From Sarcopenia to Frailty: The Pathophysiological Basis and Potential Target Molecules of Intervention

Abstract

Skeletal muscle is not only an endocrine organ but also one of core components of muscloskeletal system. Sarcopenia refers to a decline in the skeletal muscle mass and function. The former involves the size and number of changes in two types of myofibers, lower satellite cell density, and regeneration ability. The latter shows a loss of muscle strength. Frailty is a geriatric syndrome with multisystem impairment associated with increased vulnerability to stressors. Sarcopenia increases the risk of frailty and may be one of the major causes of physical frailty phenotype. Sarcopenia is also potentially associated with cognitive frailty phenotype. Aging might be the common underlying pathophysiology of sarcopenia and frailty. Therefore, there are some potential target molecules in aging-related signaling pathways that might be associated with sarcopenia and frailty. Nevertheless, sarcopenia can mediate metabolism and promote accelerate systemic aging, frailty, and age-related diseases by myokines in an endocrine manner. Lifestyle interventions (resistance exercise and dietary restriction) of gerontoscience are effective in the prevention of sarcopenia. Some pharmacological agents are registered in different phases of clinical trials for sarcopenia intervention. Phytochemicals, mTOR inhibitors, metformin and acarbose, NAD precursors, and sirtuin activators demonstrated that multiple target antiaging effects might also have preventive and therapeutic perspectives on sarcopenia and frailty.

Mediating effect of waist:height ratio on the association between BMI and frailty: the Korean Frailty and Aging Cohort Study

“…Hirani et al (41) also reported that the risk of frailty was significantly higher in the older adults with sarcopenic obesity than in those with non-sarcopenic normal weight, but it was not significantly different from those with non-sarcopenic obesity. It is well known that sarcopenia, defined as an abnormal loss of muscle mass and strength, is one of the major causes for an increase in the risk of frailty (42) . Falsarella et al (43) reported that frail older individuals had a lower muscle mass and higher percentage of body fat compared with non-frail older individuals.…”

Incidence and Predictors of Cognitive Frailty Among Older Adults: A Community-based Longitudinal Study

“…Sarcopenia, characterized by muscle dysfunction, slow gait velocity, and cognitive decline is also known to increase the risk of developing dementia [15]. Sarcopenia is potentially associated with the CF phenotype, as this condition increases the risks of both physical frailty and cognitive impairment [16]. Even though sarcopenia and physical frailty are often used interchangeably, these two phenotypes have different constructs, whereby sarcopenia indicates a progressive decline in the lean body mass or muscle mass that contributes to frailty development [16,17].…”

“…Sarcopenia is potentially associated with the CF phenotype, as this condition increases the risks of both physical frailty and cognitive impairment [16]. Even though sarcopenia and physical frailty are often used interchangeably, these two phenotypes have different constructs, whereby sarcopenia indicates a progressive decline in the lean body mass or muscle mass that contributes to frailty development [16,17]. Hence, the link between physical and cognitive impairments as relevant predictors of dementia warrants the need for a multidimensional approach in the assessments and interventions of older adults with CF.…”

Combined Impact of Positive Screen for Sarcopenia and Frailty on Physical Function, Cognition and Nutrition in the Community Dwelling Older Adult

“… 9 ) Similar to frailty, sarcopenia predisposes older individuals to adverse consequences such as falls, disability, and mortality. 9 , 10 ) The reported prevalence of sarcopenia is 6%–22% in adults aged ≥65 years, depending on the care setting. 11 ) The plausible biological mechanisms linking sarcopenia and frailty include inflammatory responses, oxidative stress, and hormonal dysregulation.…”

“… 11 ) The plausible biological mechanisms linking sarcopenia and frailty include inflammatory responses, oxidative stress, and hormonal dysregulation. 10 , 12 ) The complex intertwining relationship between sarcopenia and frailty has been likened to a “chicken and egg” situation. Sarcopenia is believed to be a fundamental component and possible antecedent of frailty, resulting in reduced muscle strength and gait speed, which characterize the physical manifestation of frailty.…”