Immunosenescence is a hallmark of aging characterized by decline and/or dysfunction of the immune system. Immune dysregulation contributes to a chronic inflammatory process also known as inflammaging.
As biological females enter the menopausal stage of life, they experience wide fluctuations in a variety of hormones that perpetuate metabolic disturbance and immune dysregulation. These physiological changes predispose toward inflammatory disease, including osteoporosis and cardiovascular disease.
Menopause appears to impair T lymphocyte function, a key component of the adaptive immune system. T lymphocytes, contrary to B lymphocytes, do not produce antibodies. They are instead trained to detect proteins expressed by antigen-presenting cells that signal presence of a pathogen.
The T cell thereby serves the purpose of surveilling for cancerous or infected cells. Once identified, the T cell can either latch onto the antigen presenting cell to destroy it along with the pathogen within, or release cytokines which set off an immune cascade.
The key subsets of T lymphocytes include:
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T helper cells — CD4+ cells regulate the immune system by releasing chemical messengers. These signals raise defense by attracting and directing other immune cells.
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Cytotoxic or Killer T cells — CD8+ cells have the capacity to directly kill cells affected by viruses, bacteria, or cancer.
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Regulatory T cells — Necessary for a balanced immune response. They play a critical role in enabling the immune system to distinguish between self and non-self, keeping the peace and preventing autoimmunity.
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Memory T cells — As their name implies, these cells behave as an ongoing catalog of previous infections. They stick around considerably longer than other immune cells in order to facilitate a faster response to a repeated offender.
As you can imagine, diminished function of the T lymphocyte pool can potentiate compromised immunity, leading to heightened incidence of autoimmunity, chronic inflammation, and a weakened defense system.
One critical actor that has been uncovered as a player in menopausal decline of T lymphocyte activity is Heat Shock Protein-27 (HSPB1). HSPB1 is proposed to exhibit anti-inflammatory activity and protect cells against toxins and disease. As estrogen levels fall during the menopause transition, so does HSPB1, possibly explaining the correlated drop in T lymphocyte potency.
As a component of the cellular stress response, HSPB1 has also been found to behave as an exerkine owing to its release upon an exercise stimulus. This and other exerkines mobilize immune cells and positively influence the immune response. The extent of exerkine release following a bout of exercise is dependent on certain variables, including load, volume, and rest periods.
It is well established that exercise training throughout life is paramount to preserve health. Given the profound hormonal and correlated metabolic changes experienced by biological women in menopause, exercise is especially beneficial during and after this period.
High-load resistance training has been noted to generate a greater degree of mechanical stress which may serve to more potently upregulate HSPB1 expression. A recent randomized crossover trial demonstrated higher HSPB1 stimulation with a high-load (90% 1RM, 3 sets, 6 reps/set, 3-minute rest, 7 exercises) as compared to a low-load protocol (50% 1RM, 3 sets, 20 reps/set, 90-second rest, 7 exercises).
Additionally, the high load protocol elicited enhanced IL-10 expressing CD4+ T lymphocyte mobilization. Such mobilization may ameliorate age-related immune dysfunction. The authors suggested that internal load as assessed by ratings of perceived exertion and lactate production is a better indicator of T lymphocyte trafficking than external load.
To evoke the most robust T lymphocyte mobilization, it appears important to achieve high levels of exertion and near momentary concentric failure. Higher force contractions that generate more mechanical tension seem to influence HSP27 independent of volume. Greater phosphorylation of HSPB1 induced by the high load protocol further potentiated its role in autophagy, apoptosis inhibition, and regulation of oxidative stress.
In summary, high load training may specifically target an anti-inflammatory subset of CD4+ T cells as compared to low load training. Collectively, the physiological changes of increased phosphorylated HSBP1 and IL-10 expressing CD4+ T lymphocytes after high load training confer an adaptive, anti-inflammatory immune response.
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