The Inherent Human Aging Process and the Facilitating Role of Exercise

Arguably the best available depictions of the global physiological changes produced by age are the profiles of world record performance times in swimming, athletics, and cycling, depicting the trajectory of decline in maximal integrated physiological performance capability. The curves suggest that the aging process produces a synchronized, controlled decrease in physiological performance over the human lifespan. The shape of the performance profile by age is essentially independent of discipline, distance, or phenotype. Importantly, the specific times of performance are not the driving force in the production of the shape of the declining performance profile. We suggest that in these highly trained individuals the shape of the curve is generated by the aging process operating on a physiology optimized for any given age. We hypothesize that with adequate training this same profile and trajectory, but with lower performance times, would be generated by all individuals who engage in sufficient physical activity/exercise. Unlike performance, data obtained from examining individual physiological systems or tissues do not give information on the unceasing and changing global integrating functions of the aging process. However, these data do give valuable information about the integrity of physiological systems at a particular age and allow a direct comparison to be made between the effects of inactivity and physical activity/exercise. Being physically active has been shown to have global protective effects on physiological systems and thus facilitates the aging process by maintaining physiological integrity. There is emerging evidence which suggests that physiological regulation of aging may be multi-compartmentalized. We do not advocate exercise as a panacea, but all the evidence indicates that being physically active and exercising is far superior to any other alternative for achieving optimal aging

Aging and skeletal muscle force control: Current perspectives and future directions.

During voluntary muscle contractions, force output is characterized by constant inherent fluctuations, which can be quantified either according to their magnitude or temporal structure, that is, complexity. The presence of such fluctuations when targeting a set force indicates that control of force is not perfectly accurate, which can have significant implications for task performance. Compared to young adults, older adults demonstrate a greater magnitude and lower complexity in force fluctuations, indicative of decreased steadiness, and adaptability of force output, respectively. The nature of this loss-of-force control depends not only on the age of the individual but also on the muscle group performing the task, the intensity and type of contraction and whether the task is performed with additional cognitive load. Importantly, this age-associated loss-of-force control is correlated with decreased performance in a range of activities of daily living and is speculated to be of greater importance for functional capacity than age-associated decreases in maximal strength. Fortunately, there is evidence that acute physical activity interventions can reverse the loss-of-force control in older individuals, though whether this translates to improved functional performance and whether lifelong physical activity can protect against the changes have yet to be established. A number of mechanisms, related to both motor unit properties and the behavior of motor unit populations, have been proposed for the age-associated changes in force fluctuations. It is likely, though, that age-associated changes in force control are related to increased common fluctuations in the discharge times of motor units

Effect of gut microbiome modulation on muscle function and cognition:the PROMOTe randomised controlled trial

Studies suggest that inducing gut microbiota changes may alter both musclephysiology and cognitive behaviour. Gut microbiota may play a role in bothanabolic resistance of older muscle, and cognition. In this placebo controlleddouble blinded randomised controlled trial of 36 twin pairs (72 individuals),aged ≥60, each twin pair are block randomised to receive either placebo orprebiotic daily for 12 weeks. Resistance exercise and branched chain aminoacid (BCAA) supplementation is prescribed to all participants. Outcomes arephysical function and cognition. The trial is carried out remotely using videovisits, online questionnaires and cognitive testing, and posting of equipmentand biological samples. The prebiotic supplement is well tolerated and resultsin a changed gut microbiome [e.g., increased relative Bifidobacterium abundance].There is no significant difference between prebiotic and placebo forthe primary outcome of chair rise time (β=0.579; 95% CI −1.080-2.239p = 0.494). The prebiotic improves cognition (factor score versus placebo(β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate thatcheap and readily available gut microbiome interventions may improve cognitionin our ageing population. We illustrate the feasibility of remotelydelivered trials for older people, which could reduce under-representation ofolder people in clinical trials. ClinicalTrials.gov registration: NCT04309292

PPARα-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia

Hypoxia is a feature of many disease states where convective oxygen delivery is impaired, and is known to suppress oxidative metabolism. Acclimation to hypoxia thus requires metabolic remodelling, however hypoxia tolerance may be aided by dietary nitrate supplementation. Nitrate improves tissue oxygenation and has been shown to modulate skeletal muscle tissue metabolism via transcriptional changes, including through the activation of peroxisome proliferator- activated receptor alpha (PPARα), a master regulator of fat metabolism. Here we investigated whether nitrate supplementation protects skeletal muscle mitochondrial function in hypoxia and whether PPARα is required for this effect. Wild-type and PPARα knockout (PPARα-/-) mice were supplemented with sodium nitrate via the drinking water or sodium chloride as control, and exposed to environmental hypoxia (10% O2) or normoxia for 4 weeks. Hypoxia suppressed mitochondrial respiratory function in mouse soleus, an effect partially alleviated through nitrate supplementation, but occurring independently of PPARα. Specifically, hypoxia resulted in 26% lower mass specific fatty acid-supported LEAK respiration and 23% lower pyruvate-supported oxidative phosphorylation capacity. Hypoxia also resulted in 24% lower citrate synthase activity in mouse soleus, possibly indicating a loss of mitochondrial content. These changes were not seen, however, in hypoxic mice when supplemented with dietary nitrate, indicating a nitrate dependent preservation of mitochondrial function. Moreover, this was observed in both wild-type and PPARα-/- mice. Our results support the notion that nitrate supplementation can aid hypoxia tolerance and indicate that nitrate can exert effects independently of PPARα.This work was supported by King’s College London, the Biotechnology and Biological Sciences Research Councils [grant number: BB/F016581/1] and the Research Councils UK [grant number: EP/E500552/1]

Sera from young and older humans equally sustain proliferation and differentiation of human myoblasts

International audienceUsing a human primary muscle cell culture model the behavior of myoblasts (satellite cells) cultured in human serum obtained from either young or elderly individuals was studied. Serum was obtained from a total of 13 young (7 male and 6 females aged, 23-36 years) and 9 elderly (4 male and 5 females aged 69-84 years) subjects and used in a number of experiments. Myoblasts were extracted from human muscle biopsy samples taken from the vastus lateralis. In the first experiment myoblasts were isolated immediately after extraction from the biopsy in media containing human sera to examine its effects on the onset and progression of Ki67 and desmin expression. No effect of the age of the serum was observed at 3, 5 or 7 days of proliferation. In addition, cells that had been expanded initially in optimum myoblast growth medium (GM, containing foetal calf serum and additional growth factors) prior to culture in medium containing 15% human serum were studied. The proportion of proliferating muscle cells co expressing desmin and Ki67 antigens after 46 hours was again similar in the young and old serum conditions. Culturing these myoblasts in media containing 2% human serum to study their fusion and differentiation also resulted in no difference between young and old serum conditions in terms of the percentage of nuclei inside myosin heavy chain positive myotubes. Despite the variability of different samples of myoblasts, the age of the serum has no affect on the expression of any measured index