Immunosenescence: Investigating molecular mechanisms and their impact on diseases

May 17, 2023

Immunosenescence, the age-related decline in immune function, is associated with increased susceptibility to infections, reduced effectiveness of vaccinations, earlier onset of age-related diseases, and the development of neoplasms. Ageing organisms exhibit a chronic state of inflammation known as inflammaging, characterised by elevated levels of pro-inflammatory markers. This persistent inflammation is a key factor contributing to age-related diseases. Immunosenescence is characterised by various notable features, including thymic involution, imbalances in the ratio of naïve to memory cells, disrupted metabolism, and epigenetic changes.

The premature ageing of immune cells is mediated by disturbed T-cell populations and chronic exposure to antigens. As a consequence, senescent immune cells develop a pro-inflammatory senescence-associated secretory phenotype that further exacerbates inflammaging. Although the specific molecular mechanisms underlying immunosenescence require further investigation, it is widely acknowledged that senescent T cells and inflammaging play pivotal roles in this process.

Efforts to counteract immunosenescence involve exploring interventions targeting cellular senescence and the metabolic-epigenetic axes in order to mitigate its effects. In recent years, the impact of immunosenescence on cancer development has gained attention. However, the study reported that due to the limited involvement of elderly patients in clinical trials, the exact influence of immunosenescence on cancer immunotherapy remains unclear.

To gain a better understanding of immunosenescence and its implications for cancer and other age-related diseases, further research is necessary. While some clinical trials and drugs have shown promising results, it is crucial to investigate the role of immunosenescence in these conditions to develop more effective strategies for treatment and prevention.

Ageing and immunity: The link between immunosenescence and health


Here are our key takeaways from the article, Immunosenescence: molecular mechanisms and diseases

Increased cancer risk


The ageing of the population has become a significant concern due to people living longer lives.

However, this increase in life expectancy has also brought about some challenges.

One of these challenges is the higher risk of age-related diseases, such as tumours. As individuals age, their bodies become more susceptible to developing cancerous growths.

Additionally, older individuals may experience a decrease in the effectiveness of immunotherapy, which is a treatment that harnesses the power of the immune system to fight cancer. Moreover, there is an increased likelihood of cancer recurrence after treatment among the elderly population.

Immunosenescence and vulnerability


Immunosenescence is a term used to describe the decline and dysfunction of the immune system as a result of ageing.

This process is characterised by several factors that impact the immune system’s functioning. For instance, older individuals tend to have poor outcomes from vaccinations, meaning their immune response to vaccines is not as robust as that of younger individuals.

This reduced response to vaccines makes older people more susceptible to infections and diseases.

Furthermore, immunosenescence is associated with an increased risk of age-related illnesses and malignancies, including cancer.

Key hallmarks of immunosenescence


Immunosenescence is marked by several key hallmarks that collectively contribute to immune system decline. One of these hallmarks is thymic involution, which refers to the shrinking and decreased function of the thymus, an organ responsible for the development of T cells, a type of white blood cell that plays a crucial role in the immune response.

Another hallmark is the dysfunction of both the innate and adaptive immune systems. The innate immune system acts as the first line of defence against pathogens, while the adaptive immune system mounts a more specific and targeted response. With age, both of these systems become less efficient, leaving the body more vulnerable to infections and diseases.

Additionally, immunosenescence is characterised by inflammaging, a state of chronic low-grade inflammation that persists in older individuals.

Lastly, the accumulation of senescent cells, which are aged and dysfunctional cells that no longer divide or function properly, is also a hallmark of immunosenescence.

Dysfunction of T cells


Within the context of immunosenescence, T cells are of particular importance. T cells are a type of white blood cell that helps coordinate and regulate immune responses.

However, as individuals age, different types of dysfunctional T cells can emerge. These include exhausted, senescent, and aged T cells. Exhausted T cells have become “tired” and less effective in their ability to combat infections or cancer cells.

Senescent T cells have reached a state of irreversible cell cycle arrest and can no longer function optimally. Aged T cells refer to T cells that have naturally aged and undergone changes that diminish their effectiveness.

Excessive accumulation of senescent and aged T cells can lead to a decline in immune function, making older individuals more susceptible to infections and age-related diseases, including cancer.

Targeting immunosenescence mechanisms


It is crucial to understand the molecular mechanisms underlying immunosenescence and senescent T cells to develop more effective therapeutic strategies.

By gaining insights into these mechanisms, researchers can identify potential targets for intervention. One promising approach involves targeting the metabolic-epigenetic axis of immunosenescence and senescent T cells.

This means focusing on the interactions between cellular metabolism (how cells obtain and use energy) and epigenetic modifications (changes in gene expression patterns).

By manipulating these processes, it may be possible to enhance the effectiveness of current immunotherapy treatments and potentially extend life expectancy.

This research holds promise for improving the health outcomes of ageing individuals and combating age-related diseases.

Reference: Liu, Z., Liang, Q., Ren, Y. et al. Immunosenescence: molecular mechanisms and diseases. Sig Transduct Target Ther 8, 200 (2023).