title: Age-related changes of leptin and leptin receptor variants in healthy elderly and long-lived adults.
abstract: OBJECTIVE
  Aging is usually associated with hyperleptinemia and leptin resistance, both increasing the risk of age-related diseases. It was relevant to establish if healthily aging, non-obese individuals develop changes in leptin, the soluble leptin receptor (OB-Re), free leptin index (FLI), in methylation of the leptin receptor gene (LEPR) promoter, and in the expression of long (OB-Rb) and short (OB-Ra) leptin receptor isoforms.
  
  
  METHODS
  We analyzed these parameters in 38 young (aged 26.8 ± 3.6 years), 37 elderly (aged 64.7 ± 3.1 years) and 39 long-lived (aged 94.2 ± 3.7 years) healthy, non-obese Polish Caucasians.
  
  
  RESULTS
  In elderly men, the median concentration of leptin and the median FLI were significantly higher than in young men (P = 0.009 and P = 0.007, respectively), which was probably partly due to a higher mean body mass index of the elderly study participants. In peripheral blood mononuclear cells, the expression of functionally active OB-Rb did not depend on age or sex, whereas the expression of OB-Ra was lower in the elderly and long-lived groups than in the young group (P < 0.0001 and P = 0.002, respectively), mostly due to changes observed in women. Most likely, this age-related decrease was not due to hypermethylation of the LEPR promoter, as methylation of the +20 to +281 fragment of the CpG island did not change with age.
  
  
  CONCLUSIONS
  In healthy, non-obese individuals, only some elements of the leptin axis slightly change with age. On that basis, we suggest that proper function of this axis might be required for this particular phenotype of aging. The present results should, however, be replicated in prospective studies and in other ethnic groups.
authors.affiliation: Department of Geriatrics and Gerontology, Center of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Roszkowska-Gancarz
authors.forename: Marta
authors.initials: M
authors.lastname: Jonas
authors.forename: Magdalena
authors.initials: M
authors.lastname: Owczarz
authors.forename: Alina
authors.initials: A
authors.lastname: Kurylowicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Polosak
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Slusarczyk
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mossakowska
authors.forename: Monika
authors.initials: M
authors.lastname: Puzianowska-Kuznicka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D050171:Dyslipidemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018507:Gene Expression Regulation, Developmental; D064368:Healthy Volunteers; D006801:Humans; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020738:Leptin; D054411:Receptors, Leptin; D012313:RNA
keywords: free leptin index; healthy aging; leptin; leptin receptor isoforms