Impact of reduced physical activity on human health: comparison of younger and older adults

Physical inactivity (PI) is an independent risk factor for overall health. As it is very widespread (> 10 hours daily), it is a 2nd mortality risk factor and since 2019 WHO guidelines restrict sedentary behaviour. In addition, PI can be considered pandemic as it decreases exercise tolerance and dramatically increases disease risk. Although PI affects overall health, the main deterioration occurs at the level of loss of muscle size and function, impaired central and peripheral motor control, and impaired oxidative metabolism and insulin resistance. Most previous studies have focused only on young, and few on old. There is growing interest in experimental studies of physical activity restriction to investigate the pathophysiological mechanisms by which PI affects human health. Most previous studies examining these aspects were conducted in laboratory settings using extreme models of unloading (e.g., bed rest). More recently, an additional systemic model of reduced PI has been proposed, termed step reduction (SR). SR consists of suddenly reducing participants' habitual daily steps to a lower daily step count, ranging from ∼750 to ∼4500 steps/day. Compared with bed rest, SR is considered a milder form of PI because participants continue to be exposed to exercise stimuli. However, this model appears to be much closer to real-world conditions, more ecologically valid, and capable of mimicking the detrimental effects of a sedentary lifestyle. In addition, it should be noted that prolonged bed rest is less common than periods of lower physical activity and that a low number of daily steps is strongly associated with an increased risk of mortality. Project will focus on comparing neuromuscular, cardiovascular, metabolic, and cognitive deterioration after 21-day SR between young and old of both sexes. Loss of muscle mass at SR is a consistent finding in both young and old, with a decrease in muscle protein synthesis considered the major mechanisms for loss of muscle mass. The effects of SR on muscle function and physical performance are more controversial. In older, a decrease in maximal isometric strength of knee extensors has been found in some but not all SR studies, and the explanation for this is still lacking. Our study will investigate whether these changes in neuromuscular integrity and function can also be detected using a SR model to unravel their potential association with impairments in muscle strength and physical performance. Therefore, we will conduct two 21-day SR (with 21-day recovery period) in 15 healthy younger men + 15 women (18-30 years) and 15 healthy older men + 15 women (65+ years) to gain insights into pronounced SR-induced loss of muscle volume, strength and power. Accordingly, we will examine the morphology, integrity, and function of the neuromuscular system before and after SR and after 21-day supervised recovery. All participants will firstly reduce step count from ~8,000-15,000 to ~3,500 and secondly to ~1,500 daily steps during the 21-day SR). We hypothesize that: (i) old will deteriorate more than young; (ii) old will recover less than young when only the original lifestyle is restored; (iii) an analysis of interindividual variability (covariates: Gender, Age, Diet, Daily steps during SR and recovery, Previous physical activity, Original fitness) will identify the groups of participants with the highest/least deterioration/recovery and the minimum daily step count to avoid deterioration. In addition, we will test the hypotheses that: (i) neuromuscular junction instability will occur in both groups after 21-day SR more in the old than in the young and more at 1,500 than at 3,500 daily steps; (ii) impaired neuromuscular transmission could be associated with changes in calcium signalling within fibres; (iii) and such changes could be associated with impairments in activation capacity.