Age-related structural-mechanical property changes in human peroneus longus muscle

Background: Functional impairment of the muscle-tendon unit is one of the most remarkable effects of aging. The function of the peroneus longus muscle is to stabilise the foot and ankle joint. A deterioration of the structural and mechanical properties of this muscle can potentially lead to foot problems in older adults. This study aimed to investigate the effects of age on structural, histological, and mechanical features in peroneus longus muscle samples taken from embalmed cadavers of two different age groups; young adult (30–60 years) and old adult (over 60 years). Materials and methods: The mechanical property was analysed through the results of cross-sectional area, tensile, tensile stress, and modulus of elasticity. The arran- gement of the collagen in the perimysium and tendon was examined by scanning electron microscopy. Fatty infiltration within the musculotendinous junction was evaluated by Masson’ trichrome stained muscle sections.  Results: This study thus provides evidence that there are indeed age-induced mechanical property changes in the peroneus longus muscle, which include reductions in the tensile force, tensile stress, and modulus of elasticity, and is related to the malformation of collagen fibrils and the massive fat accumulation in the musculotendinous junction.  Conclusions: These alterations may further result in a reduction of muscle strength and quality in an older person.

Inheritance of DNA methylation level in healthy human tissues

DNA methylation (DNAm) is the covalent modification of DNA by addition of a methyl group primarily at the cytosine directly upstream of a guanine. DNAm level plays a central role in transcriptional regulation and is linked to disease. Therefore, understanding genetic and environmental influences on DNAm level in healthy tissue is an important step in the elucidation of trait and disease etiology. However, at present only a minority of easy to access human tissues and ethnicities have been investigated. Therefore, we studied DNAm level measured in five human tissues: cerebellum, frontal cortex, pons, temporal cortex and colon in either North American or South American samples. We applied a novel statistical approach to estimate the heritability attributable to genomic regions (regional heritability, ĥ²/r,g ) for DNAm level at thousands of individual DNAm sites genome-wide. In all five tissues, DNAm level was significantly associated with the local genomic region for more DNAm sites than expected by chance. Moreover, DNAm level could be predicted from the local sequence variants with an accuracy that scaled with the estimated ĥ²/r,g . Our results inform on molecular mechanisms regulating DNAm level and trait etiology in several ways. Firstly, DNAm level at DNAm sites located in genomic risk regions and measured in a tissue relevant to the disease can be influenced by the local genetic variants. Specifically, we found that genetic variation within a region associated with Fluid Intelligence was also associated with local DNAm level at the proline-rich coiled-coil 1 (PRRC1) gene in healthy temporal cortex tissue. Additionally, we replicated the finding of a Colorectal Cancer risk variant (rs4925386) associated with two DNAm sites in healthy colon tissue. More generally, we showed that DNAm sites located within a susceptibility region and measured in a relevant tissue exhibit a similar overall pattern of estimated ĥ²/r,g to DNAm sites outwith a susceptibility region. Secondly, the propensity for DNAm level to be associated with the local sequence variation differs with respect to CpG dinucleotide density and genic location. Most notably, DNAm sites located in CpG dense regions of the genome are less likely to be heritable than DNAm sites located in CpG sparse regions of the genome. Additionally, within both CpG dense and CpG sparse regions of the genome intergenic DNAm sites are more likely to be heritable than intragenic DNAm sites. Overall, our study suggests that variation in DNAm level at some DNAm sites is at least partially controlled by nuclear genetic variation. Moreover, DNAm level in healthy tissue has the potential to act as an intermediary in trait variation and etiology