Sarcopenia – a progressive disorder characterized by skeletal muscle loss and functional decline, is influenced by both genetic and environmental factors.¹Sarcopenia is a multifactorial disorder that occurs due to the aging process and is exacerbated by conditions like obesity, diabetes, and cardiovascular diseases.

The pathophysiology of sarcopenia is closely linked to a reduction in motoneurons that innervate muscle fibers, which leads to impaired coordination of contractile proteins, mitochondria, and the sarcoplasmic reticulum. This imbalance disrupts muscle homeostasis, precipitating a decline in muscle strength and physical performance. A notable hallmark of sarcopenia is the selective atrophy of type II muscle fibers, which is compounded by increased fat infiltration and decreased satellite cell activity, both of which are essential for muscle regeneration.

Adipose tissue also contributes to muscle degradation, especially in individuals with obesity or metabolic syndrome. Changes in adipocyte secretory patterns cause increased production of pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and plasminogen activator inhibitor-1 (PAI-1), while reducing anti-inflammatory molecules like IL-10. This inflammatory cascade contributes to muscle degradation, oxidative stress, and mitochondrial dysfunction. The accumulation of reactive oxygen and nitrogen species (ROS/RNS) further exacerbates cellular damage, leading to impaired mitochondrial function, decreased antioxidant response, and increased apoptotic signaling, all of which accelerate muscle loss.

Additionally, sarcopenia is associated with systemic inflammation, particularly in chronic diseases like peripheral arterial disease (PAD), heart failure (HF), and chronic obstructive pulmonary disease (COPD). These conditions induce metabolic stress, impair protein synthesis, and promote excessive oxidative damage, leading to muscle deterioration. Inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha(TNF-α) contribute to increased muscle catabolism and apoptosis, further linking sarcopenia to multimorbidity.

Owing to its complex pathophysiology, sarcopenia management necessitates a multifaceted approach. Treatment strategies must incorporate lifestyle interventions, nutritional support, and pharmacological therapies to mitigate sarcopenia's impact and improve patient outcomes.²

Sources:

1.      Aslam MA, Ma EB, Huh JY. Pathophysiology of sarcopenia: Genetic factors and their interplay with environmental factors. Metabolism. 2023 Dec 1;149:155711.

2.      Mellen RH, Girotto OS, Marques EB, Laurindo LF, Grippa PC, Mendes CG, Garcia LN, Bechara MD, Barbalho SM, Sinatora RV, Haber JF. Insights into pathogenesis, nutritional and drug approach in sarcopenia: a systematic review. Biomedicines. 2023 Jan 5;11(1):136.