Sarcopenia refers to a progressive and generalized weakness of skeletal muscle as individuals age. Sarcopenia usually occurs after the age of 60 years and is associated with a persistent decline in muscle strength, function, and quality. A comparison of the risk factors associated with sarcopenia based on the European Working Group on Sarcopenia (1 and 2) in Older People, the Asian Working Group for Sarcopenia (1 and 2), the International Working Group on Sarcopenia, and the Foundation for the National Institutes of Health revealed no consistent patterns. Accordingly, the identification of a single risk factor for sarcopenia is unpredictable due to its “multifactorial” pathogenesis, with the involvement of a multitude of factors. Therefore, the first aim of this review was to outline and propose that the multiple factors associated with sarcopenia need to be considered in combination in the design of new experimentation in this area. A secondary aim was to highlight the biochemical risk factors that are already identified in subjects with sarcopenia to assist scientists in understanding the biology of the pathophysiological mechanisms affecting the old people with sarcopenia. We also briefly discuss primary outcomes (physical) and secondary outcomes (social and financial) of sarcopenia. For future investigative purposes, this comprehensive review may be useful in considering important risk factors in the utilization of a panel of biomarkers emanating from all pathways involved in the pathogenesis of this disease. This may help to establish a uniform consensus for screening and defining this disease. Considering the COVID-19 pandemic, its impact may be exacerbated in older populations, which requires immediate attention. Here, we briefly suggest strategies for advancing the development of smart technologies to deliver exercise in the COVID-19 era in an attempt regress the onset of sarcopenia. These strategies may also have an impact on sarcopenia’s primary and secondary outcomes.

Background: Sarcopenia has been recognized as an inevitable part of aging. However, its severity and the age at which it begins cannot be predicted by age alone. The condition can be categorized into primary or age-related sarcopenia and secondary sarcopenia. Sarcopenia is diagnosed as primary when there are no other specific causes. However, secondary sarcopenia occurs if other factors, including malignancy or organ failure, are evident in addition to aging. The prevalence of secondary sarcopenia is far greater than that of primary sarcopenia and requires special attention. To date, nutrition and exercise have proven to be the best methods to combat this disease. The impact of exercise on subjects suffering from sarcopenia with a specific morbidity is worthy of examination for understanding and prevention. The purpose of this review, therefore, is to summarize recent research that has investigated the impact of exercise in patients with secondary sarcopenia, specifically with one comorbidity. Methods: Pubmed, Web of Science, Embase and Medline databases were searched comprehensively with no date limit for randomized controlled trials. The literature was specifically searched for clinical trials in which subjects were sarcopenic with only one comorbidity participating in an exercise intervention. The most visible comorbidities identified and used in the search were lung disease, kidney disease, heart disease, type 2 diabetes, cancer, neurological diseases, osteoporosis and arthritis. Results: A total of 1752 studies were identified that matched the keywords. After removing duplicates, there were 1317 articles remaining. We extracted 98 articles for full screening. Finally, we included 21 relevant papers that were used in this review. Conclusion: Despite a strong rationale for using exercise to improve muscle mass, quality or physical function in subjects with cancer, type 2 diabetes, kidney disease, lung disease and many more, baseline sarcopenia evaluation has been reported in very few trials. The limited number of studies does not allow us to conclude that exercise can improve sarcopenia in patients with other comorbidities. This review highlights the necessity for wide-ranging research initiatives involving secondary sarcopenic patients.

Cyclooxygenase 2 (COX2) inhibitors have been demonstrated to protect against hypoxia pathogenesis in several investigations. It has also been utilized as an adjuvant therapy in the treatment of COVID-19. COX inhibitors, which have previously been shown to be effective in treating previous viral and malarial infections are strong candidates for improving the COVID-19 therapeutic doctrine. However, another COX inhibitor, ibuprofen, is linked to an increase in the angiotensin-converting enzyme 2 (ACE2), which could increase virus susceptibility. Hence, inhibiting COX2 via therapeutics might not always be protective and we need to investigate the downstream molecules that may be involved in hypoxia environment adaptation. Research has discovered that people who are accustomed to reduced oxygen levels at altitude may be protected against the harmful effects of COVID-19. It is important to highlight that the study’s conclusions only applied to those who regularly lived at high altitudes; they did not apply to those who occasionally moved to higher altitudes but still lived at lower altitudes. COVID-19 appears to be more dangerous to individuals residing at lower altitudes. The downstream molecules in the (COX2) pathway have been shown to adapt in high-altitude dwellers, which may partially explain why these individuals have a lower prevalence of COVID-19 infection. More research is needed, however, to directly address COX2 expression in people living at higher altitudes. It is possible to mimic the gene–environment interaction of higher altitude people by intermittent hypoxia training. COX-2 adaptation resulting from hypoxic exposure at altitude or intermittent hypoxia exercise training (IHT) seems to have an important therapeutic function. Swimming, a type of IHT, was found to lower COX-2 protein production, a pro-inflammatory milieu transcription factor, while increasing the anti-inflammatory microenvironment. Furthermore, Intermittent Hypoxia Preconditioning (IHP) has been demonstrated in numerous clinical investigations to enhance patients’ cardiopulmonary function, raise cardiorespiratory fitness, and increase tissues’ and organs’ tolerance to ischemia. Biochemical activities of IHP have also been reported as a feasible application strategy for IHP for the rehabilitation of COVID-19 patients. In this paper, we aim to highlight some of the most relevant shared genes implicated with COVID-19 pathogenesis and hypoxia. We hypothesize that COVID-19 pathogenesis and hypoxia share a similar mechanism that affects apoptosis, proliferation, the immune system, and metabolism. We also highlight the necessity of studying individuals who live at higher altitudes to emulate their gene–environment interactions and compare the findings with IHT. Finally, we propose COX2 as an upstream target for testing the effectiveness of IHT in preventing or minimizing the effects of COVID-19 and other oxygen-related pathological conditions in the future.