The Effects of Aging on the Intramuscular Connective Tissue

Abstract

The intramuscular connective tissue plays a critical role in maintaining the structural integrity of the muscle and in providing mechanical support. The current study investigates age-related changes that may contribute to passive stiffness and functional impairment of skeletal muscles. Variations in the extracellular matrix in human quadriceps femoris muscles in 10 young men, 12 elderly males and 16 elderly females, and in the hindlimb muscles of 6 week old, 8 month old and 2 year old C57BL/6J male mice, were evaluated. Picrosirius red, Alcian blue and Weigert Van Gieson stainings were performed to evaluate collagen, glycosamynoglycans and elastic fibers. Immunohistochemistry analyses were carried out to assess collagen I, collagen III and hyaluronan. The percentage area of collagen was significantly higher with aging (p < 0.01 in humans, p < 0.001 in mice), mainly due to an increase in collagen I, with no differences in collagen III (p > 0.05). The percentage area of elastic fibers in the perimysium was significantly lower (p < 0.01) in elderly men, together with a significant decrease in hyaluronan content both in humans and in mice. No significant differences were detected according to gender. The accumulation of collagen I and the lower levels of hyaluronan and elastic fibers with aging could cause a stiffening of the muscles and a reduction of their adaptability.

Innervation of human superficial fascia

“…The nervous structures in the dense connective tissue of SF can be divided in two groups: thin nerve fiber bundles of 4.8 ± 2.6 µm diameter, and bigger nerve fascicles with a mean diameter of 21.1 ± 12.2 µm. These data are in accord with the values reported in the human hip joint area, in which the SF showed thin nervous structure of 19.1 ± 7.2 µm, with respect to large nerve bundles crossing the muscle with a diameter of 36.4 ± 13.4 µm (Fede et al, 2020). In this work, the only big nerves observed were located in the looser connective tissue areas, constituting passage nerve structures, compared to the small nerve fibers found in majority in the dense tissue.…”

“…This work is the first histological investigation focused on the human SF innervation, which demonstrates that it is hugely innervated, both with autonomic and sensory nerve fibers, according also to our previous work demonstrating that SF of the hip region was the most highly innervated tissue after the skin (skin>Sup Fascia>Deep Fascia>DAT>SAT; Fede et al, 2020). Only some large nerve fascicles cross the superficial fascia to reach the skin, the majority of nerve fibers are located around the vessels, innervating their wall, or are embedded in the fibro-adipose tissue.…”

“…In this study it was not possible to make a quantification and a comparison between the two investigated regions (abdomen and hip), for the low number of collected samples. However, the percentage of S-100 positive area calculated in the abdomen was 0.964% ± 0.110%, showing a bigger innervation with respect to the innervation of the hip area revealed by our group in a precedent article, equal to 0.22% ± 0.06% (Fede et al, 2020). The huge innervation Negative controls.…”

“…Also the presence of a scar in the skin can influence an alteration of the SF: scars are in fact more severe and painful when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. A recent ultrasound imaging study revealed a thickening of the subcutaneous tissue of an injured knee in a young female patient (right/injured= 2.33 mm, left = 1.31 mm) and, in particular, of the SF with hyperechoic thickening of the retinacula cutis, causing significant pain (Pirri et al, 2020). It was demonstrated that the fascial tissue contains specialized sentry fibroblasts, which collectively migrate after injury, progressively causing a contraction of the skin and scar formation (Correa-Gallegos et al, 2019;Jiang et al, 2020).…”

“…Recently, our group (Fede et al, 2020), analyzing the various soft tissues of the human hip region, demonstrated that the superficial fascia was the second most highly innervated tissue (with a mean density of nerves of 33.0 ± 2.5/cm 2 ) after the skin (64.0 ± 5.2/cm 2 ). Also SAT (superficial adipose tissue) and DAT (deep adipose tissue) were less innervated with respect to the fascia, with a mean density of innervation equal to 14.5 ± 1.6/cm 2 and 15.0 ± 6.3/cm 2 , respectively.…”