SIRT1 Anti-Aging Protein most commonly known for being activated by red wine can help Rejuvenate highly specialized cytotoxic T cells

- SIRT1 Anti-aging protein, more commonly known for being activated by red wine can now be targeted to rejuvenate cells in the immune system
- Anti-aging protein SIRT1 can affect highly specialized cytotoxic T cells
- Over the course of time, with repeated exposure to bacteria and viruses, these cells mature and eventually lose a protein called CD28
- As these cells get older and lose CD28 they become more toxic to their environment leading to various autoimmune and inflammatory diseases





"Over the course of a person’s life, with repeated exposure to bacteria and viruses, these T cells mature and eventually lose a protein called CD28," said Gladstone Senior Investigator Melanie Ott, senior author of the new study. "And as these cells get older, they become more toxic to their environment."
This aging process is accelerated by persistent viral infections, such as HIV and CMV (human Cyto Megalo Virus). In fact, HIV-infected patients accumulate mature cyto toxic T cells at a much younger age than an uninfected person.
"A higher number of mature cytotoxic T cells in the body has been associated with age-related, autoimmune, and inflammatory diseases," added Ott, who is also a professor in the Department of Medicine at the UC San Francisco. "We wanted to come up with a way to counteract this phenomenon."
When a young (or naive) T cell is in a resting state, it uses oxygen to "breathe". Once it is activated to defend the body against a bacteria or virus, it shifts into enhanced glycolysis and uses sugar to get an immediate boost in energy. This is useful to jump into action, but it isn’t sustainable for long-term performance.
As the cells age and lose CD28, they can shift into glycolysis much more quickly if breathing is inhibited. They also lose the anti-aging protein SIRT1. This becomes a problem, as it makes them more toxic to the cells around them.
They found that naive T cells have a high concentration of SIRT1. This stabilizes an entire mechanism that prevents the cells from entering glycolysis to use sugar as an energy source, and limits their toxic effects.
As the cells age, they lose SIRT1, which changes their basic metabolism. They can then rapidly shift into glycolysis and start producing more toxic proteins called cytokines, which could lead to inflammatory diseases.
Based on a better understanding of the crucial role played by SIRT1 in the aging of T cells, the researchers identified two potential new drug targets.
First, new drugs could be developed to strengthen SIRT1 to rejuvenate mature cytotoxic T cells or keep them from progressing too quickly into a highly toxic state.
"This could postpone the development of age-related diseases," said Mark Y. Jeng, the study’s other first author and former graduate student in Ott’s lab. "It could also help people with a weaker immune system fight infections or better respond to immune vaccination, such as seniors or chronically-infected patients."
Alternatively, drugs could be used to obtain the opposite effect and encourage the T cells to be more toxic. By temporarily making young T cells more aggressive and behave like mature cells, they could, for example, support an aggressive anti-tumor response or other immune therapeutic approaches.
Reference
-
An Anti-Aging Protein Could Be Targeted to Rejuvenate Immune Cells - (https://gladstone.org/about-us/press-releases/anti-aging-protein-could-be-targeted-rejuvenate-immune-cells)
Source-Eurekalert