Aging influences cellular and molecular responses of apoptosis to skeletal muscle unloading

The influence of aging on skeletal myocyte apoptosis is not well understood. In this study we examined apoptosis and apoptotic regulatory factor responses to muscle atrophy induced via limb unloading following loading-induced hypertrophy. Muscle hypertrophy was induced by attaching a weight to one wing of young and aged Japanese quails for 14 days. Removing the weight for 7 or 14 days after the initial 14 days of loading induced muscle atrophy. The contralateral wing served as the intra-animal control. A time-released bromodeoxyuridine (BrdU) pellet was implanted subcutaneously with wing weighting to identify activated satellite cells/muscle precursor cells throughout the experimental period. Bcl-2 mRNA and protein levels decreased after 7 days of unloading, but they were unchanged after 14 days of unloading in young muscles. Bcl-2 protein level but not mRNA level decreased after 7 days of unloading in muscles of aged birds. Seven days of unloading increased the mRNA level of Bax in muscles from both young and aged birds. Fourteen days of unloading increased mRNA and protein levels of Bcl-2, decreased protein levels of Bax, and decreased nuclear apoptosis-inducing factor (AIF) protein level in muscles of aged birds. BrdU-positive nuclei were found in all unloaded muscles from both age groups, but the number of BrdU-positive nuclei relative to the total nuclei decreased after 14 days of unloading compared with 7 days of unloading. The TdT-mediated dUTP nick end labeling (TUNEL) index was higher after 7 days of unloading in both young and aged muscles and after 14 days of unloading in aged muscles. Immunofluorescent staining revealed that almost all of the TUNEL-positive nuclei were also BrdU immunopositive, suggesting that activated satellite cell nuclei (both fused and nonfused) underwent nuclear apoptosis during unloading. There were significant correlations among levels of Bcl-2, Bax, and AIF and TUNEL index. Our data are consistent with the hypothesis that apoptosis regulates, at least in part, unloading-induced muscle atrophy and loss of activated satellite cell nuclei in previously loaded muscles. Moreover, these data suggest that aging influences the apoptotic responses to prolonged unloading following hypertrophy in skeletal myocytes. satellite cells; Bcl-2 protein family     

A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages

SIR2 genes control life span in model organisms, playing a central role in evolutionarily conserved pathways of aging and longevity. We wanted to verify whether similar effects may act in humans too. First, we searched for variability in the human sirtuin 3 gene (SIRT3) and discovered a VNTR polymorphism (72-bp repeat core) in intron 5. The alleles differed both for the number of repeats and for presence/absence of potential regulatory sites. Second, by transient transfection experiments, we demonstrated that the VNTR region has an allele-specific enhancer activity. Third, by analyzing allele frequencies as a function of age in a sample of 945 individuals (20-106 years), we found that the allele completely lacking enhancer activity is virtually absent in males older than 90 years. Thus the underexpression of a human sirtuin gene seems to be detrimental for longevity as it occurs in model organisms.     

Do anthropogenic matrix and life-history traits structure small mammal populations? A meta-analytical approach

Conservation Genetics - Understanding the genetic responses of different species to the landscape attributes is essential to improve conservation actions and decision-making. However, making...     

Ectomycorrhizal communities in a productive Tuber aestivum Vittad. orchard: composition, host influence and species replacement

Truffles (Tuber spp.) and other ectomycorrhizal species form species-rich assemblages in the wild as well as in cultivated ecosystems. We aimed to investigate the ectomycorrhizal communities of hazels and hornbeams that are growing in a 24-year-old Tuber aestivum orchard. We demonstrated that the ectomycorrhizal communities included numerous species and were phylogenetically diverse. Twenty-nine ectomycorrhizal taxa were identified. Tuber aestivum ectomycorrhizae were abundant (9.3%), only those of Tricholoma scalpturatum were more so (21.4%), and were detected in both plant symbionts with a variation in distribution and abundance between the two different hosts. The Thelephoraceae family was the most diverse, being represented by 12 taxa. The overall observed diversity represented 85% of the potential one as determined by a jackknife estimation of richness and was significantly higher in hazel than in hornbeam. The ectomycorrhizal communities of hornbeam trees were closely related phylogenetically, whereas no clear distribution pattern was observed for the communities in hazel. Uniform site characteristics indicated that ectomycorrhizal relationships were host mediated, but not host specific. Despite the fact that different plant species hosted diverse ectomycorrhizal communities and that the abundance of T. aestivum differed among sites, no difference was detected in the production of fruiting bodies.     

Bioinformatics for personal genome interpretation

An international consortium released the first draft sequence of the human genome 10 years ago. Although the analysis of this data has suggested the genetic underpinnings of many diseases, we have not yet been able to fully quantify the relationship between genotype and phenotype. Thus, a major current effort of the scientific community focuses on evaluating individual predispositions to specific phenotypic traits given their genetic backgrounds. Many resources aim to identify and annotate the specific genes responsible for the observed phenotypes. Some of these use intra-species genetic variability as a means for better understanding this relationship. In addition, several online resources are now dedicated to collecting single nucleotide variants and other types of variants, and annotating their functional effects and associations with phenotypic traits. This information has enabled researchers to develop bioinformatics tools to analyze the rapidly increasing amount of newly extracted variation data and to predict the effect of uncharacterized variants. In this work, we review the most important developments in the field--the databases and bioinformatics tools that will be of utmost importance in our concerted effort to interpret the human variome.     

Interleukin-15 and interleukin-15R alpha SNPs and associations with muscle, bone, and predictors of the metabolic syndrome

The aims of this study were to examine associations between two SNPs in the human IL-15 gene and three SNPs in the IL-15Ralpha gene with predictors of metabolic syndrome and phenotypes in muscle, strength, and bone at baseline and in response to resistance training (RT). Subjects were Caucasians who had not performed RT in the previous year and consisted of a strength cohort (n=748), volumetric cohort (n=722), and serum cohort (n=544). Subjects completed 12 weeks of unilateral RT of the non-dominant arm, using their dominant arm as an untrained control. ANCOVA analyses revealed gender-specific associations with: (1) IL-15 SNP (rs1589241) and cholesterol (p=0.04), LDL (p=0.02), the homeostasis model assessment (HOMA; p=0.03), and BMI (p=0.002); (2) IL-15 SNP (rs1057972) and the pre- to post-training absolute difference in 1RM strength (p=0.02), BMI (p=0.008), and fasting glucose (p=0.03); (3) IL-15Ralpha SNP (rs2296135) and baseline total bone volume (p=0.04) and the pre- to post-training absolute difference in isometric strength (p=0.01); and 4) IL-15Ralpha SNP (rs2228059) and serum triglycerides (p=0.04), baseline whole muscle volume (p=0.04), baseline cortical bone volume (p=0.04), and baseline muscle quality (p=0.04). All associations were consistent in showing a potential involvement of the IL-15 pathway with muscle and bone phenotypes and predictors of metabolic syndrome.