Immunosenescence Mechanisms

Immunosenescence is the age-related deterioration of the immune system, characterised by diminished immune responses and increased susceptibility to diseases. This process is driven by various mechanisms, including thymic involution, inflammaging, cellular changes, stem cell exhaustion, genomic instability, and gut microbiome changes.

Thymic involution impacts the immune system's ability to respond to antigens, while inflammaging, a form of chronic inflammation, impairs immune function. Cellular changes, including metabolic adaptations and haematopoietic modifications, disrupt immune coordination. Stem cell exhaustion hinders tissue regeneration, and genomic instability and epigenetic alterations affect immune cell development and function.

Gut microbiome changes disrupt the gut-brain axis and trigger neuroinflammation, while mitochondrial dysfunction and circadian rhythm disruptions influence immune cell activation. The accumulation of senescent cells is a significant factor, and their removal with senolytics may slow ageing.

Immunosenescence is a complex process influenced by exposomal factors, including stress, diet, and lifestyle. Understanding these mechanisms is vital for developing therapies to treat age-related illnesses.

T Cells

T cells are a type of immune cell that play a crucial role in the body's immune response. They are affected by immunosenescence, which reduces the body's response and disease resistance. T cells are also affected by the Aryl Hydrocarbon Receptor (AHR), a receptor protein found within cells that plays a critical role in immune responses and tissue healing. Insufficient AHR activation can cause an immune system imbalance, leading to diseases.

Senolytics

Senolytics are a class of drugs that selectively eliminate senescent cells by inhibiting anti-apoptotic pathways. These drugs have shown promise in various age-related disease models, including cancer metastasis, fibrosis, atherosclerosis, liver cirrhosis, diabetes, sarcopenia, and osteoarthritis. However, challenges such as off-target toxicities and tissue atrophy require further research to establish safety and efficacy.

Geroscience and Ageing Mechanisms

Geroscience focuses on understanding ageing mechanisms and developing interventions to prevent age-related diseases. Key mechanisms include genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, and altered intercellular communication. Interventions like epigenetic reprogramming and partial reprogramming aim to reverse these changes and improve cellular function.

Exposome and Ageing

The exposome, encompassing external exposures, significantly influences ageing by impacting molecular and cellular damage. Factors like environmental pollutants, social conditions, psychological stressors, and diet modulate ageing processes.

Microbiome and Ageing

The gut microbiome plays a significant role in ageing, influencing inflammatory immunity, nutrient metabolism, and neuroprotection. Changes in microbiome composition with age act as potential biomarkers and targets for interventions.

Biological Age Testing

Biological age testing is a method of assessing an individual's physiological state, distinct from their chronological age. It aims to quantify the body's 'wear and tear' at a molecular level, offering insights into biological ageing and predicting mortality. Biological age tests use computational models, known as biological ageing clocks, to estimate an individual's biological age by analysing biomarkers such as DNA methylation and plasma proteins.

Interventions

Interventions targeting chronic inflammation and ageing include diet and lifestyle changes, probiotics and prebiotics, and senolytics and epigenetic therapies. These interventions aim to modulate the gut microbiome, reduce inflammation, and reverse age-related changes.

In conclusion, immunosenescence is a multifaceted process driven by various mechanisms. Understanding these mechanisms is crucial for developing effective treatments for age-related diseases and injuries. Further research is needed to translate these findings into effective clinical practices.