The Longevity Gene?
This web page was produced as an assignment for an undergraduate course at Davidson College.
What We Hear
On August 28, 2001, CNN reported that "researchers have identified a region of a chromosome that they believe contains the genes responsible for longevity" (2001). Informed by Dr. Thomas Perls and Louis Kunkel and their study (Puca, Daly et. al, 2001), which was only published the day before, the article explains how the suspected region is on chromosome 4, which contains between 100 and 500 genes. However, it also mentions that this study is contrary to what most researchers believe, which is that as many as 1,000 genes influence aging in humans. Perls sites the odds as one in twenty that this kind of longevity would happen randomly with no genetic involvement. The researchers ended their study using data from 137 sets of two or more siblings. One of these siblings had to be at least 98 years old with at least one brother of 91 or older or one sister of 95 or older. By looking for identical regions of chromosomes among a large proportions of the siblings, the researchers were able to take the first step in identifying the longevity gene.
The Actual Study
Centenarians live longer, the researchers hypothesize, because their genetic makeup in conjunction with favorable environmental factors helps them to age more slowly than the general population, as well as to delay or escape typically "age-associated" diseases such as cardiovascular disease, stroke, diabetes, cancer, and Alzheimer's disease. To back up this hypothesis, a comparison of centenarians' siblings versus the siblings of a control group showed that the centenarians' siblings had a much greater chance of surviving to an extreme old age. Adding to this was the discovery of four families which all included many exceptionally old individuals.
Using 137 sibships and 308 individuals in the final analysis, the geneticists extracted DNA and ran it all in a genome-wide scan. The ages of the siblings (at least one male sibling 91 or older and/or a female sibling 95 or older) were chosen as such because they represented the 5% oldest individuals in US and Candian life tables.
Fig. 1. Multipoint lod scores for the genome-wide scan. Individuals in 137 sibships demonstrating exceptional longevity were genotyped at 400 marker loci throughout the genome. Scores are plotted as a function of specific markers. Chromosome number is designated at the top of each plot. The horizontal threshold lines on each graph represent MLS = 2.0, a score slightly higher than the average maximum score expected by chance once in a genome scan.
Figure courtesy of PNAS.
While this discovery is only the first in locating this particular gene of interest, many genetic mechanisms are believed to be responsible for centenarians' longevity. One necessary trait seems to be a relative lack of polymorphisms leasing to age-associated diseases. Another could be centenarians' ability to genetically control how fast they age and thus the impact on susceptibility to diseases associated with aging. There exists little possibility of this gene's locus being leading to one common disease. They suggest further studies with the same families in order to facilitate the cloning of a gene that may influence the ability to age well and achieve longevity. Identifying this gene should elucidate cellular pathways involved in the aging process.
(1) 28 August, 2001. Researchers narrow search for longevity gene. <http://www.cnn.com/2001/HEALTH/08/27/longevity.genes>. 31 August, 2001.
(2) Puca, Annibale A, Daly, Mark J., et al. 27 August, 2001. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proceedings of the National Academy of Sciences, Vol. 98:18. 31 August, 2001. <http://www.pnas.org/cgi/content/full/98/18/10505?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&titleabstract=longevity+gene&searchid=QID_NOT_SET&stored_search=&FIRSTINDEX=0>