Feed aggregator

Abstract  It is known that a global decrease in food ingestion (dietary restriction, DR) lowers mitochondrial ROS generation (mitROS) and oxidative stress in young immature rats. This seems to be caused by the decreased methionine ingestion of DR animals. This is interesting since isocaloric methionine restriction in the diet (MetR) also increases, like DR, rodent maximum longevity. However, it is not known if old rats maintain the capacity to lower mitROS generation and oxidative stress in response to MetR similarly to young immature animals, and whether MetR implemented at old age can reverse aging-related variations in oxidative stress. In this investigation the effects of aging and 7 weeks of MetR were investigated in liver mitochondria of Wistar rats. MetR implemented at old age decreased mitROS generation, percent free radical leak at the respiratory chain and mtDNA oxidative damage without changing oxygen consumption. Protein oxidation, lipoxidation and glycoxidation increased with age, and MetR in old rats partially or totally reversed these age-related increases. Aging increased the amount of SIRT1, and MetR decreased SIRT1 and TFAM and increased complex IV. No changes were observed in the protein amounts of PGC1, Nrf2, MnSOD, AIF, complexes I, II and III, and in the extent of genomic DNA methylation. In conclusion, treating old rats with isocaloric short-term MetR lowers mitROS production and free radical leak and oxidative damage to mtDNA, and reverses aging-related increases in protein modification. Aged rats maintain the capacity to lower mitochondrial ROS generation and oxidative stress in response to a short-term exposure to restriction of a single dietary substance: methionine.

• Content Type Journal Article
• Category Research Article
• Pages 1-13
• DOI 10.1007/s10522-012-9384-5
• Authors
  • Inés Sanchez-Roman, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Alexia Gómez, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Irene Pérez, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Carlota Sanchez, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Henar Suarez, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Alba Naudí, Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
  • Mariona Jové, Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
  • Mónica Lopez-Torres, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain
  • Reinald Pamplona, Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
  • Gustavo Barja, Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Aging can be described as the accumulation of changes in organisms over time. Aging in organisms undergoing caloric restriction (CR) is widely considered as a slowed version of aging under ad libitum (AL) conditions. However, here we argue that aging under optimized CR is fundamentally different from aging under AL based on the following facts: (1) Comparing the two dietary groups, several age-related changes run in the opposite direction over time; (2) Switching from an AL to a CR diet clearly reverts (not only delays) several “normal” accumulated changes; (3) major causes of death are as different between both groups as they are between species. These observations support the idea that CR and AL initially modulate different metabolic and physiological programs, which exclusively over time generate two biologically different organisms. Such distinct diet-related senescence is analogous to the divergent aging processes and causes of death observed between castes of social insects, such as queens versus workers (“caste-related-senescence”) and also between breeding versus non-breeding semelparous animals (“reproduction-related-senescence”). All these aging phenotypes are different not because they accumulate changes at a different rate, but because they accumulate different changes over time. Thus, the environment does not simply affect the individual aging rate through stochastic effects (e.g. U.V.) but also modulates the activation of a particular program/strategy that influences lifespan (e.g. caste, calorie intake). We refer to the environment-dependent aging patterns encoded by the genome as “senemorphism”. Based on this idea we propose experimental schemes for aging, evolution and biomedical research.

• Content Type Journal Article
• Category Opinion
• Pages 1-10
• DOI 10.1007/s10522-012-9383-6
• Authors
  • Lucas Siqueira Trindade, Heddle Initiative Research Unit, Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
  • Alex Balduino, Development & Technology Research Center, Universidade Veiga de Almeida, Rio de Janeiro, RJ 20271-020, Brazil
  • Toshiro Aigaki, Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Hachioji, Tokyo, 192-0397 Japan
  • Jonathan G. Heddle, Heddle Initiative Research Unit, Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Aged skeletal muscle displays increased fibrosis and impaired regeneration. While it is not well characterized how skeletal muscle fibroblasts contribute to these phenomena, transforming growth factor-β1 (TGF-β1) and Delta/Notch signaling have been implicated to influence muscle regeneration. In this study, a unique combination of aging phenotypes is identified in differentiating fibroblasts (myofibroblasts), proliferating fibroblasts, and muscle precursor cells (MPCs) that characterize an impaired regenerative potential observed in aged skeletal muscle. Using a novel dual-isolation technique, that isolates fibroblasts and MPCs from the same rat skeletal muscle sample, and cell culture conditions of 5 % O2 and 5 % CO2, we report for the first time that myofibroblasts from 32-mo-old skeletal muscle, compared to 3-mo-old, display increased levels of mRNA for the essential extracellular matrix (ECM) genes, collagen 4α1 (83 % increase), collagen 4α2 (98 % increase), and laminin 2 (113 % increase), as well as increased levels of mRNA for the inflammatory markers, interleukin-6 (4.3-fold increase) and tumor necrosis factor α (3.2-fold increase), and TGF-β1 (84 % increase), whose protein controls proliferation and differentiation. Additionally, we demonstrate that proliferating fibroblasts from 32-mo-old skeletal muscle display increased levels of mRNA for the Notch ligand, Delta 1 (≥2.0-fold increase). Together, these findings suggest that increased expression of ECM and inflammatory genes in myofibroblasts from 32-mo-old skeletal muscle may contribute to the fibrogenic phenotype that impairs regeneration in aged skeletal muscle. Furthermore, we believe the novel dual-isolation technique developed here may be useful in studies that investigate communications among MPCs, fibroblasts, and myofibroblasts in skeletal muscle.

• Content Type Journal Article
• Category Research Article
• Pages 1-16
• DOI 10.1007/s10522-012-9382-7
• Authors
  • Kevin A. Zwetsloot, Department of Health, Leisure, and Exercise Science, Appalachian State University, 111 Rivers Street, ASU Box 32071, Boone, NC 28608, USA
  • Anders Nedergaard, Centre for Healthy Aging, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark
  • Leigh T. Gilpin, Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA
  • Thomas E. Childs, Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA
  • Frank W. Booth, Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Age related mitochondrial impairments are considered to be contributors of cardiovascular disease. This study was designed to examine whether early life exposure to lead (Pb) would lead to the Pb induced age related hematological and cardiac mitochondrial changes in rats, and to further examine the protective effect of nutrient metal mixture containing zinc, iron and calcium. Male albino rats were lactationally exposed to 0.2 % Pb-acetate or 0.2 % Pb-acetate together nutrient metal mixture (0.02 %) in drinking water of the mother from postnatal day 1 (PND1) to PND 21. The hemoglobin level, the activities of serum ceruloplasmin oxidase, cardiac mitochondrial enzymes catalase, manganese superoxide dismutase, copper zinc superoxide dismutase, glutathione peroxidase, succinate dehydrogenase, lipid peroxidation and Pb levels were analyzed at PND 45, 12 and 24 months age. The hematological parameters, and the cardiac TCA cycle and antioxidant enzyme markers and lipid peroxidation levels were significantly altered following Pb exposure in young rats (PND 45). These Pb induced changes persisted, though at much lower level in the aged rats. The Pb levels in blood and heart were also significantly higher in PND 45 and remained at detectable levels in older rats. The nutrient metal mixture containing iron, calcium and zinc significantly reversed these changes in all the chosen markers except lipid peroxidation in which the reversal effect was not significant. These data are supportive of age-related cardiac mitochondrial impairments and further provide evidence for the protective efficacy of nutrient metal mixture against Pb-toxicity.

• Content Type Journal Article
• Category Research Article
• Pages 1-10
• DOI 10.1007/s10522-012-9380-9
• Authors
  • D. Chand Basha, Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517 502, India
  • S. Sadak Basha, Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517 502, India
  • G. Rajarami Reddy, Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517 502, India

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  The impact of aging on joints can have a profound effect on an individual’s functioning. Our objectives were to assess the histological and mechanical properties of the knee joint capsule and articular cartilage with aging, and to examine the effects of exercise on age-related changes in the knee joint. 2-year-old Wistar rats were divided into a sedentary control group and an exercise-trained group. 10-week-old animals were used to investigate the changes with aging. The joint capsule and cartilage were evaluated with histological, histomorphometric, immunohistochemical, and mechanical analyses. Severe degenerative changes in articular cartilage were observed with aging, whereas exercise apparently did not have a significant effect. The articular cartilage of aged rats was characterized by damage to the cartilage surface, cell clustering, and an abnormal cartilage matrix. Histomorphometric analysis further revealed changes in cartilage thickness as well as a decreased number of chondrocytes. Aging led to stiffness of the articular cartilage and reduced the ability to dissipate the load and distribute the strain generated within the joint. Joint stiffness with aging was independent of capsular stiffness and synovitis was not a characteristic feature of the aging joint. This study confirms that aging alone eventually leads to joint degeneration in a rat model. The lack of recovery in aging joint changes may be due to several factors, such as the duration of the intervention and the regeneration ability of the cartilage.

• Content Type Journal Article
• Category Research Article
• Pages 1-13
• DOI 10.1007/s10522-012-9381-8
• Authors
  • Hideki Moriyama, Graduate School of Health Sciences, Hiroshima University, Hiroshima, 734-8551 Japan
  • Naohiko Kanemura, School of Health and Social Services, Saitama Prefectural University, Saitama, 343-8540 Japan
  • Inge Brouns, Laboratory of Cell Biology and Histology, University of Antwerp, 2020 Antwerp, Belgium
  • Isabel Pintelon, Laboratory of Cell Biology and Histology, University of Antwerp, 2020 Antwerp, Belgium
  • Dirk Adriaensen, Laboratory of Cell Biology and Histology, University of Antwerp, 2020 Antwerp, Belgium
  • Jean-Pierre Timmermans, Laboratory of Cell Biology and Histology, University of Antwerp, 2020 Antwerp, Belgium
  • Junya Ozawa, Department of Physical Therapy, Hiroshima International University, Hiroshima, 739-2695 Japan
  • Nobuhiro Kito, Department of Physical Therapy, Hiroshima International University, Hiroshima, 739-2695 Japan
  • Toshiaki Gomi, School of Health and Social Services, Saitama Prefectural University, Saitama, 343-8540 Japan
  • Masataka Deie, Graduate School of Health Sciences, Hiroshima University, Hiroshima, 734-8551 Japan

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Methods for quantitative oral administration of various substances to Caenorhabditis elegans are needed. Previously, we succeeded in oral administration of hydrophilic substances using liposomes. However, an adequate system for delivery of hydrophobic chemicals was not available. In this study, we developed a method for oral administration of lipid-soluble substances to C. elegans. γ-cyclodextrin (γCD), which delivers hydrophobic chemicals, was used to make micro-particles of inclusion compounds that can be ingested by bacteriophagous nematodes, which do not distinguish these micro-particles from their food bacteria. Successful oral delivery of the hydrophobic fluorescent reagent 3,3′-dioctadecyloxacarbocyanine perchlorate into the intestines of C. elegans was observed. Oral administration of the hydrophobic antioxidants tocotrienol, astaxanthin, or γ-tocopherol, prolonged the nematode lifespan; tocotrienol rendered them resistant to infection with the opportunistic pathogen Legionella pneumophila. In contrast, older conventional delivery methods that involve incorporation of chemicals into the nematode growth medium or pouring chemicals onto the plate produced weaker fluorescence and no longevity effects. Our method efficiently and quantitatively delivers hydrophobic solutes to nematodes, and a minimum effective dose was estimated. In combination with our liposome method, this γCD method expands the usefulness of C. elegans for the discovery of functional food factors and for screening drug candidates.

• Content Type Journal Article
• Category Method
• Pages 1-8
• DOI 10.1007/s10522-012-9378-3
• Authors
  • Noriko Kashima, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan
  • Yukiko Fujikura, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan
  • Tomomi Komura, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan
  • Shogo Fujiwara, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan
  • Miyuki Sakamoto, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan
  • Keiji Terao, CycloChem Co., Ltd., KIBC 654R, 5-5-2, Kobe, 650-0047 Japan
  • Yoshikazu Nishikawa, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585 Japan

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Protein arginine methyltransferases (PRMTs) generate asymmetric and symmetric dimethyl-arginines by catalyzing the transfer of methyl groups from s-adenosyl-l-methionine to arginines in target proteins. Previously, we observed that the expression and activity of PRMTs were significantly down-regulated in replicatively senescent fibroblasts compared to young fibroblasts. In this study, we determined the level of three PRMT family members (PRMT1, PRMT4, and PRMT5) and the arginine methylation status in eight tissues from 6- and 24-month-old rats. We observed tissue-specific down-regulation of individual PRMT members in testis, thymus, kidney, lung, and heart from 24-month-old as compared to 6-month-old rats. Specifically, we observed reduced levels of PRMT1 in thymus and lung, reduced levels of PRMT4 in testis, thymus, and hearts, and reduced levels of PRMT5 in all five tissues. PRMT enzyme activity on histones generally correlated with PRMT expression. Furthermore, we observed a reduction in asymmetric and symmetric dimethylation on proteins in aged thymus and lung, and a reduction in symmetric dimethylation in aged testes relative to the testes harvested from young rats. These results suggest that individual PRMT proteins have tissue-specific functions and are regulated in a tissue-specific and age-dependent manner.

• Content Type Journal Article
• Category Research Article
• Pages 1-8
• DOI 10.1007/s10522-012-9379-2
• Authors
  • Eunyoung Hong, Department of Preventive Medicine & Medical Research Center for Environmental Toxico-Genomics and Proteomics, Korea University Medical College, 5-Ka, Anam-dong, Sungbuk-Ku, Seoul, 136-705 Korea
  • Yongchul Lim, Department of Preventive Medicine & Medical Research Center for Environmental Toxico-Genomics and Proteomics, Korea University Medical College, 5-Ka, Anam-dong, Sungbuk-Ku, Seoul, 136-705 Korea
  • Eunil Lee, Department of Preventive Medicine & Medical Research Center for Environmental Toxico-Genomics and Proteomics, Korea University Medical College, 5-Ka, Anam-dong, Sungbuk-Ku, Seoul, 136-705 Korea
  • Minyoung Oh, Department of Preventive Medicine & Medical Research Center for Environmental Toxico-Genomics and Proteomics, Korea University Medical College, 5-Ka, Anam-dong, Sungbuk-Ku, Seoul, 136-705 Korea
  • Daeho Kwon, Department of Microbiology, College of Medicine, Kwandong University, 522 Naegok-dong, Gangneung-si, Kwangwon-do 210-701, Korea

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Calorie restriction (CR) is by far the most robust intervention, genetic or environmental, for slowing down ageing in mammals. The identification of sirtuins as NAD-dependent protein deacetylases led to the proposal that they mediate the health benefits of CR (Guarente, 2000).

Abstract  Mild stresses may have positive effects on aging, longevity and resistance to severe stresses at various ages in Drosophila melanogaster. However, no study has combined two mild stresses to know whether more positive effects would be observed than with each stress alone. Cold and hypergravity (HG) have positive effects on some traits, but negative ones can also be observed, particularly in females. This study combined in the same flies cold and HG exposure. When cold and HG had each positive or negative effects their combination had additive effects but, when only one of the pretreatments had some effect, the effect of their combination usually reflected this effect. Therefore, combining two mild stresses with positive effects on aging and longevity can be more efficient than each stress alone. However, if one of these mild stresses had negative effects and the other one positive effects, the net result of their combination could be the suppression of the positive effect of the second stress. On the whole, if the net result of the combination of two mild stresses would be negative, it would be preferable not to combine them.

• Content Type Journal Article
• Category Research Article
• Pages 1-16
• DOI 10.1007/s10522-012-9377-4
• Authors
  • Éric Le Bourg, Centre de Recherche sur la Cognition Animale, Université Paul-Sabatier, UMR CNRS 5169, 118 route de Narbonne, 31062, Toulouse Cedex 9, France

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Editorial: a systematic end to “muddling through”?

• Content Type Journal Article
• Pages 1-2
• DOI 10.1007/s10522-012-9376-5
• Authors
  • Richard Faragher, School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Brighton, BN2 4GJ UK
  • Elizabeth Ostler, School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Brighton, BN2 4GJ UK

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729
• Journal Volume Volume 13
• Journal Issue Volume 13, Number 1

Abstract  The free radical theory of aging says that increased oxidative stress and mitochondrial dysfunction are associated with old age. In the present study we have investigated the effects of cellular senescence on muscle energetic by comparing mitochondrial content and function in cultured muscle satellite cells at early and late passage numbers. We show that cultured muscle satellite cells undergoing senescence express a reduced mitochondrial mass, decreased whole cell ATP level, normal to increased mitochondrial ATP production under ATP utilization, increased mitochondrial membrane potential and increased superoxide/mitochondrial mass and hydrogen peroxide/mitochondrial mass ratios. Moreover, the increased ROS production correlates with the corresponding mitochondrial ATP production. Thus, myotubes differentiated from human myoblasts undergoing senescence have a reduced mitochondrial content, but the existent mitochondria express normal to increased functional capabilities. The present data suggest that the origin of aging lies outside the mitochondria and that a malfunction in the cell might be preceding and initiating the increase of mitochondrial ATP synthesis and concomitant ROS production in the single mitochondrion in response to decreased mitochondrial mass and reduced extra-mitochondrial energy supply. This then can lead to the increased damage of DNA, lipids and proteins of the mitochondria as postulated by the free radical theory of aging.

• Content Type Journal Article
• Category Research article
• Pages 1-9
• DOI 10.1007/s10522-012-9372-9
• Authors
  • Ariane D. Minet, Department of Pathology, Laboratory for Molecular Physiology, Odense University Hospital, 5000 Odense, Denmark
  • Michael Gaster, Department of Pathology, Laboratory for Molecular Physiology and Department of Endocrinology, Odense University Hospital, 5000 Odense, Denmark

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729

Abstract  Natural products are the basis of many systems of traditional medicine and continue to provide sources for new drugs. Ethnobiological approaches to drug discovery that have proven productive in the past include the investigation of traditional medical literatures. This study describes a broadly applicable method for locating, selecting and evaluating citations in the traditional Chinese herbal medicine literature of the dynastic period (until 1911) for specific symptoms or disorders. This methodology is applied to evaluate multi-herb formulae for age-related dementia and memory impairment. Of the 174 multi-herb formulae located in the searches, 19 were for disorders broadly consistent with amnestic Mild Cognitive Impairment (MCI) and/or Age Associated Memory Impairment (AAMI). These appeared in books written between c. 650 to 1911. Of the 176 herbs that appeared in these 19 formulae, those with the highest frequencies were tabulated and hierarchical cluster analysis was undertaken. Chinese pharmacopoeias were consulted to determine the botanical identity of the herbs and also which herbs within the formulas were specific for memory disorders. This study found that the top ten herbs, in terms of frequency of inclusion in multi-herb formulae specific for age-related memory disorders, were all listed in the pharmacopoeias for memory disorders and these formed three clusters. The herbs identified in this study may warrant further experimental and clinical evaluation both individually and in combination.

• Content Type Journal Article
• Category Research Article
• Pages 1-14
• DOI 10.1007/s10522-012-9375-6
• Authors
  • Brian H. May, Traditional and Complementary Medicine Research Program, Health Innovations Research Institute; WHO Collaborating Centre for Traditional Medicine, School of Health Sciences, RMIT University, Bundoora, VIC 3083, Australia
  • Chuanjian Lu, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China
  • Louise Bennett, Pre-clinical and Clinical Health Substantiation, CSIRO Food and Nutritional Sciences, Werribee, VIC, Australia
  • Helmut M. Hügel, School of Applied Sciences [Applied Chemistry], RMIT University, Melbourne, VIC, Australia
  • Charlie C. L. Xue, Traditional and Complementary Medicine Research Program, Health Innovations Research Institute; WHO Collaborating Centre for Traditional Medicine, School of Health Sciences, RMIT University, Bundoora, VIC 3083, Australia

• Journal Biogerontology
• Online ISSN 1573-6768
• Print ISSN 1389-5729