Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process

Ortega‐Martínez, Marta; Rodríguez-Flores, Laura E.; Ancer-Arellano, Adriana; Cerda‐Flores, Ricardo M.; de-la-Garza-González, Carlos; Áncer‐Rodríguez, Jesús; Jaramillo‐Rangel, Gilberto

doi:10.1007/s00408-016-9890-3

Cited by 21 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4a,b,d). The reduced club cell proliferation rate that we observed was in agreement with a previous study which found that the percentage of PCNA + proliferating cells fell by 69% between 2 and 24 months of age 43 . Notably, the baseline level of PCNA + cells in young mice in this study was 0.068%, whereas our baseline level of EdU incorporation over 2 weeks in club cells in young mice was 17.7%.…”

Section: Discussionsupporting

confidence: 93%

Distal lung epithelial progenitor cell function declines with age

Watson

Sanders

Dunmore

et al. 2020

Sci Rep

View full text Add to dashboard Cite

tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3-and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their crosssectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases. Tissue stem cell exhaustion is a key hallmark of aging 1 , but has not been fully investigated in the lung. It is important to characterise how lung stem cell dynamics change with aging, and how they contribute to age-related loss of pulmonary function. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung cancer typically onset in old age, and it is thought that aging contributes to their pathogenesis. A detailed understanding of the changes that occur in healthy aging will provide a baseline for understanding the further changes that occur during the development of common age-related pulmonary diseases. Healthy lung aging is characterised by complex multiscale changes in the physical structure of tissue and in its cellular and molecular composition. There is a stiffening of the chest wall, a decrease in respiratory system resistance, and an increase in dynamic compliance and hysteresis 2-5. Lung tissue typically becomes less able to regenerate with aging. This has been described in well-defined animal models where there is an absence of the confounding variables typically found in the human population. For example, in mice, there is a progressive loss in regenerative capacity in response to insults such as pneumonectomy, influenza, or E. coli lipopolysaccharide 6-11. Specific changes in defined progenitor cell populations likely underlie the changes in structure and function of the lung. Previous work showed that in the aging mouse upper airways, the number of basal epithelial progenitor cells is decreased, and that this is accompanied by a reduction in overall epithelial cell density. Additionally, gland-like structures bud off from the surface epithelium 12,13. In the distal lung, t...

show abstract

Section: Discussionsupporting

confidence: 93%

Distal lung epithelial progenitor cell function declines with age

Watson

Sanders

Dunmore

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These results are consistent with the reduced ciliary beat frequency that was observed in aged versus young mice [ 131 ]. Old mice also have a reduced number of epithelial cells due to increased apoptosis, and resulting in epithelial thinning [ 132 ]. Virus-induced damage of club cells and their subsequent regeneration was similar in young and aged mice, however [ 133 ].…”

Section: Age-associated Changes In Pulmonary Structure and (Immunementioning

confidence: 99%

The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma

Bullone

Lavoie

2017

IJMS

View full text Add to dashboard Cite

Aging is associated with a dysregulation of the immune system, leading to a general pro-inflammatory state of the organism, a process that has been named inflamm-aging. Oxidative stress has an important role in aging and in the regulation of immune responses, probably playing a role in the development of age-related diseases. The respiratory system function physiologically declines with the advancement of age. In elderly asthmatic patients, this may contribute to disease expression. In this review, we will focus on age-related changes affecting the immune system and in respiratory structure and function that could contribute to asthma occurrence, and/or clinical presentation in the elderly. Also, naturally occurring equine asthma will be discussed as a possible model for studying the importance of oxidative stress and immun-aging/inflamm-aging in humans.

show abstract

“…The lower respiratory tract includes the trachea and within the lungs, the bronchi, bronchioles, and alveoli. This system performs or participates in several functions: air conduction, gas exchange, olfaction, and phonation [13][14][15].…”

Section: Pulmonary Cartilagementioning

confidence: 99%

“…On the opposite, other authors affirm that PCNA is the most reliable and versatile of all markers used to analyze cell proliferation [75]. In the past, we have successfully used the immunohistochemical detection of PCNA in studies of cell turnover in lung [76].…”

Section: Identification and Measurement Of Cell Proliferationmentioning

confidence: 99%

Chondrocyte Turnover in Lung Cartilage

Gopar-Cuevas¹,

Niderhauser‐García²,

Arellano³

et al. 2018

Cartilage Repair and Regeneration

Self Cite

View full text Add to dashboard Cite

Cartilage is a highly differentiated connective tissue that forms mechanical support to soft tissues and is important for bone development from fetal period to puberty. It is conformed by chondrocytes and extracellular matrix. It is generally believed that adult cartilage has no capacity to renewal. A delicate balance between cell proliferation and cell death ensures the maintenance of normal tissue morphology and function. Stem cells play essential roles in this process. Mesenchymal stem cells (MSCs) can give rise to multiple lineages including bone, adipose and cartilage. Nestin protein was initially identified as a marker for neural stem cells, but its expression has also been detected in many types of cells, including MSCs. In vivo, chondrocyte turnover has been almost exclusively studied in articular cartilage. In this chapter we will review the findings about the chondrocyte turnover in lung cartilage. We have presented evidence that there exist nestinpositive MSCs in healthy adulthood that participates in the turnover of lung cartilage and in lung airway epithelium renewal. These findings may improve our knowledge about the biology of the cartilage and of the stem cells, and could provide new cell candidates for cartilage tissue engineering and for therapy for devastating pulmonary diseases.

show abstract

Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process

Cited by 21 publications

References 34 publications

Distal lung epithelial progenitor cell function declines with age

Distal lung epithelial progenitor cell function declines with age

The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma

Chondrocyte Turnover in Lung Cartilage

Contact Info

Product

Resources

About