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Immune ageing at single-cell resolution

Nature Reviews Immunology volume 22, pages 484–498 (2022)Cite this article

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Abstract

Ageing leads to profound alterations in the immune system and increases susceptibility to some chronic, infectious and autoimmune diseases. In recent years, widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system. These comprehensive approaches have expanded and detailed the current views of ageing and immunity. Here we review a body of recent studies that explored how the immune system ages using unbiased profiling techniques at single-cell resolution. 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. 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. We further discuss outstanding questions in the field and highlight techniques that will advance our understanding of immune ageing in the future.

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Fig. 1: Cellular and molecular components of inflammageing.
Fig. 2: Alterations of immune cell populations in ageing.
Fig. 3: Interactions between immune and senescent cells.

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Acknowledgements

The authors thank L. Arthur for editing the manuscript. The work was supported by a grant from the Aging Biology Foundation (to M.N.A.).

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  1. These authors contributed equally: Denis A. Mogilenko, Irina Shchukina.

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  1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA

    Denis A. Mogilenko, Irina Shchukina & Maxim N. Artyomov

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Immune ageing datasets: https://artyomovlab.wustl.edu/immune-aging/explore.html

Tabula Muris: https://tabula-muris.ds.czbiohub.org/

Tabula Muris Senis: https://tabula-muris-senis.ds.czbiohub.org/

Glossary

Multi-omics

An integrative analysis approach using datasets that broadly cover data generated from the genome, epigenome, transcriptome, proteome and metabolome.

Inflammageing

Chronic low-grade systemic inflammation occurring in the absence of a pathogen or exogenous inflammatory agent that develops with advanced age owing to endogenous pro-inflammatory processes.

Senescent cell

A terminally differentiated cell characterized by irreversible cell cycle arrest and a specific secretory profile that develops in response to various stress triggers and accumulates in aged organisms.

Caloric restriction

A dietary intervention that reduces average daily caloric intake below typical or habitual levels, while containing essential nutrients and not leading to malnutrition.

M1 macrophages

An historical, overly simplistic, classification of pro-inflammatory macrophages activated in vitro with interferon-γ (IFNγ) and lipopolysaccharide that only partially reflects the heterogeneity of highly specialized, dynamic and heterogeneous macrophage subsets in vivo, the activation of which is continuously shaped by multiple matrix and cellular signals in the tissue microenvironment.

T cell exhaustion

A specific state of T cell dysfunction driven by a persistent antigen stimulation and chiefly defined by reduced cytotoxicity and inability to produce pro-inflammatory cytokines (such as interferon-γ (IFNγ) and tumour necrosis factor (TNF)) and proliferate on T cell receptor stimulation.

Cellular indexing of transcriptomes and epitopes by sequencing

(CITE-seq). A method that uses oligonucleotide-labelled antibodies to integrate cellular protein and transcriptome measurements into an integrated single-cell readout.

Damage-associated molecular patterns

Endogenous molecules released from damaged or dying cells, such as mitochondria and chromatin components, which activate the innate immune system by interacting with pattern recognition receptors such as Toll-like receptors.

Spatial transcriptomics

Methods designed to map mRNA expression profiles in individual cells or groups of cells to their locations in histological tissue sections.

Imaging cytometry

Methods designed to combine flow cytometry or mass cytometry features with morphological analysis of thousands of cellular events in histological tissue sections.

Single-cell assay for transposase-accessible chromatin using sequencing

(scATAC-seq). A method for mapping the accessible genome of individual cells that allows epigenetic profiling with single-cell resolution.

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Mogilenko, D.A., Shchukina, I. & Artyomov, M.N. Immune ageing at single-cell resolution. Nat Rev Immunol 22, 484–498 (2022). https://doi.org/10.1038/s41577-021-00646-4

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