Immune system changes and immunosenescence

Author(s):  
Graham Pawelec ◽  
Ludmila Müller ◽  
Tamas Fülöp ◽  
Deborah Dunn-Walters

The immune system defends against infection, but older people paradoxically suffer not only from failing immunity resulting in increased susceptibility to infections and decreased responsiveness to vaccination, but at the same time increased inflammation and immunopathology accompanying immune responses. Interventions to reduce such deleterious effects while enhancing protective immunity are challenging but need to be confronted if we are to deal successfully with the increasing numbers of elderly and frail people in modern societies. To do this, we need to understand the mechanisms responsible for age-associated increased susceptibility to infections and immune-influenced chronic degenerative diseases of ageing. Defining relevant age-associated alterations and identifying reliable biomarkers for monitoring clinically-relevant immune status in the elderly population is crucial to overcoming these problems. Here, we briefly outline age-associated changes to immunity collectively termed ‘immunosenescence’.

1999 ◽  
Vol 58 (3) ◽  
pp. 685-695 ◽  
Author(s):  
Bruno Lesourd ◽  
Lynda Mazari

Immune function declines with age, leading to increased infection and cancer rates in aged individuals. In fact, recent progress in the study of immune ageing has introduced the idea that rather than a general decline in the functions of the immune system with age, immune ageing is mainly characterized by a progressive appearance of immune dysregulation throughout life. Changes appear earlier in life for cell-mediated immunity than for humoral immunity. Thus, agerelated modifications in cell-mediated immunity, i.e. changes in naive: memory T-cells, mature: immature T-cells, T-helper 1: T-helper 2 cells are more important in the elderly than changes in humoral immunity, i.e. CD5: CD5+ cells or length of antibody responses. Such evolution of the immune system has been linked to declining thymus function and to accumulative antigenic influence over the lifespan. In contrast, innate immunity (macrophage functions) is preserved or even increased during the ageing process. This finding shows that the ‘primitive’ immune system is less affected by the ageing process than the sophisticated specific immune system. The present review focuses on innate and cell-mediated immune changes with ageing. It provides evidence that primary changes (intrinsic modifications in the immune system) and secondary changes (resulting from environmental influences during the lifespan) exert different influences on the immune system. Primary changes, occurring in healthy individuals, seem less important nowadays than they were considered to be previously. For example, interleukin 2 secretion in some very healthy aged individuals is comparable with that in younger adults. Primary immune changes may not explain the increased incidence and severity of infections observed in the elderly population. Secondary immunological changes are far more frequent and are certainly responsible for most of the immune modifications observed in the elderly population. Environmental factors leading to secondary immune dysfunctions include not only antigenic influence, which is a reflection of diseases experienced over the lifespan, but also many other factors such as drug intake, physical activity and diet; factors for which important changes occur in the elderly population. Nutritional factors play a major role in the immune responses of aged individuals and the present review shows that nutritional influences on immune responses are of great consequence in aged individuals, even in the very healthy elderly.


2000 ◽  
Vol 78 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Helle Bruunsgaard ◽  
Bente Klarlund Pedersen

2020 ◽  
Vol 126 (4) ◽  
pp. 533-551 ◽  
Author(s):  
Haobo Li ◽  
Margaret H. Hastings ◽  
James Rhee ◽  
Lena E. Trager ◽  
Jason D. Roh ◽  
...  

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.


2015 ◽  
Vol 112 (10) ◽  
pp. E1143-E1151 ◽  
Author(s):  
Ann Thanawastien ◽  
Robert T. Cartee ◽  
Thomas J. Griffin ◽  
Kevin P. Killeen ◽  
John J. Mekalanos

Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell–independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a “carrier protein” antigen. Such “conjugate vaccines” efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines.


2006 ◽  
Vol 16 (2) ◽  
pp. 125-139 ◽  
Author(s):  
John J Ah-Chan ◽  
Susan Downes

Age has been identified as the single most impor-tant demographic predictor of blindness and visual impairment. Visual impairment is the second most prevalent physical disability in the elderly population. The prevalence of blindness and visual impairment after 60 years of age increases significantly. Furthermore, the number of older people with functional vision impairment is expected to double in the next decade. Visual impairment in the elderly population is commonly due either to localized ocular pathology (cataracts, glaucoma and age-related macular degeneration) or systemic disease with associated ocular or visual pathway involvement (hypertension, diabetes and cerebrovascular disease). Physicians involved in the care of older people play a crucial role in the recognition, prevention and management of morbidity related to visual impairment in this population. Timely screening, referral, intervention and visual rehabilitation is thought to be capable of reducing new blindness and visual impairment by at least one-third.


2015 ◽  
Vol 5;18 (5;9) ◽  
pp. E863-E876
Author(s):  
Giustino Varrassi

Background: Elderly patients in general exhibit a higher incidence of chronic and neuropathic pain conditions. This group poses a particular clinical challenge due to age-related pharmacokinetic and pharmacodynamic issues, comorbid conditions, and polypharmacy, as well as frailty and cognitive decline. Poor control of pain has consistently been identified as an issue for older people. The identification of safe and efficacious treatments for chronic pain remains a critical public health concern, especially considering the progressive increase of the world’s elderly population. Objectives: This narrative review deals with the principal alterations of the somatosensory system together with changes in non-neuronal cells in the course of aging. The possibility to control chronic pain based on an innovative strategy which addresses non-neuronal cell dysregulation control will also be discussed. Study Design: Narrative review. Results: Peripheral nerves display functional, structural, and biochemical changes with aging that mainly involve Aδ fibers. Alteration in the responses to heat pain in the middle insular cortex and primary somatosensory cortex are also observed in the elderly. In general, pain threshold increases with age while the threshold of pain tolerance remains unchanged or decreases. Additionally, other important modifications of the pain perception system in this age group consist in a clear reduction in the descending inhibitory capacity with an associated increase in central sensitization. Furthermore, different changes concern immune system cells, such as mast cells and microglia, that with age show an increase in their sensitivity to noxious stimuli and a decreased capability to be regulated by homeostatic endogenous systems. Since these cells are the primary interlocutors for pain neurons, their alterations lead to changes that promote persistent neuroinflammation, thereby impacting pain neuronal cell functionality. Limitation: This review is not an exhaustive review for the current evidence supporting the role of immune cells in influencing pain somatosensory neuron functions. It is also important to stress the small number of studies designed to determine the efficacy and safety of anti-pain therapies in elderly patients. Conclusion: Non-neuronal cells of immune system origin such as microglia and mast cells, along with astrocytes, are capable of influencing pain somatosensory neuron functions. These nervous system non-neuronal cells may thus be viewed as innovative targets for persistent pain control. Among therapies aiming at preserving the functionality of non-neuronal cells, palmitoylethanolamide, with its high efficacy/risk ratio, may be an excellent co-treatment for the ever-growing elderly population with chronic pain. Key words: Elderly, chronic and neuropathic pain, mast cells, glial cells, neuroinflammation, micronized and ultra-micronized palmitoylethanolamide


Author(s):  
Mara Caroline ◽  
Ryan Bradley ◽  
Mimi Guarneri

The older population is challenging to treat for numerous reasons, including comorbid conditions and increased susceptibility to adverse drug reactions, limiting medical therapy. They are at increased risk for loneliness and depression, which strongly impacts their cardiovascular outcomes, and they also have different values, usually prioritizing quality of life over mortality objectives. Finally, the elderly are underrepresented in cardiovascular clinical trials, thus limiting the applicability of guideline recommendations. This chapter emphasizes the importance of a comprehensive assessment of individual circumstances when assessing cardiovascular health in the elderly population. The chapter focuses on the role of nutrition, resiliency, and exercise for the prevention and treatment of cardiovascular disease. Nutrient deficiencies commonly seen with cardiovascular drugs are also discussed, as well as specific integrative strategies for optimizing dyslipidemia, atrial fibrillation, and heart failure in this population.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 751
Author(s):  
Eric C. Bredahl ◽  
Joan M. Eckerson ◽  
Steven M. Tracy ◽  
Thomas L. McDonald ◽  
Kristen M. Drescher

The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.


2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Juliana de Souza Apostólico ◽  
Victória Alves Santos Lunardelli ◽  
Fernanda Caroline Coirada ◽  
Silvia Beatriz Boscardin ◽  
Daniela Santoro Rosa

Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.


Toxics ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 18
Author(s):  
Arulkumar Nagappan ◽  
Su Bum Park ◽  
Su-Jun Lee ◽  
Yuseok Moon

Particulate matter (PM) is a major and the most harmful component of urban air pollution, which may adversely affect human health. PM exposure has been associated with several human diseases, notably respiratory and cardiovascular diseases. In particular, recent evidence suggests that exposure to biomass-derived PM associates with airway inflammation and can aggravate asthma and other allergic diseases. Defective or excess responsiveness in the immune system regulates distinct pathologies, such as infections, hypersensitivity, and malignancies. Therefore, PM-induced modulation of the immune system is crucial for understanding how it causes these diseases and highlighting key molecular mechanisms that can mitigate the underlying pathologies. Emerging evidence has revealed that immune responses to biomass-derived PM exposure are closely associated with the risk of diverse hypersensitivity disorders, including asthma, allergic rhinitis, atopic dermatitis, and allergen sensitization. Moreover, immunological alteration by PM accounts for increased susceptibility to infectious diseases, such as tuberculosis and coronavirus disease-2019 (COVID-19). Evidence-based understanding of the immunological effects of PM and the molecular machinery would provide novel insights into clinical interventions or prevention against acute and chronic environmental disorders induced by biomass-derived PM.


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