Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging

Abstract

Aging is accompanied by a progressive loss of skeletal muscle mass and strength. The mechanisms underlying this phenomenon are certainly multifactorial and still remain to be fully elucidated. Changes in the cell nucleus structure and function have been considered among the possible contributing causes. This review offers an overview of the current knowledge on skeletal muscle nuclei in aging, focusing on the impairment of nuclear pathways potentially involved in age-related muscle decline. In skeletal muscle two types of cells are present: fiber cells, constituting the contractile muscle mass and containing hundreds of myonuclei, and the satellite cells, i.e., the myogenic mononuclear stem cells occurring at the periphery of the fibers and responsible for muscle growth and repair. Research conducted on different experimental models and with different methodological approaches demonstrated that both the myonuclei and satellite cell nuclei of aged skeletal muscles undergo several structural and molecular alterations, affecting chromatin organization, gene expression, and transcriptional and post-transcriptional activities. These alterations play a key role in the impairment of muscle fiber homeostasis and regeneration, thus contributing to the age-related decrease in skeletal muscle mass and function.

Keywords: RNA processing; cell nucleus; chromatin; gene expression; myofiber; ribonucleic acid (RNA) transcription; satellite cell; skeletal muscle atrophy.

Figure 1

Transmission electron micrographs of myonuclei of quadriceps muscles from young (a) and old (b) rats. Samples were fixed with paraformaldehyde, embedded in acrylic resin, and stained via ethylenediaminetetraacetic acid (EDTA) method, which reveals RNP-containing nuclear constituents by bleaching the condensed chromatin. In old animals, condensed chromatin (ch) is more abundant, and perichromatin granules (inset) are more numerous than in adult ones, whereas nucleoli (nu) show similar characteristics. Bars: 500 nm; inset: 250 nm [79].

Figure 2

Schematic representation of a skeletal muscle fiber with a myonucleus located just below the sarcolemma. This figure summarizes the age-related alterations in myonuclei described in Section 3.

Figure 3

Transmission electron micrographs of satellite cells of quadriceps muscles from young (a) and old (b) rats. Samples were fixed with paraformaldehyde, embedded in acrylic resin, and stained via EDTA method, which reveals RNP-containing nuclear constituents by bleaching the condensed chromatin. No evident ultrastructural modification of nuclear structural constituents occurs in satellite cell nuclei of young vs. old animals. Condensed chromatin (ch); myofiber (m). Bars: 500 nm.

Figure 4

Schematic representation of a satellite cell located between the myofiber sarcolemma and the basal lamina. This figure summarizes the age-related alterations of satellite cell nuclei described in Section 4.