effect on human longevity, possibly by modulating the risk of age-related disorders.

Background:

There is increasing evidence suggesting that genetics plays a significant role in human longevity. One or more genetic variants located on chromosome 9p21.3 and tagged by the single-nucleotide polymorphism (SNP) rs1333049 (G=C) are major risk factors for age-related disorders, such as acute myocardial infarction (AMI), stroke, and dementia. We hypothesized that this locus may have widespread effects on aging phenotypes and, as such, influences the ability to achieve a long and healthy life. 

Aim:

The aim of this study was to assess whether the rs1333049 polymorphism is associated with human longevity. 

Methods:

We tested the rs1333049 polymorphism in a sample of 80 healthy centenarians (39 men and 41 women aged 100-104), 218 patients younger than 40 who experienced an AMI, and a control group of 258 healthy individuals matched to AMI patients for age and sex. The frequency of the C allele of rs1333049 was significantly lower in centenarians compared to young controls, whereas AMI patients showed a higher frequency. After adjustment for gender and traditional factors, the C allele of rs1333049 remained significantly associated with a reduced likelihood to reach longevity: Odds ratio (OR) 0.64, 95% confidence interval (CI) 0.39-0.89, p < 0.01. Our data suggest that the rs1333049 polymorphism at 9p21.3 may influence successful human longevity possibly by modulating the risk of age-related disorders.

Results:

The frequency of the C allele of rs1333049 was significantly lower in centenarians compared to young controls, whereas AMI patients showed a higher frequency. After adjustment for gender and traditional vascular risk factors, the C allele of rs1333049 remained significantly associated with a reduced likelihood to reach longevity: Odds ratio (OR) 0.64, 95% confidence interval (CI) 0.39-0.89, p < 0.01.

Conclusions:

Our data suggest that the rs1333049 polymorphism at 9p21.3 may influence successful human longevity, possibly by modulating the risk of age-related disorders. Commercial DNA tests for this locus are already available and directly marketed to the general public. 

Background:

Successful aging is characterized by a marked delay or absence from major age-related diseases and disabilities, including acute myocardial infarction (AMI), stroke, and dementia, which respectively are the first, third, and fourth largest causes of mortality in Western countries. Genetic influences account for about a quarter of the variance in adult human life span, and it is likely that longevity-predisposing genetic polymorphisms may allow carriers to escape from these leading causes of mortality.

Discussion:

The interrelationships between successful aging and escape from age-associated illnesses, including atherothrombosis and dementia, have prompted growing research efforts in centenarian subjects aiming at entangling the biological and genetic pathways of human longevity. In the present work, we provide evidence that Caucasian centenarians have a lower prevalence of the risk allele of rs1333049 at the 9p21.3 locus. This finding, coupled with the high prevalence of this allele observed in patients with precocious AMI, further strengthens the concept that this variant rs1333049 is strongly associated with age-related disorders. The association of the C allele of rs1333049 remained significant after multiple adjustment for potential confounders. Therefore, this polymorphism appears to exert an independent effect on human longevity possibly by modulating the risk of age-related disorders. 

Methods:

Study participants: