Sarcopenia: What Is the Origin of This Aging-Induced Disorder?

Abstract

We here review the loss of muscle function and mass (sarcopenia) in the framework of human healthspan and lifespan, and mechanisms involved in aging. The rapidly changing composition of the human population will impact the incidence and the prevalence of aging-induced disorders such as sarcopenia and, henceforth, efforts to narrow the gap between healthspan and lifespan should have top priority. There are substantial knowledge gaps in our understanding of aging. Heritability is estimated to account for only 25% of lifespan length. However, as we push the expected lifespan at birth toward those that we consider long-lived, the genetics of aging may become increasingly important. Linkage studies of genetic polymorphisms to both the susceptibility and aggressiveness of sarcopenia are still missing. Such information is needed to shed light on the large variability in clinical outcomes between individuals and why some respond to interventions while others do not. We here make a case for the concept that sarcopenia has a neurogenic origin and that in manifest sarcopenia, nerve and myofibers enter into a vicious cycle that will escalate the disease progression. We point to gaps in knowledge, for example the crosstalk between the motor axon, terminal Schwann cell, and myofiber in the denervation processes that leads to a loss of motor units and muscle weakness. Further, we argue that the operational definition of sarcopenia should be complemented with dynamic metrics that, along with validated biomarkers, may facilitate early preclinical diagnosis of individuals vulnerable to develop advanced sarcopenia. We argue that preventive measures are likely to be more effective to counter act aging-induced disorders than efforts to treat manifest clinical conditions. To achieve compliance with a prescription of preventive measures that may be life-long, we need to identify reliable predictors to design rational and convincing interventions.

Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines

“…Sarcopenia is caused by a combination of factors, including neurological factors associated with loss of motor neurons, loss of muscle motor units, endocrine changes, and lifestyle changes associated with sedentary behavior and poor nutrition [ 36 , 37 , 38 , 39 ] ( Figure 1 ).…”

“…The mechanisms of development of sarcopenia and SO are diverse, complex, and not fully understood. Several factors can influence the development of sarcopenia in the older adults, including hormone and cytokine imbalance, age-associated systemic inflammation (inflammaging), gut microbiota dysbiosis, microcirculation disorders, metabolic disorders, predominantly obesity and insulin resistance [ 36 , 37 ]. Old age-related physical inactivity and quantitative and qualitative malnutrition will also contribute to this process [ 38 , 39 ].…”

“…All these factors can interact in a complex way on skeletal muscle, reducing the expression of skeletal muscle growth factors and increasing oxidative stress, and the activity of the ubiquitin-proteasome system and autophagy [ 36 ]. These mechanisms disrupt the balance between the synthesis and breakdown of muscle proteins, lead to a decrease in the number and function of satellite cells and dysfunction of mitochondria, and ultimately to atrophy and dysfunction of skeletal muscles [ 36 , 37 , 40 ]. The disorders of the nervous motor system and its interaction with skeletal muscles also play a significant role [ 41 ].…”

Association between CT-Based Preoperative Sarcopenia and Outcomes in Patients That Underwent Liver Resections

“…The aging process often includes sarcopenia, which is characterized by a progressive, generalized loss of skeletal muscle mass and strength [ 3 , 4 ], accompanied by the infiltration of fat and fibrotic connective tissue into muscle [ 5 ]. The latter is the tissue that supports, binds, or distinguishes different types of tissues and organs and is made up of cells and extracellular matrix, which itself is made up of fibers (collagen, reticulin, fibronectin, or elastin) and ground substance [ 6 ]. Sarcopenia also occurs in other conditions, including cancer, reduced caloric intake, poor blood flow to the muscles, mitochondrial dysfunction, and a decline in anabolic hormones [ 7 , 8 , 9 , 10 ].…”

Antioxidant Properties and Cytoprotective Effect of Pistacia lentiscus L. Seed Oil against 7β-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death

“…Several aging mechanisms have been identified, including telomere shortening, genomic instability, epigenetic alterations, and organelle dysfunction (mainly mitochondrial changes), which can trigger cellular senescence [ 18 ]. In addition, among the parameters that can affect the aging of skeletal muscle, oxidative stress is one of the major contributors that can favor skeletal muscle damage [ 19 , 20 ]. Skeletal muscle consumes large quantities of oxygen compared to other tissues, resulting in higher amounts of reactive oxygen species (ROS) [ 21 ].…”