Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial beta-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.Peer reviewe

Kelan järjestämä kuntoutus vuonna 1987 syntyneille

Tutkimuksessa tarkasteltiin vuonna 1987 Suomessa syntyneiden henkilöiden Kelan järjestämän kuntoutuksen käyttöä. Aineistona oli Kelan kuntoutusratkaisu- ja kuntoutuskustannustiedot Kansallinen syntymäkohortti 1987 -rekisteriaineistoon kuuluville henkilöille vuosilta 1987–2012. Kaikkiaan 6,2 % kohortin henkilöistä oli 25 ikävuoteen mennessä saanut myönteisen ratkaisun jollekin Kelan myöntämälle kuntoutustoimenpiteelle. Eri lakiperustein myönnettyjä kuntoutusratkaisuja tutkittiin omina kokonaisuuksinaan kuntoutustoimenpiteiden, pääsairausdiagnoosien ja kuntoutuksen kustannusten osalta. Myönteisen ratkaisun vaikeavammaisen lääkinnälliselle kuntoutukselle saaneiden henkilöiden määrät olivat pieniä (1,3 % syntymäkohortista) mutta kuntoutustoimenpiteitä eri terapiamuodoissa oli näillä henkilöillä runsaasti, ja myös kuntoutuksen henkilöä kohden lasketut kustannukset olivat korkeimmat. Yleisimmät diagnoosiryhmät olivat älyllinen kehitysvammaisuus ja CP-oireyhtymä. Ammatillista kuntoutusta oli myönnetty 2,3 %:lle kohortista, ja merkittävimmät kuntoutusmuodot henkilömäärittäin olivat ammattikoulutus ja kuntoutustutkimus. Ammatillisen kuntoutuksen kustannuksissa havaittiin selkeää nousua vuoden 2007 jälkeen. Merkittävimmät pääsairausdiagnoosit olivat masennustila ja lievä älyllinen kehitysvammaisuus. Myönteisen kuntoutuspäätöksen oli harkinnanvaraisen kuntoutuksen lakiperusteella saanut 3,2 % kohortista, ja näistä kuntoutustoimenpiteistä yli puolet oli ennen vuoden 2011 alkua myönnettyä kuntoutuspsykoterapiaa. Tämän lisäksi kuntoutus- ja sopeutumisvalmennuskurssit olivat myös merkittävä kuntoutustoimenpide. Masennustila sekä ahdistuneisuushäiriöt olivat merkittävimmät diagnoosiryhmät – myös niillä, joilla kuntoutusmuoto oli jokin muu kuin psykoterapia. Kuntoutuspsykoterapiaa omalla lakiperusteellaan oli saanut 1,3 % henkilöistä, ja psykoterapia olikin fysioterapian jälkeen määrällisesti merkittävin terapiamuoto. Alustavassa alueellisessa tarkastelussa havaittiin huomattavia eroja kuntoutustoimenpiteiden käytössä eri alueilla

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria

Sorting of proteins to vacuoles in plant cells

for correspondence

Experimental <em>Chlamydia pneumoniae</em> infection model: effects of repeated inoculations and treatment

Abstract Chlamydia pneumoniae is a common human pathogen worldwide, which causes both upper and lower respiratory tract infections. In addition, C. pneumoniae infections have been associated with atherosclerosis and other chronic diseases, and successful treatment and eradication of the organism from tissues would therefore be desirable. The purpose of this study was to assess the effects of C. pneumoniae inoculations on the development of chronic infection and atherosclerotic changes in normocholesterolemic, wild-type mice. We also aimed to elucidate the effects of antibiotic and other treatments on the eradication of chlamydia and on the reduction of the pathologic sequelae induced by these infections. Female C57BL/6J mice were fed either normal chow when assessing the effects of acute infection, or a diet supplemented with 0.2% cholesterol when evaluating the atherosclerotic changes. Primary or repeated inoculations with C. pneumoniae isolate K7 were given to the mice intranasally, and the effects of treatments with telithromycin, levofloxacin and erythromycin antimicrobial agents and with the phenolic compounds quercetin, luteolin and octyl gallate were evaluated. The following methods were used to measure infection and treatment effects and the presence of chlamydia in tissue: chlamydia culture, PCR and RT-PCR methods, histology of lung, heart and aortic tissue, serologic methods and measurements of aortic contractility responses. Repeated C. pneumoniae inoculations induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies. Infection was shown to influence aortic endothelial function, and repeated inoculations significantly increased subendothelial lipid accumulation in the aortic sinus area. A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue. All antimicrobial agents eradicated the presence of viable chlamydia effectively; however, PCR positivity persisted in lung tissue despite the treatments. Only immediate treatment after each inoculation was able to decrease aortic sinus lipid accumulation. In conclusion, these data support the role of C. pneumoniae in promoting atherosclerotic development via autoimmune responses and also via direct effects on aortic tissue. Conventional antimicrobial treatments may not effectively eradicate persistent infection, and further studies are warranted to seek for alternative treatment options