mTORC1 inhibition may improve T lymphocytes affected by aging
F Asghari1, M H Karimi2,3, A A Pourfathollah1
1Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Background:
Due to the increase of the elderly's population and related social and economic problems, it is very important to provide strategies on health. In this regard, induction of T lymphocytes responses, the most important cells of the immune system, may be a good approach. Among different agents considered as antiaging factors, mTORC1 pathway inhibitors are significant. So, the purpose of this study was to evaluate the effect of two mTORC1 inhibitors, Everolimus and Metformin, on age-related features of activated T cells.
Materials And Methods:
Optimum doses of drugs was determined with evaluating the effect of treatments on IL-2 gene expression. T cells isolated from old and young mice were treated with drugs and PHA. IL-2 production was evaluated by ELISA. Also, the expression of CD28, PD-1, and KLRG-1, proliferation, and intracellular oxidative stress were assessed by flow cytometry-based assays, phenotyping, CFSE, and DCF-DA assay respectively.
Results:
Both drugs increased IL-2 production in the T cells of old mice. Also, using drugs especially Metformin could improve age-related phenotypical markers and increase the proliferation of T cells of old mice significantly. In addition, Metformin and Everolimus reduced intracellular oxidative stress in aged cells. However, the effect of both drugs on the T cells of young mice wasn't significant or was in opposite to the results of old mice T cells.
Discussion:
In line with studies noting mTOR inhibitors as antiaging drugs, Metformin and Everolimus may improve T cells affected from aging in vitro, and a decrease in intracellular oxidative stress may be one of their mechanism of function.
Insights
Metformin and Everolimus, mTORC1 inhibitors, can improve aging T cells by reducing oxidative stress and enhancing immune responses. These findings suggest potential anti-aging strategies for the immune system in elderly populations.
Area of Science:
- Immunology
- Gerontology
- Pharmacology
Background:
- Aging populations present significant social and economic challenges, necessitating health strategies.
- Enhancing T lymphocyte responses is a key approach to combat age-related immune decline.
- mTORC1 pathway inhibitors are recognized for their anti-aging potential.
Purpose of the Study:
- To investigate the effects of Everolimus and Metformin, two mTORC1 inhibitors, on age-related characteristics of activated T cells.
Main Methods:
- Determined optimal drug doses via IL-2 gene expression.
- Treated T cells from old and young mice with drugs and PHA.
- Assessed IL-2 production, CD28/PD-1/KLRG-1 expression, proliferation, and oxidative stress using ELISA and flow cytometry.
Main Results:
- Both drugs boosted IL-2 production in aged T cells.
- Metformin significantly improved age-related T cell markers and proliferation in older mice.
- Metformin and Everolimus reduced intracellular oxidative stress in aged T cells, with minimal effects on young cells.
Conclusions:
- Metformin and Everolimus show potential as anti-aging agents for T cells in vitro.
- Reduced intracellular oxidative stress is a likely mechanism for the observed anti-aging effects.
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