Nuclear Dynamics and Cytoskeletal Coupling Are Altered in Murine Aging Skeletal Muscle
Year: 2018
Type: conference-abstract
Abstract: Skeletal muscle fibers are constantly subjected to mechanical forces, which in turn regulate transcriptional activity in order to maintain muscle structure, and ultimately function. The physical connection between the cytoskeleton and nuclear envelope proteins within the LINC (linker of the nucleus to the cytoskeleton) complex provides the means by which mechanical signals are transmitted to the nucleus. The purpose of this study was to assess changes in nuclear dynamics (mobility, position, and mechanotransduction) and nuclear function in aging skeletal muscle. We tested the hypothesis that altered nuclear dynamics, driven by age-dependent alterations in LINC complex proteins, underscore the transcriptional deficiency in aging that drives sarcopenia. In young (~4 months, N = 3) and aged (~24 months, N = 3) C57BL6 mice, we examined: 1) nuclear velocity and distance traveled in isolated muscle fibers using time-lapse microscopy, 2) LINC (linkers of nucleoskeleton and cytoskeleton) complex protein expression, nesprin-1 nuclear labeling intensity, and nuclear transcriptional activity via histone-H3-acetylation and polyadenylate-binding-nuclear-protein-1, and 3) nuclear strain using a custom-built apparatus to determine alterations in nuclear-cytoskeletal coupling in-vitro during single muscle fiber passive stretch. The findings showed decreased nuclear movement (12.4 ± 0.06 μm vs. 14.7 ± 0.05 μm distance traveled, 0.023 ± 12.5E-5 μm/min vs. 0.027 ± 9.81E-5 μm/min, p<0.05), altered LINC complex expression, and reduced labeling intensity of nesprin-1, in aged compared to young muscle fibers. Aged nuclei in muscle also displayed reduced strain, and altered transcriptional activity. In summary, the results elucidate changes in nuclear-cytoskeletal coupling of aging muscle with consequent changes in nuclear dynamics.
Source: Innovation in Aging
Authors: S Iyer, S Shah, C Ward, J Stains, E Folker, R Lovering
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,977
OpenAlex ID: W2900260748