02873nas a2200325   4500008004100000022001400041245012300055210006900178260006700247300001200314490000700326520171600333653003602049653001002085653002702095653001102122653001402133653001302147653001502160100002502175700002102200700002102221700002702242700003902269700002302308700003602331700002502367700002402392856013102416       2015                        eng d  a1474-971800aRifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans0 aRifampicin reduces advanced glycation end products and activates  a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJUN  a463-4730 v143 a<p>Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MSE, we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.</p>10aadvanced glycation end products10aaging10aCaenorhabditis elegans10aDAF-1610aGlycation10alifespan10arifampicin1 aGolegaonkar, Sandeep1 aTabrez, Syed, S.1 aPandit, Awadhesh1 aSethurathinam, Shalini1 aJagadeeshaprasad, Mashanipalya, G.1 aBansode, Sneha, B.1 aSampathkumar, Srinivasa-Gopalan1 aKulkarni, Mahesh, J.1 aMukhopadhyay, Arnab  uhttps://library.ncl.res.in/content/rifampicin-reduces-advanced-glycation-end-products-and-activates-daf-16-increase-lifespan-002720nas a2200289   4500008004100000022001400041245015100055210006900206260008100275300002200356490000700378520163500385653001302020653001402033653001402047653002102061653001002082653002202092100003902114700002502153700002502178700002002203700002302223700002902246700002502275856013002300       2016                        eng d  a1542-641600aTargeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of beta-hemoglobin for better diagnostics in diabetes0 aTargeted quantification of N1carboxymethyl valine and N1carboxye  a236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLANDbBIOMED CENTRAL LTDcMAR  aArticle Number: 70 v133 a<p>Background: N-1-(Deoxyfructosyl) valine (DFV) beta-hemoglobin (beta-Hb), commonly referred as HbA1c, is widely used diagnostic marker in diabetes, believed to provide glycemic status of preceding 90-120 days. However, the turnover of hemoglobin is about 120 days, the DFV-beta-Hb, an early and reversible glycation product eventually may undergo irreversible advanced glycation modifications such as carboxymethylation or carboxyethylation. Hence quantification of N-1-(carboxymethyl) valine (CMV) and N-1-(carboxyethyl) valine (CEV) peptides of beta-Hb would be useful in assessing actual glycemic status. Results: Fragment ion library for synthetically glycated peptides of hemoglobin was generated by using high resolution-accurate mass spectrometry (HR/AM). Using parallel reaction monitoring, deoxyfructosylated, carboxymethylated and carboxyethylated peptides of hemoglobin were quantified in clinical samples from healthy control, pre-diabetes, diabetes and poorly controlled diabetes. For the first time, we report N-1-beta-valine undergoes carboxyethylation and mass spectrometric quantification of CMV and CEV peptides of beta-hemoglobin. Carboxymethylation was found to be the most abundant modification of N-1-beta-valine. Both CMV-beta-Hb and CEV-beta-Hb peptides showed better correlation with severity of diabetes in terms of fasting glucose, postprandial glucose and microalbuminuria. Conclusions: This study reports carboxymethylation as a predominant modification of N-1-beta-valine of Hb, and quantification of CMV-beta-Hb and CEV-beta-Hb could be useful parameter for assessing the severity of diabetes.</p>10aDiabetes10aDiagnosis10aGlycation10aGlycemic control10aHbA1c10aMass spectrometry1 aJagadeeshaprasad, Mashanipalya, G.1 aBatkulwar, Kedar, B.1 aMeshram, Nishita, N.1 aTiwari, Shalbha1 aKorwar, Arvind, M.1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J.  uhttps://library.ncl.res.in/content/targeted-quantification-n-1-carboxymethyl-valine-and-n-1-carboxyethyl-valine-peptides-beta