Telomeres, Epigenetics, and Aging: the new found complexities in your genes
Telomere length is associated with aging, this isn’t a new statement, but interestingly enough there is more to this story than just the size of your telomeres. Telomere lengths have now been shown to cause epigenetic changes, this new discovery may help explain the aging of cells and how they initiate and transmit disease.
The team found that the length of the endcaps of DNA — the bits that shorten every time genes duplicate — called telomeres, form loops that determine whether certain genes are turned off when young and become activated later in life, thereby contributing to aging and disease.
“Our results suggest a potential novel mechanism for how the length of telomeres may silence genes early in life and then contribute to their activation later in life when telomeres are progressively shortened. This is a new way of gene regulation that is controlled by telomere length,” said Dr. Jerry W. Shay.
Telomeres cap the ends of the cell’s chromosomes to protect them from damage. But as mentioned before, the telomeres become shorter every time the cell divides. Once they shorten to a critical length, the cell can no longer divide and enters into a senescent or growth-arrest phase in which the cell produces different products compared to a young quiescent cell. Most research in this area has focused on the role that the process plays in cancer, but telomere shortening also has been shown to influence which genes are active or silent.
The team found that even before the telomeres shorten to the critical length that damages the DNA, the slow erosion in length has an effect on the cell’s regulation of genes that potentially contributes to aging and the onset of disease.
The way the body reads genes is called epigenetics and just like reading, your body does not read every gene the same way. For those of you who are not familiar with the field, genes are not read constantly every time, the comparison I like to use is that of a musician. If your genes were musical notes, it is the musicians’ job to figure out how to “play” those notes. It’s important to keep in mind than that, just as in music, the same song can sound completely different depending on the person — or even the mood of the person playing it.
The findings required the researchers to develop new methods for mapping interactions that occur near the endcaps and to use an extensive array of methodologies to verify the impact.
Specifically, the group showed that when a telomere is long, the endcap can form a loop with the chromosome that brings the telomere close to genes previously considered too far away to be regulated by telomere length. Once the telomere and the distant genes on the same chromosome are close to each other, the telomere can generally switch those genes off.
Conversely, when telomeres are short, the chromosome does not form a loop and the telomere can no longer influence whether target genes are switched on or off.
The researchers were able to identify three genes whose expression patterns are altered by telomere length but believe this number is the just the tip of the iceberg.
“We have developed the concept that telomere shortening could be used as a timing mechanism to respond to physiological changes in very long-lived organisms, such as humans, to optimize fitness in an age-appropriate fashion,” said Dr. Woodring E. Wright, co-author.
Discoveries like this are always incredible to me because the body has lots of hidden complexities, even from something seemingly simpler.
Jerome D. Robin,, Andrew T. Ludlow,, Kimberly Batten,, Frederique Magdinier,, Guido Stadler,, Kathyrin R. Wagner,, Jerry W. Shay,, & Woodring E. Wright (2014). Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances Genes & Development