title: Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.
abstract: Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose.
  
  
  
  This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used in management of aging.
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Rubina S
authors.initials: RS
authors.lastname: Kazi
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Reema M
authors.initials: RM
authors.lastname: Banarjee
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Arati B
authors.initials: AB
authors.lastname: Deshmukh
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Gouri V
authors.initials: GV
authors.lastname: Patil
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Mashanipalya G
authors.initials: MG
authors.lastname: Jagadeeshaprasad
authors.affiliation: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: mj.kulkarni@ncl.res.in.
authors.forename: Mahesh J
authors.initials: MJ
authors.lastname: Kulkarni
mesh_terms: D019069:Cell Respiration / Q000187:drug effects; D002909:Chronobiology Phenomena; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine
keywords: Aging; Glucose; Glycation; Mass spectrometry; Proteomics