So what is a SNP - a single nucleotide polymorphism - and why should you care? A quick definition:

A single nucleotide polymorphism (SNP, pronounced snip), is a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome (or other shared sequence) differs between members of a species (or between paired chromosomes in an individual). For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles : C and T. Almost all common SNPs have only two alleles.

Remember that a single gene is thousands of nucleotides long; SNPs are tiny differences considered in that scheme. However, in the same way that researchers - against initial skepticism - have been turning up single gene mutations that cause longevity for some time now, the community is starting to build the case for single SNPs that confer longevity benefits.

The common germline Arg72Pro polymorphism of p53 and increased longevity in humans:

A well known functional SNP in the tumor suppressor TP53 gene leads to increased longevity: in the Danish general population (n = 9219) homozygotes for the minor allele versus homozygotes for the major allele had an increase in median survival of 3 years. This is partly explained by increased survival after development of cancer or other diseases, in accordance with the observation that this Arg72Pro substitution in the p53 protein has important influence on cell death via increased apoptosis. Thus, the increased longevity may be due to a generally increased robustness after a diagnosis of any life-threatening disease.

In contrast to widespread skepticism on the importance of SNPs in humans, this gain-of-function p53 SNP of importance for cell repair mechanisms has a profound influence on longevity.

"Profound" here is in comparison to most examined SNPs, which appear to cause no meaningful differences. I imagine there will be other longevity SNPs uncovered in the future - there are tens of millions identified so far, and only a small fraction well studied. This particular SNP is another confirmation of the potential of p53 engineering for longevity:

• A New Look At p53, Cancer and Aging
• 50% Maximum Life Extension in Mice Via p53 and Telomerase

p53-related engineering looks to have at least as much potential as therapies based on the biochemistry of calorie restriction - which is to say not so much potential if you're already old. This is all about slowing rates of aging, not repairing the damaging of aging. This is why I favor quite different approaches to the engineering of human longevity.

At the end of last year, during the very successful Methuselah Foundation donation drive, I said:

The Longevity Meme Folding@Home team has been steadily rising through the ranks since its inception, thanks to the volunteer efforts of the many team members. The team is closing in on rank 200, a point that has been marked as a milestone for while. The lower ranks are a tough slog, but the team has been doing well - growing and producing results.

I have decided that the best thing to do to mark the passage of rank 200, rather than send out another round of Longevity Meme tchotchkes, is to donate a chunk of change to the Methuselah Foundation, where it can be put to good use in advancing longevity science. Here is my incentive for the team: pass rank 200, and stay beneath that level for a week, and I'll donate $1000 in support of Strategies for Engineered Negligible Senescence (SENS) research carried out by the Foundation.

The team recently steamed past rank 200 and, judging by the stats for surrounding teams, sub-200 ranks are here to stay. Please do drop by the Immortality Institute discussion thread for the Longevity Meme Folding@Home team to congratulate the volunteers. Congratulations all round, in fact!

I'll shortly be writing that check to fund a little more of the Methuselah Foundation's longevity science - and I hope that some of you folk decide to do the same this year. Don't forget that donations to SENS research are presently tripled by matching funds from Ryan Scott and Peter Thiel; my $1000 check will send $3000 to the researchers working on the LysoSENS and MitoSENS projects.

You might want to take a look at last month's update from the Foundation on the money rolling in and the new longevity research rolling out - things are moving along very nicely, and we hope to see even more progress in 2008.