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When stem cells grow old: phenotypes and mechanisms of stem cell aging

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Schultz, Michael B., Sinclair, David A.·2016·Development

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Abstract

All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan.

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“Only when function was measured on a per-cell basis were old immunophenotypic HSCs shown to have a greatly reduced ability to engraft and properly differentiate in new hosts (Dykstra et al., 2011; Liang et al., 2005; Morrison et al., 1996).”
Background
Isolation of Adult Mouse Myogenic Progenitors
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Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging
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Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
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Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression
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Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog
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PGRP-SC2 Promotes Gut Immune Homeostasis to Limit Commensal Dysbiosis and Extend Lifespan
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Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle
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Inhibition of JAK-STAT signaling stimulates adult satellite cell function
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Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis
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Acetylated Lysine 56 on Histone H3 Drives Chromatin Assembly after Repair and Signals for the Completion of Repair
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Muscle transplantation between young and old rats: age of host determines recovery
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Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
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Fat Metabolism Links Germline Stem Cells and Longevity in C. elegans
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The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells.
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ROS Production and NF-κB Activation Triggered by RAC1 Facilitate WNT-Driven Intestinal Stem Cell Proliferation and Colorectal Cancer Initiation
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A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells
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The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion
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Short-term calorie restriction enhances skeletal muscle stem cell function
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Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation
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Redox Regulation by Keap1 and Nrf2 Controls Intestinal Stem Cell Proliferation in Drosophila
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Centrosome misorientation reduces stem cell division during ageing
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The longest telomeres: a general signature of adult stem cell compartments
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Lifespan Extension by Preserving Proliferative Homeostasis in Drosophila
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Germ-Cell Loss Extends C. elegans Life Span through Regulation of DAF-16 by kri-1 and Lipophilic-Hormone Signaling
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Age‐related differences in absolute numbers of skeletal muscle satellite cells
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A Population of Myogenic Stem Cells That Survives Skeletal Muscle Aging
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Direct Control of Germline Stem Cell Division and Cyst Growth by Neural Insulin in Drosophila
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Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation
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Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction
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Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
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“Senescent niche cells might also affect neighboring stem cells by secreting tumor-promoting mitogens and pro-inflammatory cytokines that negatively affect stem cell function through paracrine signaling (Coppé et al., 2008).”
Background
Mouse Strain-Dependent Changes in Frequency and Proliferation of Hematopoietic Stem Cells During Aging: Correlation Between Lifespan and Cycling Activity
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Glucose and Glutamine Metabolism Regulate Human Hematopoietic Stem Cell Lineage Specification
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Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment
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Decline in Self-Renewal Factors Contributes to Aging of the Stem Cell Niche in the Drosophila Testis
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Effects of Aging and Niche Microenvironment on Spermatogonial Stem Cell Self-Renewal
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Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death
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Relative roles of TGF‐β1 and Wnt in the systemic regulation and aging of satellite cell responses
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A review and appraisal of the DNA damage theory of ageing
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SIRT2 induces the checkpoint kinase BubR1 to increase lifespan
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Self-citation
Insulin levels control female germline stem cell maintenance via the niche in Drosophila
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Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones
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Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.
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Germline Energetics, Aging, and Female Infertility
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Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
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Epidermal stem cells are retained in vivo throughout skin aging
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Stem Cell Aging Is Controlled Both Intrinsically and Extrinsically in the Drosophila Ovary
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Neural Stem and Progenitor Cells Retain Their Potential for Proliferation and Differentiation into Functional Neurons Despite Lower Number in Aged Brain
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Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro
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Mild Hypoxia Enhances Proliferation and Multipotency of Human Neural Stem Cells
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Circulating Growth Differentiation Factor 11/8 Levels Decline With Age
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Immortal Strands? Give Me a Break
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Nfatc1 orchestrates aging in hair follicle stem cells
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Telomere Shortening in Neural Stem Cells Disrupts Neuronal Differentiation and Neuritogenesis
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Elimination of Unfit Cells Maintains Tissue Health and Prolongs Lifespan
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Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis
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Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles
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A pathway that links reproductive status to lifespan in Caenorhabditis elegans
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Dietary and Metabolic Control of Stem Cell Function in Physiology and Cancer
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Actin Dynamics Affect Mitochondrial Quality Control and Aging in Budding Yeast
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See all 331

Authors: Schultz, M. B., & Sinclair, D. A.
Venue: Development
Publisher: The Company of Biologists
Published: 2016-01-01
Volume: 143
Issue: 1
Pages: 3-14
ISSN: 0950-1991 (ISSN-L)
1477-9129
DOI: 10.1242/dev.130633
OpenAlex: W2286971754
Cited by: 331
References: 203
FWCI: 11.28
Type: journal article
Language: en
Open access: green

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When stem cells grow old: phenotypes and mechanisms of stem cell aging

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