Immunosenescence: impact of age on immunity
As humans are living longer, there is a dramatic shift in world demographics. Unfortunately, the rise in the number of individuals aged over 60 years does not necessarily correlate with an increase in healthy lifespan. With increasing age, the incidence and severity of infectious disease escalates, while the effectiveness of vaccination worsens.
‘Immunosenescence’ describes the diminished ability of the immune system to respond to infections. Close examination of the intrinsic defects of individual immune cells reveals the mechanisms of immunosenescence. Macrophages and neutrophils are part of the innate immune system, so make up the first line of defence against foreign antigens from bacteria and viruses. However, in elderly people, there is a defect in the activation of these cells through toll-like receptors, meaning that their bactericidal activity is limited. Dendritic cells have a vital role in presenting foreign antigens to cytotoxic T cells, but old age reduces their ability to traffic to lymph nodes where they would normally interact with naïve T cells, lowering their effectiveness at eliminating infection.
The microenvironment within secondary lymphoid organs such as lymph nodes, where innate and adaptive immune responses are generated, also plays an important role in immunosenescence. Aged stromal cells, altered cytokine secretion, and changes in the lymph node architecture all lead to a weaker immune system. Lymphatic endothelial cells (LECs) compose the lymphatic vessels which transport lymph carrying antigens and immune cells from infected tissues to the draining lymph nodes. Aged LECs become leaky, which makes them lose their ability to transport bacterial antigens to areas where an immune response can be conducted. A subtype of stromal cells in which I am particularly interested are fibroblastic reticular cells (FRCs). These cells form a reticular network which facilitates the interaction of T cells with dendritic cells in the lymph node. In my current research project, I am investigating how tumour cells might change FRCs in B cell lymphomas to accommodate immune evasion and metastasis. Aging might be one of the factors which helps tumour cells manipulate FRCs to their advantage. Indeed, development of many haematological cancers are age-related, so it is not unreasonable to suggest that aging of stromal cells in the microenvironment of lymphoid organs is one possible reason of pathogenesis.
Our understanding of cancer biology has improved substantially during recent years, giving momentum to cancer immunotherapy; the stimulation of the adaptive immune system to fight tumour antigens. Essentially, a healthy immune system can produce T cells that recognise and initiate an immune response against tumour antigens. However, immune functions alter in complex ways with age. These changes include the accumulation of cells which suppress immune functions, such as myeloid-derived suppressor cells. Thus, in order to increase the efficacy of cancer immunotherapy aimed at elderly patients, the properties of an aged tumour microenvironment must also be considered.
It is becoming increasingly clear that epigenetic changes due to environmental and lifestyle factors including the diet and physical activity of an individual contribute to their condition in old age. People at the time of the prophets lived for hundreds of years without developing disease due to the organic and active lives they led. Over time humans have altered the Earth for the worse, exposing us to radiation, increasing air pollution, and expanding the fast food market and the frequency of consumption of processed food. It has been scientifically proven that alcohol consumption and a diet low in fruit and vegetables are the most important aetiological agents of cancer after smoking. Moreover, a diet with a low intake of animal proteins, in particular pork, coupled with a higher consumption of vegetables, olive oil (instead of other saturated fats), and nuts have anti-inflammatory and anti-oxidant effects. The saying ‘you are what you eat’ therefore deserves a lot more credit than it gets. The naturally derived bioactive compounds found in natural foods have health promoting, disease preventing, and even medicinal properties. If only we could all live as naturally as our prophets Ibrahim, Nuh, and Idris aleyhisselam once did, perhaps old age would not come hand in hand with lethal disease.
