Veronika V. Nesterova, Polina I. Babenkova, Anna A. Brezgunova, Natalia A. Samoylova, Irina S. Sadovnikova, Dmitry S. Semenovich, Nadezda V. Andrianova, Artem P. Gureev, Egor Y. Plotnikov
{"title":"β-羟丁酸对年轻大鼠和老年大鼠组织中线粒体生物生成、氧化应激和炎症标志物的影响差异。","authors":"Veronika V. Nesterova, Polina I. Babenkova, Anna A. Brezgunova, Natalia A. Samoylova, Irina S. Sadovnikova, Dmitry S. Semenovich, Nadezda V. Andrianova, Artem P. Gureev, Egor Y. Plotnikov","doi":"10.1134/S0006297924070149","DOIUrl":null,"url":null,"abstract":"<p>One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (<i>Ppargc1a</i>, <i>Nrf1</i>, <i>Tfam)</i>, quality control (<i>Sqstm1</i>), functioning of the antioxidant system (<i>Nfe2l2</i>, <i>Gpx1</i>, <i>Gpx3</i>, <i>Srxn1</i>, <i>Txnrd2</i>, <i>Slc6a9</i>, <i>Slc7a11</i>), and inflammatory response (<i>Il1b</i>, <i>Tnf</i>, <i>Ptgs2</i>, <i>Gfap</i>) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 7","pages":"1336 - 1348"},"PeriodicalIF":2.3000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Differences in the Effect of Beta-Hydroxybutyrate on the Mitochondrial Biogenesis, Oxidative Stress and Inflammation Markers in Tissues from Young and Old Rats\",\"authors\":\"Veronika V. Nesterova, Polina I. Babenkova, Anna A. Brezgunova, Natalia A. Samoylova, Irina S. Sadovnikova, Dmitry S. Semenovich, Nadezda V. Andrianova, Artem P. Gureev, Egor Y. Plotnikov\",\"doi\":\"10.1134/S0006297924070149\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (<i>Ppargc1a</i>, <i>Nrf1</i>, <i>Tfam)</i>, quality control (<i>Sqstm1</i>), functioning of the antioxidant system (<i>Nfe2l2</i>, <i>Gpx1</i>, <i>Gpx3</i>, <i>Srxn1</i>, <i>Txnrd2</i>, <i>Slc6a9</i>, <i>Slc7a11</i>), and inflammatory response (<i>Il1b</i>, <i>Tnf</i>, <i>Ptgs2</i>, <i>Gfap</i>) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. 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Differences in the Effect of Beta-Hydroxybutyrate on the Mitochondrial Biogenesis, Oxidative Stress and Inflammation Markers in Tissues from Young and Old Rats
One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam), quality control (Sqstm1), functioning of the antioxidant system (Nfe2l2, Gpx1, Gpx3, Srxn1, Txnrd2, Slc6a9, Slc7a11), and inflammatory response (Il1b, Tnf, Ptgs2, Gfap) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.
期刊介绍:
Biochemistry (Moscow) is the journal that includes research papers in all fields of biochemistry as well as biochemical aspects of molecular biology, bioorganic chemistry, microbiology, immunology, physiology, and biomedical sciences. Coverage also extends to new experimental methods in biochemistry, theoretical contributions of biochemical importance, reviews of contemporary biochemical topics, and mini-reviews (News in Biochemistry).