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How does mTOR signaling contribute to age-related decline in immune function?

mTOR (mechanistic target of rapamycin) signaling is a crucial pathway that regulates various cellular processes, including growth, metabolism, and immune function. In the context of aging, dysregulation of mTOR signaling has been implicated in the decline of immune function, which is a hallmark of aging.

1. mTOR signaling and immune cell senescence

One way in which mTOR signaling contributes to age-related decline in immune function is through the promotion of immune cell senescence. Senescence refers to a state of irreversible cell cycle arrest that is accompanied by various changes in cellular function. In the immune system, senescent cells accumulate with age and exhibit reduced proliferative capacity and altered functional properties.

mTOR signaling plays a role in driving immune cell senescence by promoting cellular senescence pathways, such as the activation of p53 and p16INK4a. Activation of mTOR signaling leads to increased production of reactive oxygen species (ROS) and DNA damage, which can trigger senescence in immune cells. Additionally, mTOR signaling inhibits autophagy, a cellular process involved in the removal of damaged proteins and organelles, further contributing to immune cell senescence.

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2. mTOR signaling and immunosenescence

Immunosenescence refers to the age-related decline in immune function, characterized by reduced immune response and increased susceptibility to infections and diseases. Dysregulation of mTOR signaling has been implicated in the development of immunosenescence.

mTOR signaling influences the differentiation and function of immune cells, such as T cells and natural killer (NK) cells. In aging individuals, mTOR signaling is often hyperactivated, leading to altered T cell and NK cell function. Hyperactivation of mTOR signaling promotes the differentiation of T cells into effector cells, which are less capable of mounting an effective immune response against pathogens. Additionally, mTOR signaling inhibits the function of regulatory T cells, which play a crucial role in maintaining immune homeostasis.

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3. Targeting mTOR signaling for immune rejuvenation

Given the role of mTOR signaling in age-related decline in immune function, targeting this pathway has emerged as a potential strategy for immune rejuvenation. Inhibition of mTOR signaling using rapamycin, a drug that specifically targets mTOR, has been shown to improve immune function in aged individuals.

Rapamycin treatment has been found to enhance the function of immune cells, restore immune cell homeostasis, and reduce the accumulation of senescent immune cells. Furthermore, rapamycin treatment has been shown to increase the lifespan and improve healthspan in various model organisms, suggesting its potential as an anti-aging intervention.

In conclusion, mTOR signaling plays a significant role in the age-related decline in immune function. Dysregulation of mTOR signaling contributes to immune cell senescence and immunosenescence, leading to reduced immune response and increased susceptibility to diseases. Targeting mTOR signaling holds promise for immune rejuvenation and potentially extending healthy lifespan.

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Keywords: immune, signaling, function, senescence, decline, related, rapamycin, cellular, immunosenescence