Background
In mammals, desynchronized circadian rhythm leads to various biological symptoms. In skin and hair, human epidermal stem cell function
in vitro
is regulated by circadian oscillations, and ...thus contributes to tissue aging when deregulated. In mice, circadian arrhythmia of hair follicle stem cells contributes to age-related hair follicle cycling defects. Despite the well-described impact of circadian oscillations through a feedback loop involving the clock pathway on hair and skin stem cell function
in vitro
, little is known about the change in characteristics or regenerative properties of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) after long-term alteration of circadian rhythm
in vivo
.
Objectives
The present study was designed to asses hHF, hEpi, and hHFDP precursors and stem cell properties in response to clock pathway alteration due to long-term deregulated circadian rhythm
in vivo
.
Materials & Methods
A clinical study protocol was designed to include two groups of women: diurnal workers (control) and shift workers (deregulated). After informed consent, two 3-mm fresh punch biopsies were taken from the occipital region of each donor (10 donors/group). Cell culture characterization, measurement of colony area, culture medium analysis, and RT-qPCR analysis were carried out.
Results
Long-term circadian rhythm deregulation affected clock pathway protein expression and correlated with alterations in hHF, hEpi, and hHFDP properties.
Conclusions
This study provides, for the first time in humans, evidence that
in vivo
deregulation of the clock pathway affects regenerative properties of human skin and hair precursor cells.
The decline of tissue regenerative potential of skin and hair is a hallmark of physiological ageing and may be associated with age‐related changes in tissue‐specific stem cells and/or their ...environment. Human hair follicles (hHF) contain keratinocytes having the property of stem cells such as clonogenic potential. Growth capacity of hHF keratinocytes shows that most of the colony‐forming cells are classified as holoclones, meroclones or paraclones when analysed in a clonal assay (Cell, Volume 76, page 1063). Despite the well‐known impact of ageing on human hair growth, little is known about changes in hHF keratinocyte clonogenic potential with age. This study aimed at assessing the clone‐forming efficiency (CFE) of hHF keratinocytes from three age groups of human donors. It demonstrates that ageing affects hHF keratinocyte CFE.
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•Age-associated thin hairs exhibit imbalanced hair keratins and KAPs expressions and changes in cortex organization.•In hair thinning, hair shape correlates with diameter with thin ...hairs having a round shape.•Thin hairs have a reduced frequency of medullae and a reduced number of cuticle layers.•Thin hairs exhibit an increased rigidity, a decrease of the viscosity and a decrease of the water diffusion coefficient.
Hair thinning occurs during normal chronological aging in women and in men leading to an increased level of thinner hair shafts alongside original thicker shafts. However, the characteristics of age-associated thin hairs remain largely unknown. Here we analyzed these characteristics by comparing at multiscale thin and thick hairs originated from Caucasian women older than 50 years. We observed that the cortex of thick hair contains many K35(+)/K38(−) keratinocytes that decrease in number with decreasing hair diameter. Accordingly, X-ray diffraction revealed differences supporting that thin and thick hairs are different with regards to the nature of the intermediate filaments making up their cortices. In addition, we observed a direct correlation between hair ellipticity and diameter with thin hairs having an unexpected round shape compared to the elliptic shape of thick hairs. We also observed fewer cuticle layers and a reduced frequency of a medullae in thin hairs. Regarding mechanical properties, thin hairs exhibited a surprising increased rigidity, a decrease of the viscosity and a decrease of the water diffusion coefficient. Hence, aged-associated thin hairs exhibit numerous modifications likely due to changes of hair differentiation program as evidenced by the modulations in the expression of hair keratins and keratin-associated proteins and by the X-ray diffraction specters. Hence, hair thinning with age does not consist simply of the production of a smaller hair. It is rather a more profound process likely relying on the implementation of an “aged hair program” that takes place within the hair follicle.
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