied to assess mitochondrial capacity 300 in vivo. Typically, for both techniques, assessment of mitochondrial capacity involves the recovery of muscle homeostasis after exercise; however, 31P-MRS measures the recovery of phosphocreatine (PCr), whereas NIRS measures the recovery of muscle oxygen consumption (mV̇ O2) as a parameter for mitochondrial capacity (Kemp et al. 2015; Grassi and Quaresima 2016). NIRS makes use of the difference in light absorption in the near-infrared region of oxygenated (O2Hb) and deoxygenated haemoglobin and myoglobin (HHb) and can therefore be used to monitor muscle oxygenation. Combining NIRS with arterial occlusions is used to measure mV̇ O 2 in the muscle in vivo (Hamaoka et al. 1996). The mV̇ O2 recovery kinetics after exercise follow a monoexponential function of which the rate constant is used as a measure for mitochondrial capacity, as better-functioning mitochondria will recover mV̇ O2 faster (Motobe et al. 2004). This application of NIRS correlated well to 31P-MRS measurements of PCr recovery and ex vivo high-resolution respirometry (Ryan et al. 2013, 2014b). Although 31PMRS is more widely used, NIRS offers advantages over 31 P-MRS due to its higher mobility, relatively low costs and higher throughput, making NIRS more suitable for routine measurements to, for example, study the effect of age on muscle mitochondrial capacity. Despite its easier applicability, NIRS has not been used to assess the effects of age on muscle mitochondrial capacity in locomotor muscles. Ex vivo respiratory analysis of muscle biopsies taken from the vastus lateralis (VL) show a consistent, negative effect of age on muscle oxidative capacity (Short et al. 2005; Irving et al. 2015; Porter et al. 2015; Lalia et al. 2017). Yet, 31P-MRS analysis of different muscle types report a heterogeneous effect of age on PCr recovery (Fitzgerald et al. 2016). In the VL, most studies showed a negative effect of age on PCr recovery (Conley et al. 2000; Johannsen et al. 2012; Larsen et al. 2012; Choi et al. 2016), but on other locomotor muscles, such as the gastrocnemius muscle (GA) and tibialis anterior (TA), this effect was not observed (Chilibeck et al. 1998; Wray et al. 2009; Larsen et al. 2012; Tevald et al. 2014; Hart et al. 2015). However, some studies do find a negative effect of age on PCr recovery in the GA (McCully et al. 1993; Waters et al. 2003; Layec et al. 2013) and it has been suggested that the conflicting results could arise from the use of different populations with different physical activity levels. Physical activity has a positive effect on muscle GeroScience (2020) 42:299–310 oxidative capacity (Tonkonogi and Sahlin 2002), and is thought to be able to protect from, or at least mitigate, the deteriorating effect of age (Lanza et al. 2008; Larsen et al. 2012). Yet, physical activity is documented to decrease with advancing age (Troiano et al. 2008) and therefore isolating the effect of age on mitochondrial capacity is challenging, as this effect is often entangled with a decrease in physical activity. Therefore, controlling for the confounding effects of physical activity is essential, if not a requisite, in studies looking into the effect of age on mitochondrial capacity. Since it is unclear how mitochondrial capacity is affected in different muscle types with ageing, we aimed to profile mitochondrial capacity using NIRS in three different muscle types, i.e. the GA, TA and VL in young and older healthy males. These muscles serve an important function during locomotion and are accessible by NIRS due to their superficial position. To negate the effect of phys (...truncated)