During the past decade, unbiased single-cell-based applications of omics have been extensively developed. Mass cytometry, also known as cytometry by time of flight, is a variation of flow cytometry that relies on antibodies labelled with heavy metal ion tags, which allows the measurement of up to 40 individual epitopes in individual cells. Typically, flow cytometry experiments use fluorescently conjugated antibodies to detect surface and intracellular epitopes and/or fluorescent probes that measure cellular characteristics such as an abundance of DNA, mitochondria, lysosomes and lipid droplets. Flow cytometry is historically the first single-cell-based technique capable of simultaneously identifying 5вЂ“20 characteristics in individual cells. We focus our analysis on accumulating single-cell results obtained from mammalian model organisms and, where possible, we discuss how these findings can be translated to immune system ageing in humans (the datasets discussed are available to browse through an Artyomov laboratory webpage).ДЄ comprehensive assessment of a set of molecules, such as DNAs, RNAs, proteins and metabolites, is collectively termed вЂmulti-omicsвЂ™. In this Review, we summarize recent advances in our understanding of the ageing immune system and discuss how reported single-cell data and analyses align with existing concepts. Novel techniques, including single-cell RNA sequencing (scRNA-seq) (Box 2), have confirmed previous findings and expanded existing paradigms in ageing and immunity built on evidence from prior targeted studies. The current development of multi-omics and single-cell techniques 4 (Box 1) and progress in high-throughput biology and systems immunology 5 make it possible to comprehensively characterize cellular and functional heterogeneity and dynamic changes in the immune system during ageing. Interestingly, not all immune processes are uniformly sensitive to ageing, suggesting that various immune cell populations are heterogeneously impaired in older organisms (for example, в‰Ґ65 years in humans and в‰Ґ1.5 years in mice) 3. Together, these changes reshape physiological and immune landscapes as well as increase vulnerability to some diseases, frailty and multimorbidity 2. Loss of physiological integrity, disturbed tissue homeostasis and increasing deterioration of various biological systems, including the immune system, are among the key features of ageing 1.

We further discuss outstanding questions in the field and highlight techniques that will advance our understanding of immune ageing in the future.ДЄgeing is a multimodal process that occurs at several levels, with organs, tissues and cells undergoing substantial and simultaneous remodelling, thus limiting the power of conventional molecular biology approaches to resolve this complexity.

Focusing on the results obtained in mice and humans, we describe the multidimensional data that align with established concepts of immune ageing as well as novel insights emerging from these studies. Specifically, we discuss an emergent understanding of age-related alterations in innate and adaptive immune cell populations, antigen receptor repertoires and immune cell-supporting microenvironments of the peripheral tissues. Here we review a body of recent studies that explored how the immune system ages using unbiased profiling techniques at single-cell resolution. These comprehensive approaches have expanded and detailed the current views of ageing and immunity. In recent years, widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system. Ageing leads to profound alterations in the immune system and increases susceptibility to some chronic, infectious and autoimmune diseases.

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