Immunosenescence: Implications for response to infection and vaccination in older people

Highlights

• Immunosenescence affects both, innate and adaptive immunity.

• Immunosenescence limits the response to pathogens and vaccines.

• Lack of response to influenza vaccine results in increased morbidity and mortality.

• New studies are required to define effective vaccines for older populations.

Abstract

People aged 60 and older represent over 11% of the world population and it is expected to rise 22% by 2050. Population aging is associated to an increased frequency of age-related diseases including higher susceptibility to infections, cancer, cardiovascular and neurodegenerative diseases. Immunosenescence refers to the decline of the immune system associated to aging. It affects both, innate and adaptive immunity limiting the response to pathogens and to vaccines. The analyses of the immune system in elderly individuals determined several immune signatures constituting an immune risk phenotype that predicts mortality. An inverse CD4/CD8 ratio, loss of naïve T cells, increased numbers of terminally-differentiated T cells and oligoclonal expansions of virus-specific T cells constitute hallmarks of immunosenescence. Natural killer (NK) cells are also found severely altered in the elderly. The contribution of latent cytomegalovirus infection to immunosenescence of T and NK cells has been shown. Considering the worldwide ageing of the population in the next decades, the impact of infections will be a real health problem for older individuals requiring preventive strategies. Thus, further studies are required to analyse the bases of immunosenescence and to establish protocols to overcome the age-associated alterations of the immune response in order to define effective vaccines against those pathogens, such as influenza, contributing to increased morbidity and mortality in the elderly.

Introduction

The number of people worldwide aged over 60 years of age in 2013 was 841 million, four times higher than the 202 million that lived in 1950. However, this population will almost triple by 2050, when it is expected to surpass the two billion mark. Europe is currently the world's major area with the highest proportions of older persons and is projected to remain so for at least the next 50 years. About 37% of the European population is projected to be 60 or over in 2050, and almost 30% is projected to be 65 or over, doubling the percentages observed in 2000 [1]. This ageing of the population leads to an increase of the frequency of age-related diseases, like higher incidence of infections, cancer and neurodegenerative and cardiovascular diseases. Many of these conditions are related to the age-associated decline of the immune system, a process that is generally referred as “immunosenescence” [2], [3], [4]. However, immunosenescence not only describes the alterations produced by chronologic ageing, but also changes due to chronic activation of immune system associated to virus infections (human immunodeficiency virus, HIV; cytomegalovirus, CMV), inflammatory diseases, cancer or organ transplantation, a process termed “early” or “premature” immunosenescence) [5], [6].

The effect of age over immunity includes alterations in the distribution and function of cells involved in innate and adaptive immunity [7]. Innate and adaptive immunity are closely related and alterations in innate immunity may affect the priming of adaptive immunity and, at the same time, malfunction of aged CD4 T cells fails to sustain the responses of innate and adaptive immune cells against pathogens or cancerous cells.

In this review, we summarize our current knowledge on the molecular and cellular mechanisms involved in immunosenescence with an emphasis on describing those biomarkers associated to ageing and the relevance of latent CMV infection in immunosenescence and its consequences in sepsis and response to vaccination. We analyse the effect of gender on immunosenescence and how other age-associated diseases are also related to immunosenescence.