14 April 2003. In this month's Journal of Medical Genetics, a group of Italian researchers propose that there is a link between longevity and a single nucleotide polymorphism (SNP) in the promoter for the antiinflammatory cytokine interleukin-10 (IL-10). This may be particularly relevant to researchers of Alzheimer's and Parkinson's diseases, and other neurologic disorders that are age-related and exacerbated by inflammatory processes.
First author Domenico Lio and colleagues, working with Calogero Caruso at the University of Palermo, Italy, made the link after analyzing DNA samples from 174 centenarians and 227 nonrelated, geographically matched controls aged 22 to 60 years. Lio and colleagues found that centenarian men (n=72) more frequently had a guanosine base in position -1082 of the IL-10 gene, in contrast to the adenine that predominates in control subjects, but also, curiously, in centenarian women. The finding is statistically significant—46 percent of centenarian men vs. only 28 percent of controls had guanosine at this position in both copies of the gene. It is unknown, naturally, who among the control group will also live to see their one hundredth birthday. The authors did not report any SNP analysis of postmortem samples taken from people who died young, which could help strengthen the correlation between longevity and the SNP.
In-vitro data indicates that this adenine-to-guanosine transition in the promoter leads to greater expression of IL-10. Together, these findings lead the authors to speculate that the "antiinflammatory genotype may be highly advantageous in the last decades of life, owing to the chronic proinflammatory status, which develops in all the subjects with age." The authors also offer this "inflamm-ageing," as they call it, which is more evident in men, as an explanation for the sex difference in the SNP frequency.
Lio and colleagues also carried out SNP analysis on the tumor necrosis factor-α (TNF-α) promoter, where a similar A-to-G transition has been identified 308 base pairs upstream of the transcription start site, but found no correlation between this SNP and longevity.
The authors caution that their study has limitations, not least being that all the DNA samples were from Italian donors, so extrapolating these findings to other ethnic groups may be impossible. In Finland, for example, the frequency of the IL-10 SNP was found to be similar in nonagenarians and the rest of the population.—Tom Fagan.
Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafe M, Cavallone L, Marchegiani F, Olivieri F, Franceschi C, Caruso C. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10-1082 promoter SNP and its interaction with TNF-alpha-308 promoter SNP. J. Med. Genet. 2003;40:296-299. Abstract