In the Vastness of the Genome
Conspicuous variants in a chain of events
Molecular pathways are intricately connected to each other through a vast network. Cellular actions are triggered, signals sent. Certain genes are switched on or off. The tumultuous events on these internal pathways also have an impact on when and how humans age. The scientists are intent on decoding those complex signal pathways.
TAGC - thymine, adenine, guanine and cytosine: The endless combinations of these four components are of paramount importance for our individual constitution. Their sequence determines how a biochemical command is given, why more plaque is deposited in the arteries at the end of a molecular interaction, or why aggressive free radicals are successfully kept in check. In the end, these are factors which influence our constitution - sick or healthy – and thus the way we age and how long we life.
This is why the molecular biologists of the research group scrutinize the TAGC sequences relentlessly that constitute the genetic material of the long-lived study participants. They are looking for the tiniest variations in the seemingly monotonous nucleotide patterns.
Age and longevity variants
The team of Stefan Schreiber and Almut Nebel can resort to a basically inexhaustible pool of individual TAGC combinations which the sequencing robots analyse: Thousands of individuals older than 92 years, about 700 of whom are even older than 100 years, have entrusted the scientists with their personal TAGC combinations through a blood sample. The scientists are now looking for genetic features the samples have in common and which could explain why these women and men, although they have been subjected to wars and epidemics, hunger and global economic crises, have aged so healthily. Noticeably, the only as yet decoded ageing variant within the APOE gene, which plays a role in fatal diseases such as Alzheimer's, is found very rarely in the genetic material of the study participants. In contrast to that, variations in the TACG sequence found rather more frequently in the genetic material of the study participants are candidate genes for longevity. Potentially, they may offer protection against organic degeneration and age-related diseases. It is those longevity variants the research group is looking for first and foremost.
Combing through the genome with high tech
It is only since very recently that scientists have been able to look deep into the genetic make-up of those long-lived individuals taking part in the study. The magic word is high throughput technology. The researchers design programme routines for powerful analysing robots which can systematically check the samples for candidate genes. The robots can even analyse genetic dispositions screening whole genomes. "With the human genome decoded and the human structural design available, we can now compare thousands of individuals ", explains the head of the institute Stefan Schreiber, who has identified disease genes for Crohn's disease, a chronic inflammation of the gut. "We have to find out what triggers diseases, then we know what protects against them." The secret of healthy ageing may be uncovered in that way as well.
Millions of SNPs - the genetic puzzle
A new generation of machines can investigate even the smallest elements of the genetic material, the Single Nucleotide Polymorphisms (SNPs).Those variations of individual genetic components may well contain the explanation for healthy ageing. Up to a million SNPs of each study participant are carefully examined by Schreiber's team with the help of gene chips hardly the size of a cigarette pack. The scientists compare the frequencies of those 1.000.000 SNPs between the long-lived participants and a control group of comparatively young participants 60 to 75 years of age. "The SNPs where we find a statistically significant difference in frequency between the long-lived and the younger control group are the interesting ones", states the scientist Almut Nebel.
