LEPR
Leptin receptor precursor (LEP-R) (HuB219) (OB receptor) (OB-R) (CD295 antigen) [DB] [OBR]
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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. 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. 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. 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.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Body Mass Index
- Cross-Sectional Studies
- DNA Methylation
- Dyslipidemias
- Enzyme-Linked Immunosorbent Assay
- Female
- Gene Expression Regulation, Developmental
- Healthy Volunteers
- Humans
- Leptin
- Male
- Middle Aged
- Poland
- Prevalence
- Prospective Studies
- RNA
- Receptors, Leptin
- Reverse Transcriptase Polymerase Chain Reaction
- Young Adult
Keywords
- free leptin index
- healthy aging
- leptin
- leptin receptor isoforms
Longevity is commonly associated with good health and with delayed onset of age-related diseases with usually benign course. Leptin (LEP) significantly affects metabolism and numerous functions of the organism. To find out if extreme longevity and its phenotype are associated with genetic variants of leptin and leptin receptor ([[LEPR]]) genes, we analysed the frequencies of the -2548 G/A and 19 G/A LEP, as well as the K109R, Q223R, and K656N [[LEPR]] polymorphisms in centenarians and in control groups. The frequencies of the LEP and [[LEPR]] polymorphisms were tested by restriction fragment length polymorphism in 128 centenarians, 414 young controls (Y), 226 myocardial infarction (MI) patients, and 190 type 2 diabetes mellitus (DM2) patients. The GG genotype of the -2548 G/A LEP polymorphism was significantly more common in centenarians than in the Y, MI and DM2 groups (p = 0.048, p = 0.003, p = 0.049, respectively). In addition, the AA genotype of the K109R [[LEPR]] polymorphism was significantly less frequent in centenarians than in the Y, MI, and DM2 groups (p = 0.026, p = 0.013, and p = 0.001, respectively). We suggest that the leptin pathway plays a role in the regulation of longevity, possibly by modulating the risk of development of MI and of DM2.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Cross-Sectional Studies
- Diabetes Mellitus, Type 2
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genotype
- Humans
- Leptin
- Longevity
- Male
- Middle Aged
- Myocardial Infarction
- Polymorphism, Genetic
- Receptors, Leptin
- Young Adult