Who's gonna live the longest?

Extreme longevity is associated with a select group of genetic markers, according to a new study of centenarians, people living at least 100 years. Using these markers, researchers can predict a person's ability to become a centenarian with 77 percent accuracy.


The study chose 1000 non-related Caucasian centenarians and super-centenarians (those living 110 years or longer) from the New England Centenarian Study, which has been following people since 1995. The centenarians were compared to younger Caucasians with similar genetic backgrounds.

The researchers compared the frequency of 300,000 single-nucleotide polymorphisms (SNPs) in both groups, then looked for the SNPs that appeared most unique to the centenarians. They sequentially added additional markers down the line, increasing the specificity and sensitivity of the prediction algorithm until the results plateaued. Ultimately, the algorithm contained 150 SNPs that predicted a person's chances of reaching 100 with 77 percent accuracy.

The team is developing a software program for use by other researchers, companies, and individuals to analyze a genetic sequence and determine the likelihood of extreme longevity.

Less than half of the SNPs were located in areas associated with functioning genes. Some linked to the insulin pathway, some to genes associated with Alzheimer's disease (including the ApoE4 gene variant, which is a genetic risk factor for the disease) and dementia. Many of the SNPs point to more basic biological processes, such as chromosomal instability, muscle function and control of the immune system.

Of course, the researchers could only compare centenarians to younger controls, some of whom may eventually become centenarians themselves. However, given that it is such a rare trait -- only one in six thousand people reaches 100 or older -- the researchers said this potential confounder likely had minimal impact on the findings.

The centenarians were placed into smaller groups based on their SNP profiles. Some of the groups showed special characteristics, like those who survive the longest or those with the most delayed onset of age-related diseases. There was one cluster of centenarians that did not carry many of the SNPs associated with longevity. These could be people who lived really healthy lives, or harbor rare variants linked to longevity, the authors suggested.

Even though the centenarians survived so long, the researchers found that they have similar levels of a large set of disease-associated genetic risk factors as the controls, including risk factors for Alzheimer's, diabetes, and cardiovascular disease. This seems to indicate that long-life indicators also somehow mask disease traits.
P. Sebastiani,N Solovieff, A Puca, SW. Hartley, E Melista, S Andersen, DA. Dworkis, JB. Wilk, RH. Myers, MH. Steinberg, M Montano, CT. Baldwin, TT. Perls. "Genetic signatures of exceptional longevity in humans,"ScienceExpress, July 2010.

There is an online calculator that says I will live to 94, like my maternal grandmother!  And if I worked less and gave up coffee, that would probably increase by a number of years...I really need to do 23andme and check out my SNPs.  Let me know if you hear of any future deals with them! 

Science...It works, Bitches!

It's time to finally put aside the car religious fish symbols and the darwinian fish with feet.  Recent work is elucidating one of the crucial juicy mysteries in evolutionary biology: how did fins become limbs?


Published online at Nature, a team of researchers describe 2 proteins essential to fin development in bony fishes and the loss of which may have been a key step in the evolution of tetrapods (4-legged vertebrates).  During a routine screen for genes involved in fin regeneration in the zebrafish labs of Marie-Andree Akimenko and Marc Ekker at the University of Ottawa in Canada, the team noted a remarkable pattern among two of many unknown genes revealed by the screen: a unique and specific localization along the early median fin fold, which runs along a fish's back, and in the pectoral fin buds, fins that grow on each side of the fish's body behind the gills.  This gene expression pattern suggests the proteins are structural components of actinotrichia, the thin, rigid fibrils that form the scaffold of developing bony fins.  The team named the proteins actinodin 1 and 2 (And1, And2) and noted that along with related genes from a database, and3 and and4, were entirely absent in tetrapods.


Using morpholinos (molecules that transiently silence gene expression) to knock down these genes, and1 and and2, the team discovered that the genes are partly redundant, but necessary for fin formation.  If only one of the genes was knocked down, fin development was normal.  However, if both genes were knocked down, actinotrichia didn't form and thus there was no regional recruitment of mesenchymal cells (fin bone precursors).  Other gene expression patterns important for fin patterning in the region were also extensively disrupted during the double knockdown, including those for fibroblast growth factor and sonic hedgehog.  Interestingly, the knockdown gene expression profile in the zebrafish, is highly similar to experimental chick and mouse mutants called Gli3, which results in polydactyly (the presence of numerous extra digits).  Even more noteworthy, one of the earliest aquatic tetrapods, Acanthostega, had 8 digits on each hand, which may indicate that loss of actinotrichia in ancestral tetrapods may have been conducive to limbs resembling polydactyly.


Their conclusion: "The loss of formation of actinotrichia during evolution may have induced profound changes in the morphology of the adult pectoral fins that perhaps led to short appendages without lepidotrichia and to gene expression profiles conducive to polydactyly in the earliest tetrapod species. Thus, the loss of actinotrichia may have contributed to the evolutionary transition from fin to limb."


The team's next steps are to use alternative methods of gene silencing of and1 and and2 (remember that morpholinos are only transient silencers) to see whether the fin ray will develop and what it will look like (perhaps a limb with multiple digits?!).  The team may also introduce the gene into tetrapod species and see if they can cause fins in normally limbed animals.

Dreams of Autotrophic Humans

For years I've thought about genetically modifying humans into autotrophs to solve our worries about food production, animal rights, etc. "But wait, I love food" you say. Well, two options, either we also alter the hardwiring in your brain that directly links food to hedonic pleasure and reward, such that you no longer crave food and instead seek sunshine with the same fervent, or we supplement our autotroph-abilities with minimal food, little flavor pills to satisfy our food urges if you will. In all likelihood we would not be 100% efficient in converting available light energy into food (would we all need to start (?) running around naked, to maximize skin exposure to sunlight first of all...) See a friend's calculations on the upper bound of energy production by a human-plant.   In reality, we would likely have to supplement with food anyway.  Still, if would be rad. Think Avatar in green, rather than blue.  Regardless of implausibility of suggested modifications, autotrophs rule!

Part animal-part plant, we are that much closer to making green humans that photosynthesize rather than eat. Go Autotrophs!  See the actual science paper, a Wired post, a New Scientist post.