It is now becoming apparent that the immune system undergoes age-associated alterations, which accumulate to produce a progressive deterioration in the ability to respond to infections and to develop immunity after vaccination, both of which are associated with a higher mortality rate in the elderly.
The decline in function of the immune system with age is termed immunesenescence. The role of the immune system is 3-fold: to protect the host from pathogens; to recognize “altered cells” such as cancers; and to do both of these things while not reacting to self-antigens. With aging each of these arms of the immune system is compromised. Immunity not only weakens in older age; it also becomes imbalanced. This affects the two branches of the immune system — “innate” immunity and “adaptive” immunity — in a double whammy of “immunosenescence.”
Inflammaging and Innate Immunity
The innate immune system is the first line of defense and is important for early defense against pathogens. The innate immune response consists of physical, chemical and cellular defenses against pathogens. With age, cells of the innate system, notably neutrophils and monocytes/macrophages, undergo changes that lead to compromised functioning of the immune system. Failure to curb the activity of innate immunity leads to inflammatory diseases, autoimmune diseases, atherosclerosis, neurodegenerative diseases and cancer.
Inflammaging (also known as inflamm-aging or inflamm-ageing) is a chronic low-grade inflammation that develops with advanced age. It is believed to accelerate the process of biological aging and to worsen many age-related diseases. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive.
After an initial infection or injury, younger people’s immune systems switch to an anti-inflammatory response. This does not appear to happen as effectively in older adults. This is due to the accumulation of aged, or “senescent,” immune cells. Senescent immune cells produce more immune signaling molecules called cytokines, which promote inflammation. Specifically, they churn out more interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). High levels of IL-6 and TNF-alpha have been linked to disability and mortality in older adults. They have a particularly strong association with type 2 diabetes, cardiovascular disease, neurodegenerative disease, and cancer.
Telomere Shortening
Telomeres are distinctive structures found at the ends of our chromosomes. They consist of the same short DNA sequence repeated over and over again. Telomeres are often compared to the plastic caps at the end of a shoelace, and in this analogy, the shoelace itself would represent a set of your DNA strands. The telomere keeps the strands of DNA from fraying and coming apart. Without telomeres, important DNA would be lost every time a cell pides (usually about 50 to 70 times). Over time (and also due to various lifestyle factors), the telomere degrades and shortens, which contributes to aging.
Age-related decline in immunity is characterized by stem cell exhaustion, telomere shortening, and disruption of cell-to-cell communication, leading to increased patient risk of disease. Recent data have demonstrated that chronic inflammation exerts a strong influence on immune aging and is closely correlated with telomere length in a range of major pathologies. The immune system is highly sensitive to shortening of telomeres as its competence depends strictly on cell renewal.
Aging and Adaptive Immunity
The function of adaptive immune responses is to destroy invading pathogens and any toxic molecules they produce. Through adaptive immunity, the immune system learns to recognize and neutralize particular pathogens. A type of immune cell known as a T cell plays a crucial role in adaptive immunity. In the course of an infection, “naïve” T cells learn to recognize the specific pathogen involved. They then differentiate into cells that are specialized to mount future immune responses against the same pathogen.
The total number of T cells remains constant throughout our lifetime, but the pool of naïve, undifferentiated cells steadily shrinks over the years, as more and more cells commit to tackling specific infections. As a result, the bodies of older adults become less able to mount effective immune responses to new infections. For the same reason, vaccinations provoke weaker responses from the aging immune system and, therefore, provide less protection.
Mitochondrial Damage in Inflammaging
A mitochondrion is a round to oval-shaped organelle found in the cells of almost all eukaryotic organisms. It produces energy, for the cell through a series of chemical reactions.
Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, ROS also serves as critical signaling molecules in cell proliferation and survival. Mitochondrial ROS production is a key antimicrobial function of specialized immune cells including macrophages and neutrophils. Accordingly, age-related impairment of mitochondrial function can significantly impair host immune responses. Increasing age is typically accompanied by decreased mitochondrial output of antimicrobial ROS together with a parallel increase in oxidative stress. It now seems that oxidative stress, mitochondrial damage, and cellular aging are intimately linked in multiple species including yeast.
Inflammaging and Coronavirus
The increased severity and mortality of COVID-19 infections in older inpiduals may be related to inflammaging. Inflammaging has many implications for COVID-19 patients. The accumulation of senescent cells in the respiratory tract of older patients may be involved in the initiation of an inflammatory cascade that could inhibit T cell responses to virally infected cells that are present. The search for an effective vaccine for COVID-19 should also consider the decreased vaccination efficacy in older inpiduals that may be associated with inflammaging.
Immune System Boosting Tips for Seniors
Although nothing can prevent aging, there are certain lifestyle changes a person can make to stay healthy into older age. Get plenty of sleep. Quit smoking. Spend time outdoors. Exercise has a profound effect on the immune system. Getting as much exercise as possible can slow or even reverse some of the effects of immunosenescence. Skeletal muscle produces a range of proteins called myokines that reduce inflammation and preserve immune function. The intensively and moderately active males produced more antibodies in response to vaccination than the least active males. The more active males had higher serum concentrations of antibodies to some flu strains even before they underwent vaccination.
Eating a healthy, nutrient-rich diet is another way to boost your immune system so that it can fight off viruses. This includes eating a diet rich in fruits and vegetables, which contain vitamins and antioxidants to promote good health. People who eat a Mediterranean diet are less likely to become “frail” in older age, such as by losing muscle strength, walking slowly, and tiring easily. The Mediterranean diet comprises: large amounts of fruit, leafy vegetables, and olive oil, moderate amounts of fish, poultry, and dairy and low amounts of red meat and added sugar. A Mediterranean diet is associated with low levels of inflammatory markers.
Maintaining a healthy weight. Although muscle plays a role in reducing inflammation in older adults, fat, or “adipose,” tissue may have the opposite effect. Normal aging often leads to weight gain, due to an accumulation of adipose tissue beneath the skin and around the organs. Adipose tissue may make a significant contribution to inflammaging. Up to 30% of the pro-inflammatory cytokine IL-6 in the bloodstream may originate from adipose tissue. Therefore, having obesity or being overweight in older age may significantly contribute to chronic inflammation The immune system of people with obesity may produce fewer antibodies in response to the flu vaccination.
Lower your stress level. Chronic stress can weaken the immune system further and make a person more susceptible to illness. To help reduce your stress level, set limitations and don’t be afraid to say no. Engage in activities that you find enjoyable and relaxing, such as reading or gardening. Practices that may reduce and manage stress include: yoga, massage and spending time pursuing hobbies.
By: Dr. Magdy Badran
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