Aging and metalloproteinases expression in mussels extracellular matrix

Emerging traits of cachexia in the elderly are usually attributed to disease, reduced physical activity, reduced appetite, reduced metabolic rate, and reduced energy demand. Lower physical activity and malnutrition lead to sarcopenia, understood as age-related skeletal muscle loss, often associated with reductions in strength, speed of contraction, and muscle power. In addition, the loss of muscle mass observed in old age may be due to changes in the nervous and endocrine systems, changes in muscle metabolism, decreased cell proliferation capacity, chronic age-related inflammation and oxidative stress, chronic disease conditions, and use of pharmaceuticals.

Many diseases of muscle are accompanied by increased expression and activity of matrix metalloproteinases (MMP) from the zinc-dependent endopeptidase family, which are involved in the matrix remodeling process that accompanies muscle regeneration. Disorders of collagen accumulation resulting from changes in MMP expression may lead to pathological processes of muscle fibrosis.

With the exception of the membrane-type matrix metalloproteinases (MT-MMP), MMP are synthesized in cells and secreted into the extracellular matrix (ECM). Secretory MMP can aggregate on cell surfaces by binding to MT-MMP, along with molecules responsible for cell adhesion, integrins or proteoglycans. To date, over 20 subtypes of metalloproteinases have been classified, each coded by different genes.

MMP–induced degradation of structural matrix components (such as collagen, laminin, fibronectin) creates space for suitable cells and facilitates cell migration through the matrix. These enzymes are also involved in the regulation of cell activ ity and take part in inflammatory reactions. Many of the peptides released during partial ECM proteolysis may also act as signaling molecules with autocrine or paracrine action. MMPs also participate in cell-cell communication.

Under physiological conditions, MMP are expressed at a very low level in tissues. Induction of expression occurs only in times of ECM reconstruction. Due to their protease activity, these enzymes remain under strict multi-level regulation, i.e. at the level of transcription, post-translational processing, secretion, activation, and degradation. Active MMPs are regulated by tissue inhibitors of metalloproteinases and by numerous cytokines and growth factors.