What is immunosenescence? The age-related immune decline
Immunosenescence is the progressive, age-related deterioration of the immune system. This process affects both the innate and adaptive branches of immunity and contributes to a state of chronic inflammation known as 'inflammaging'. The reduced capacity of the aging immune system makes it less effective at responding to new threats. Several mechanisms underlie this decline, compromising immune function over time.
The hallmarks of immune system aging
Thymic involution
A key change in the aging immune system is the shrinking of the thymus, an organ vital for producing and maturing naive T-cells. The thymus involutes significantly by puberty, leading to a decrease in the output of new naive T-cells. Older adults rely on a less diverse pool of existing T-cells, hindering their ability to defend against new pathogens.
Changes in T-cells: Loss of diversity and function
As the thymus shrinks, the naive T-cell pool decreases, while antigen-experienced memory T-cells increase. This reduces T-cell diversity, making it harder to recognize new pathogens. Aging T-cells also exhibit impaired activation and proliferation, accumulate senescent cells that produce pro-inflammatory cytokines, and have altered cytokine production, contributing to inflammaging.
B-cell dysfunction
B-cells, responsible for antibody production, are also affected by age. In humans, there is a decline in memory B-cells and reduced antibody production with impaired affinity maturation, resulting in lower quality antibodies.
Chronic inflammation (Inflammaging)
Aging is marked by persistent, low-grade systemic inflammation called 'inflammaging'. This differs from acute inflammation and can arise from cellular senescence, mitochondrial dysfunction, and accumulating cellular debris. Inflammaging can exhaust the immune system, contribute to age-related diseases, and further impair immune cell function.
Comparison of immune function in young vs. older adults
| Feature | Young Adult | Older Adult |
|---|---|---|
| Thymus Function | High output of diverse, naive T-cells. | Significant involution; very low output of naive T-cells. |
| T-Cell Repertoire | Broad and diverse, with ample naive T-cells to combat new antigens. | Reduced diversity due to declining naive T-cell numbers and accumulation of memory cells. |
| B-Cell Response | Robust antibody production with high affinity maturation. | Reduced antibody production and lower affinity antibodies, potentially impairing vaccine response. |
| Vaccine Efficacy | Strong immune response and long-lasting protection. | Diminished immune response, often requiring higher doses or adjuvants for comparable protection. |
| Inflammation | Acute, localized, and effectively resolved. | Chronic, low-grade systemic inflammation ('inflammaging'). |
| Disease Susceptibility | Resilient to most infections and lower risk for chronic diseases. | Increased susceptibility to infections, cancer, and age-related diseases. |
Factors contributing to accelerated immunosenescence
Factors that can speed up immunosenescence include chronic infections like Cytomegalovirus (CMV), which exhaust T-cells. Nutritional deficiencies, poor diet, smoking, alcohol, stress, lack of exercise, obesity, and type 2 diabetes also contribute by increasing inflammation and impacting immune cell function.
Strategies to support immune health in older adults
While immunosenescence is part of aging, lifestyle and medical management can help. Strategies include a healthy diet rich in nutrients, regular moderate exercise, staying current with vaccinations (which may require specific formulations for older adults), managing chronic conditions, prioritizing sleep, and reducing stress.
Conclusion
The question of why do older people have weakened immune systems is explained by immunosenescence, a process involving thymic involution, reduced T-cell diversity, B-cell dysfunction, and chronic inflammaging. These changes increase susceptibility to infections, reduce vaccine effectiveness, and raise the risk of age-related diseases. However, lifestyle choices and health management can help older adults maintain immune resilience.
Keypoints
The age-related decline of the immune system, known as immunosenescence, involves reduced new T-cell production due to thymic involution, impaired T-cell diversity and function, and B-cell decline leading to poorer antibody quality. A state of chronic, low-grade inflammation ('inflammaging') further contributes to this decline. These factors collectively increase susceptibility to infections, reduce vaccine efficacy, and raise the risk of age-related diseases. Lifestyle choices and health management can help support immune health in older age. For more detailed information on T-cell aging, refer to {Link: Nature Immunology https://www.nature.com/articles/s41590-021-00927-z}.
