Older people get sick more often due to a violation of the body’s tissues. Chronic inflammatory processes cause aging. Recent studies have shown that excessive inflammation suppresses the immune system in animals and humans. By eliminating the inflammation, you can improve the immune system.
This discovery is essential for the treatment of older people infected with the SARS-CoV-2 coronavirus. The coronavirus causes severe inflammation of the respiratory tract, which can be fatal for the elderly. Reducing inflammation can help boost the immune system of older people.
Initially a high level of inflammation in the elderly
People over 60 often have chronic inflammation that is not caused by a pathogen. Their serum levels of inflammatory markers are elevated:
- C-reactive protein (CRP);
- interleukin-6 (IL-6) and IL-8 cytokines.
Compared to the elderly, who do not have elevated levels of systemic inflammation, these people are more likely to experience weakness and early mortality.
Inflammation can cause a violation of the intestinal barrier function, obesity, accumulation of incorrectly folded proteins, as well as a violation of the removal of dying and dead cells from the body. As the body ages, each organ accumulates aging cells that no longer divide. These cells increase the level of inflammation.
Aging of lymphocytes and non-lymphoid cells
Cells of the immune system-lymphocytes – are also susceptible to aging. They stop dividing due to shortening of DNA sections at the ends of chromosomes (telomeres), DNA damage, changes in gene expression and cell phenotype, and disorders of the mitochondria – the energy centers of cells.
Aging non-lymphoid cells secrete:
- inflammatory cytokines;
- chemokines;
- growth factor;
- matrix metalloproteinases (MMP).
That is called the senescence-associated secretory phenotype (SASP). SASP can cause organ disorders during aging.
Anti-inflammatory drugs to strengthen the aging immune system
Inflammation is involved in the formation of the immune response. Excessive inflammation suppresses antigen-specific immunity (acquired). By removing dying and dead cells from the body, inflammation is reduced. Research in mice and humans has shown that severe inflammation reduces the effectiveness of vaccines, including against influenza. Inflammation during aging and its debilitating effect on the immune system can be eliminated with rapamycin, an mTOR protein inhibitor. Rapamycin enhances influenza-specific antibodies after vaccination against influenza.
With age, the immune system decreases. That leads to reactivation of the varicella zoster virus (VZV), which causes chickenpox in children and shingles in adults. An oral inhibitor of mitogen-activated protein kinase p38 (MAPK) enhances the response to chickenpox and reduces initial skin inflammation in the elderly by suppressing the influx of inflammatory monocytes.
A possible strategy for improving immunity in older adults is to reduce inflammation with a short course of mTOR or p38 MAPK inhibitors and other anti-inflammatory drugs, such as dexamethasone.
Elderly patients with severe COVID-19 have severe airway inflammation. This inflammation can reduce antiviral immunity. Therefore, the strategy of increasing immunity by reducing inflammation is especially crucial for the treatment of elderly patients with coronavirus.
Eliminating aging cells means boosting the immune system
With age, the number of aging cells increases. Aging cells accumulate in each organ and secrete pro-inflammatory mediators, which increases the level of inflammation. Therefore, another way to increase immunity and reduce inflammation may be to remove aging cells from the body.
The tissues of the body can be naturally cleansed of senescent cells. Aging cells Express signaling molecules-ligands. Ligands send a “kill me” signal, after which natural killer cells (NK cells) and cytotoxic T-lymphocytes kill these aging non-lymphoid cells. NK cells are lymphocytes that do not need to be sensitized with antigens to destroy infected and tumor cells, so they act faster.
If T and NK cells can eliminate aging cells, why do non-lymphoid aging cells accumulate during aging? One of the reasons is the age-related decline in immunity, which reduces the ability of immune cells to eliminate aging non-lymphoid ones. Another reason is that aging cells may avoid immune cleansing. In this case, the aging cells express “don’t kill me” signaling molecules and also secrete trap receptors that prevent cytotoxic T-cells from recognizing them.
A study on transgenic mice showed that removing aging cells eliminates age-related disorders in the organs. Senolytics – an anti-aging drug that can selectively eliminate aging cells is nowadays studying in mice and humans.
Causes of hyperinflammation in the elderly with coronavirus
Eliminating inflammation and clearing the body of cells that produce inflammatory mediators can improve health and immunity.
A possible cause of hyperinflammation in the elderly with COVID-19 is that aging cells suppress the immune response. The number of aging cells in the lungs increases with age. These cells can initiate an inflammatory cascade in elderly patients with COVID-19. Adipose tissue cells produce pro-inflammatory mediators and can also contribute to inflammation. It is crucial because obesity is a risk factor for COVID-19.
How are high baseline levels of inflammation and hyperinflammation related in the elderly with severe COVID-19? Aging cells and adipose tissue cells create an inflammatory phenotype that increases following inflammatory responses. During the immune response, monocytes from the bloodstream enter the skin of older people. Monocytes are cells of the immune system that can cause inflammation. Monocytes can also enter the lungs of patients with severe COVID-19 from the bloodstream. However, the high initial level of inflammation does not explain why severe COVID-19 destroys the body’s tissues. A possible cause is age-related changes in T-lymphocytes.
How to behave in old T-lymphocytes upon COVID-19
Older adults accumulate aging, highly differentiated T-lymphocytes. These old T-lymphocytes can destroy cells that Express “kill me” ligands (NKR). Inflammation increases the number of such cells. Old T-lymphocytes that infiltrate the lungs of patients with COVID-19 do not function well in an antigen-specific way. That happens due to inflammation, as well as the fact that old T-lymphocytes act like NK cells: they do not recognize specific antigens. Infiltration of inflammatory monocytes in the lungs of patients with COVID-19 triggers the expression of NKR ligands by non-lymphoid cells, which can be destroyed by infiltrating T lymphocytes. It causes damage to the respiratory tract tissues of patients with COVID-19.
Immune responses to SARS-CoV-2 infection in the elderly
In older people with SARS-CoV-2, highly differentiated T-cells can damage the lungs. Therefore, when studying immune responses in the elderly, it is vital to take into account the propensity to develop inflammatory responses in tissues and changes in the behavior of different populations of white blood cells. A high initial level of inflammation can initiate an inflammatory cascade that increases hyperinflammation that occurs in response to pathogens.
Inflammation has many consequences for patients with COVID-19. The accumulation of aging cells in the Airways of elderly patients can trigger an inflammatory cascade that suppresses T-lymphocyte responses to infected cells. Another consequence of inflammation is the expression of the NKR ligand by lung cells, which causes them to be destroyed by infiltrating T-lymphocytes.
Due to the high initial level of inflammation in the elderly, the effectiveness of vaccination is reduced. It is important to consider when developing a COVID-19 vaccine. A combination of anti-inflammatory and antiviral regimens may be required to treat patients with COVID-19 and vaccinate against coronavirus.
