Docosahexaenoic Acid, a Potential Treatment for Sarcopenia, Modulates the Ubiquitin–Proteasome and the Autophagy–Lysosome Systems

Abstract

One of the characteristic features of aging is the progressive loss of muscle mass, a nosological syndrome called sarcopenia. It is also a pathologic risk factor for many clinically adverse outcomes in older adults. Therefore, delaying the loss of muscle mass, through either boosting muscle protein synthesis or slowing down muscle protein degradation using nutritional supplements could be a compelling strategy to address the needs of the world’s aging population. Here, we review the recently identified properties of docosahexaenoic acid (DHA). It was shown to delay muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins. Both the ubiquitin–proteasome and the autophagy–lysosome systems are modulated by DHA. Collectively, growing evidence indicates that DHA is a potent pharmacological agent that could improve muscle homeostasis. Better understanding of cellular proteolytic systems associated with sarcopenia will allow us to identify novel therapeutic interventions, such as omega-3 polyunsaturated fatty acids, to treat this disease.

Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update

“…These findings support omega-3 polyunsaturated fatty acid administration as a potential therapeutic tool to reduce muscle loss and inflammation linked to accumulated fatty acids in secondary sarcopenia. Likewise, DHA has also recently been found to modulate the ubiquitin–proteasome and the autophagy–lysosome systems, potentially improving muscle integrity and function by decreasing proteolysis and inflammation for sarcopenia [ 40 ].…”

Comparison of SARC-F Score among Gastrointestinal Diseases

“…Nutritional aspects and inflammatory aspects are both relevant for the incidence of sarcopenia [29]. Systemic inflammation, as reflected by CRP level, can activate ubiquitin-proteasome pathways, leading to muscle proteolysis [30]. Inflammatory cytokines such as IL-6 and TNFα can also cause insulin resistance, apoptosis, and dysfunction of mitochondria, which are involved in energy production, excessive production of reactive oxygen species, and the acceleration of muscle protein breakdown to eventually result in sarcopenia [31][32][33][34][35][36][37].…”

Cancer-Associated Muscle Wasting—Candidate Mechanisms and Molecular Pathways

“…Docosahexaenoic acid (DHA) modulates the ubiquitin-proteasome and the autophagy-lysosome systems. DHA can delay muscle wasting by stimulating oxidative stress and inhibiting proteasomal degradation of muscle proteins [151]. Novel therapeutics can also be considered.…”