Ageing is interrelated with the development of immunosenescence. This article focuses on one of the cell sets of the adaptive immune system, T cells, and provides a review of the known changes in T cells associated with ageing. Such fundamental changes affect both cell molecular content and internal ordering. However, acquiring a complete description of the changes at these levels would require extensive measurements of parameters and, furthermore, important fine details of the internal ordering that may be difficult to detect. Therefore, an alternative approach for the characterisation of cells consists of the performance of physical measurements of the whole cell, such as deformability measurements or migration measurements: the physical parameters, complementing the commonly used chemical biomarkers, may contribute to a better understanding of the evolution of T-cell states during ageing. Mechanical measurements, among other biophysical measurements, have the advantage of their relative simplicity: one single parameter agglutinates the complex effects of the variety of changes that gradually appear in cells during ageing.

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.

A person's risk of developing cancer rises exponentially with age, an increase that is widely considered to result from cumulative exposure to mutagenic agents. However, cancer incidence rates decelerate and plateau beyond 85 years of age and numerous malignant pathologies peak in incidence during early or middle life, indicating an important role for additional factors in controlling the timing and nature of cancer development. Given that immune function is known to decrease with age, malignant neoplastic change may be induced by increased chronic infection and the onset of a pervasive low grade inflammatory environment. This article discusses in detail the ageing immune system's role in cancer pathogenesis and demonstrates that key polymorphisms coding for relatively low pro-inflammatory cytokine production act to protect some populations from age-induced neoplastic transformation.

Ageing is associated with multiple changes in many different components of the immune system. A healthy immune system exists in a state of balance between efficient effector responses against pathogens and tolerance to self antigens. This balance is changed with age; functions such as antigen recognition, phagocytosis, antigen presentation, chemotaxis, cytokine secretion and killing ability are all compromised. Aberrant cellular responses lead to an altered cytokine network with increases in inflammatory cytokines and decreases in anti-inflammatory cytokines leading to a pro-inflammatory state. Consequently older patients require extra care in diagnosis of infections as symptoms may be perturbed, resulting in unusual presentations of common conditions. The defects in immunity due to immunosenescence also mean that older patients require more care and screening than other patients in the same disease cohort. Though it is generally understood by clinicians that older patients are more at risk from multiple infections, the wider clinical effects of immunosenescence are less understood. The immune system is involved in several neurodegenerative conditions and the inflammatory conditions of immunosenescence may be a key factor in pathogenesis. Similarly, there is reason to believe that immunosenescence might be a key factor explaining the increased incidence of cancer in older age. With increasing understanding of the immune system's involvement in many of these pathological processes, and the contribution that immunosenescence makes to these, more efficient vaccines and novel therapies may be developed to prevent/treat these conditions.

Several immune functions are markers of health, biological age and predictors of longevity. A chronic oxidative and inflammatory state is the main cause of ageing and the immune system is involved in the rate of ageing. Thus, several murine models of premature ageing have been proposed owing to their early immunosenescence and oxidative stress, such as ovariectomised rats and mice, obese rats and anxious mice. In the last model, the most extensively studied by us, mice showing anxiety have an aged immune function and redox status as well as a shorter longevity in comparison with animals without anxiety of the same chronological age, being denominated prematurely ageing mice. A confirmation of the above is that the administration of diets supplemented with antioxidants improves the redox status and immune functions and increases the longevity of prematurely ageing mice. Antioxidant precursors of glutathione such as thioproline or N-acetylcysteine, which have a relevant role in ageing, have been the most widely investigated in adult prematurely ageing mice in our laboratory. In the present work, we have studied the effects of the ingestion for 5 weeks of a diet supplemented with 0·1% (w/w) thioproline+N-acetylcysteine on several functions of leucocytes from chronological old (69–73 weeks of age) prematurely ageing mice of two strains (Swiss and BALB/c). The results show an improvement of the immune functions, with their values becoming closer to those in adult animals (24±2 weeks). Thus, an adequate nutrition with antioxidants, even in aged subjects, could be a good strategy to retard ageing.

The reviewed literature indicates that, even in industrialised countries, the nutrition of mature and aged subjects is often inadequate (because of deficiency or excess), which may lead to premature or pathological senescence.

Recent nutritional research on ageing laboratory animals shows that dietary restriction may be the most effective procedure to achieve along and disease-free life span, probably owing to a better protection against mitochondria-linked oxygen stress. Likewise, the experimental and clinical work from many laboratories, including our own, indicates that age-dependent changes in the cardiovascular and immune systems are linked to oxygen stress and that an adequate intake of dietary antioxidants may protect those systems against chronic degenerative syndromes in the physiopathology of which reactive oxygen species (ROS) play a key role.

The extant data indicate that the antioxidant vitamins C and E are centrally involved in defending the above two systems against ROS attack. Moreover, recent research suggests that the glutathione-related thiolic antioxidants, thiazolidine carboxylic acid (thioproline) and N-acetylcysteine, as well as the phenolic liposoluble ‘co-antioxidants’ of Curcuma longa, may have a significant protective effect against age-related atherogenesis and immune dysfunction.

Key messages from this paper are the following. (1) It is generally accepted that oxygen free radicals released in metabolic reactions play a key role in the physiopathology of ‘normal ageing’ and of many age-related degenerative diseases. (2) Consumption of adequate levels of antioxidants in the diet is essential in order to preserve health in old age. (3) A certain degree of protection against atherogenesis and immune dysfunction may be achieved by preventing vitamin E deficiency and an excessive oxidation of the glutathione-supported thiol pool.