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Ageing and rejuvenation of tissue stem cells and their niches

Nature Reviews Molecular Cell Biology volume 24, pages 45–62 (2023)Cite this article

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Abstract

Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular mechanisms underlying ageing in the regenerative regions of different tissues as well as potential rejuvenation strategies. We focus primarily on brain, muscle and blood tissues, but also provide examples from other tissues, such as skin and intestine. We describe the complex interactions between different cell types, non-cell-autonomous mechanisms between ageing niches and stem cells, and the influence of systemic factors. We also compare different interventions for the rejuvenation of old regenerative regions. Future outlooks in the field of stem cell ageing are discussed, including strategies to counter ageing and age-dependent disease.

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Fig. 1: Organs with stem cells and stem cell niches.
Fig. 2: Changes in stem cells and their niches during ageing.
Fig. 3: Cell-autonomous and non-cell-autonomous mechanisms of stem cell ageing.

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Acknowledgements

The authors apologize for not including all relevant studies due to space constraints. They thank the reviewers for helpful comments. This work was supported by National Institutes of Health/National Institute on Aging P01AG036695 (A.B., M.A.G. and T.A.R.).

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Author notes

  1. Thomas A. Rando

    Present address: Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA, USA

Authors and Affiliations

  1. Department of Genetics, Stanford University, Stanford, CA, USA

    Anne Brunet

  2. Glenn Laboratories for the Biology of Ageing, Stanford University, Stanford, CA, USA

    Anne Brunet & Thomas A. Rando

  3. Molecular and Cellular Biology Department, Baylor College of Medicine, Houston, TX, USA

    Margaret A. Goodell

  4. Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA

    Margaret A. Goodell

  5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Thomas A. Rando

  6. Neurology Service, VA Palo Alto Health Care System, Palo Alto, CA, USA

    Thomas A. Rando

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The authors contributed equally to all aspects of the article.

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Glossary

Regenerative regions

Specific regions of the tissue that contain stem cells. In some tissues (for example, brain and intestine), these regions are well delineated. In other tissues (for example, muscle), stem cells are distributed throughout.

Neuroblasts

Progenitor cells that are committed to give rise to neurons.

Lymphoid cells

B lymphocytes, T lymphocytes and natural killer cells.

Myeloid lineage

Lineage giving rise to platelets, red blood cells, monocytes, neutrophils, basophils and eosinophils.

CD34

Sialomucin, a glycosylated transmembrane protein that is expressed by several stem cells, notably muscle stem cells and, in humans, haematopoietic stem cells.

Fibrogenic state

State characterized by abnormal deposition of extracellular matrix proteins and scarring of the tissue.

DNA methyltransferase 3A

(DNMT3A). Enzyme that adds methyl groups to cytosines in DNA.

Inflammatory cytokines

Signalling molecules secreted from immune cells or other cell types that promote inflammation.

Mechanosensitive cells

Cells that respond to mechanical stress or mechanical stimulation.

Bulge

Region of the outer root sheath of the hair which contains hair follicle stem cells.

Paracrine

Refers to the effect of factors in the vicinity of cells that secrete these factors.

ATM

Serine and threonine protein kinase that is recruited at and activated by double-strand breaks in DNA.

Extracellular vesicles

Lipid-bound vesicles, including exosomes, secreted into the extracellular space.

Nociceptive innervation

Innervation by sensory neurons that respond to damaging stimuli and send signals to the spinal cord and the brain.

ATR

Serine and threonine protein kinase that is activated by single-strand breaks in DNA.

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Brunet, A., Goodell, M.A. & Rando, T.A. Ageing and rejuvenation of tissue stem cells and their niches. Nat Rev Mol Cell Biol 24, 45–62 (2023). https://doi.org/10.1038/s41580-022-00510-w

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