For some strange reason, cancer holds the key to aging. When Elizabeth H. Blackburn and her colleagues won the Nobel Prize in Medicine in 2009 for the discovery of telomerase (an enzyme that lengthens the life of cells) they realized that cancer cells were the only ones that could use this enzyme ‘ miraculous’ to be immortal.
One of the causes of aging, in addition to the shortening of the length of telomeres (ends of chromosomes) is oxidative stress. The accumulation of reactive oxygen species causes DNA damage and also changes in the protein molecules and lipids of the cell. The cell eventually loses its functionality and dies.
Now, precisely at the German Cancer Research Center in Heidelberg, they have found a key protein in the aging process. It is a protein molecule called TXNIP (Thioredoxin Interactive Protein). This molecule is responsible for transforming reactive oxygen molecules from vital to harmful, thus speeding up or slowing down the aging process.
But wait, wasn’t oxidative stress a cause of aging? Do reactive oxygen molecules have any benefit in cells? That’s right: reactive oxygen species do more than just damage DNA. For example, they are essential for the T cells of the immune system to be activated.
And how does the body remove harmful oxygen species to utilize those that are ‘beneficial’? One way is its conversion from harmful to vital: thioredoxin-1 enzyme (TRX-1). TRX-1 has been shown to play a role in protecting DNA against oxidative stress and slowing down the aging processes. But the leading molecule in the study, which is its opposite (TXNIP), inhibits thioredoxin-1 and therefore ensures that reactive oxygen molecules are retained, accelerating aging.
Therefore, we could think that aging is precipitated by a set of reactive oxygen molecules, one ‘beneficial’ (TRX-1) and the other, harmful (TXNIP); in which the harmful ends up winning. The researchers hypothesized that the latter accelerates its production with age, boycotting the work of TRX-1 to protect against oxidative stress, and causing the aging of cells.
TXNIP, the aging molecule
To find out if more TXNIP is formed in the body over the years , they compared T cells from the blood of a group of volunteers over 55 with T cells from younger blood donors, who were between 20 and 25 years.
Finally, it turned out that cells from older subjects produce significantly more TXNIP. DKFZ scientists have also observed similar findings in other types of human cells and tissues.
The researchers also found that more TXNIP is produced in the Drosophila fly as age increases. To test whether TXNIP is actually responsible for aging, they bred flies that produce significantly more TXNIP than their relatives, as well as flies in which TXNIP synthesis is greatly reduced.
“The flies that produced more TXNIP lived much shorter on average, while the flies with less TXNIP had a longer average life,” summarizes Tina Oberacker, the researcher responsible for the fly experiments.
In fact, “TRX-1 and its opponent TXNIP remain almost intact in the course of evolution, hardly differing between flies and humans,” Krammer explains. If more TXNIP occurs with age, this means that TRX gradually disconnects with its protection function.
This leads to increased oxidative stress, which damages cells and tissues, eventually leading to their death.
Reference: Tina Oberacker, Jörg Bajorat, Sabine Ziola, Anne Schroeder, Daniel Röth, Lena Kastl, Bruce A. Edgar, Wolfgang Wagner, Karsten Gülow, Peter H. Krammer: ‘Enhanced expression of thioredoxin interacting protein regulates oxidative DNA damage and aging’ . FEBS Letters, 2018, doi: 10.1002 / 1873-3468.13156
