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Oxidative stress makes cells and entire organisms to age,accumulation of reactive oxygen species causes damage to the DNA as well as changes in the protein molecules and lipids in the cell. The cell loses its functionality and dies. After a long time, the tissue suffers and the body ages.
Reactive oxygen species do more than just damage the body, they are essential for the T-cells of the immune system to become active. DKFZ researchers led by Krammer and Karsten Gülow have now discovered the key regulator that is responsible for shifting the sensitive balance from vital to harmful amounts of reactive oxygen molecules and thus accelerating the aging process: A protein molecule called TXNIP (thioredoxin-interacting protein).
Human body disposes harmful reactive oxygen species is their conversion by the enzyme thioredoxin-1 (TRX-1). TRX-1 has been proven to play a role in protecting DNA from oxidative stress and slowing down aging processes. Its antagonist TXNIP inhibits thioredoxin-1 and thus ensures that the reactive oxygen molecules are retained.
Researchers compared compared T cells from the blood of a group of over 55-year-old volunteers with the T cells of younger blood donors, who were between 20 and 25 years old. The cells of older participants produce significantly more TXNIP. The DKFZ scientists have also observed similar findings in other human cell and tissue types.
The researchers also found out that more TXNIP is produced in the fly Drosophila with increasing age. In order 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. Flies that produced more TXNIP lived on average much shorter, while flies with less TXNIP had a longer average life.
TRX-1 and its opponent TXNIP are highly conserved in the course of evolution; they hardly differ between flies and humans, the two proteins perform similar functions in flies and humans. If more TXNIP is produced with increasing age, this means that TRX is gradually switched off with its protection function. This leads to more oxidative stress, which damages cells and tissue and eventually causes them to die. TXNIP is a key regulator for aging, it is good to switch off TXNIP to delay aging. Similarly, aging can be accelerated TXNIP is produced.
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