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Literature Review | Study on Hair Growth in Aged Mice

Mice have long been indispensable partners in our research. However, as they age, their fur gradually thins, leading to extensive hair loss and even complete alopecia. Consequently, many researchers worry about the mice’s physiological health, fearing that this may compromise the experimental outcomes.

The authors, in the journal J Invest Dermatol, observed hair growth in aged mice and measured relevant biomarkers, finding that… Follistatin, Dkk1, and Sfrp4 It affects hair growth in aged mice, which helps us better understand the hair‑growth process in this population.

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I. Hair Follicle Growth Cycle

Hair follicle: Hair follicles are the fundamental units responsible for hair growth, and damage to them can impair hair development. Once a hair follicle undergoes necrosis, it cannot regenerate; therefore, from a scientific perspective, changes in and necrosis of hair follicles are the root causes of all types of hair loss.

Growth period: During the active growth phase, the hair follicle is at its deepest. Once the hair reaches its maximum length in the anagen phase, it remains at that length and ceases to grow.

Catagen phase: The cessation of mitotic activity in the hair matrix cells marks the onset of the catagen phase.

Telogen phase: After the catagen phase ends, clubbing of the nails develops, and the clubbed nails subsequently fall off.

 

Hair follicles cycle repeatedly through these three phases, and human hair generally shows little variation throughout the four seasons—this is because Each hair has its own distinct growth cycle, and hair shedding and regrowth are maintained in dynamic equilibrium; however, in mice, these processes occur synchronously. , which can be used to investigate changes in mouse hair growth and the factors that influence it.

 

II. Experiments and Conclusions

The authors of J Invest Dermatol first observed differences in hair growth between aged and young mice, then conducted transplantation experiments to determine whether the skin’s extrinsic environment influences hair growth, and finally examined at the molecular level the factors underlying these effects.

1. Take photographs to document the differences in hair growth between aged and young mice.

Experimental results: (see Figure 1)

Figure 1: Differences in hair growth between aged and young mice

 

Experimental conclusion:

(1) Compared with young mice, aged mice exhibit reduced hair growth length and rate, accompanied by an exceptionally prolonged telogen phase. This inability to re-enter the anagen phase is referred to as “telogen retention.”

(2) Two possible explanations for the observed phenomenon were proposed:

① Hair follicle stem cells malfunction and fail to respond to signaling cues.

② During the growth phase, activation signals fail to be properly transmitted to hair follicle stem cells.

 

Author: J Invest Dermatol Flow cytometry revealed that the number of hair follicle stem cells does not decline significantly during aging, though other changes cannot be ruled out. 。

 

2. The Influence of the Skin Environment on Hair Growth

Experimental method: (see Figure 2)

Figure 2: Experimental method for investigating the effects of the skin environment on hair growth

 

Experimental results: (See Figures 3 and 4)

Figure 3

Figure 4

 

For small donor skin grafts (5×3 mm), hair regrowth begins at the wound margins and can extend into the central area; in contrast, larger skin grafts (15×10 mm) support hair regrowth only at the wound edges, without affecting the central region, which remains in a “resting phase–retained” state.

 

Experimental conclusion:

The skin environment of young mice can promote hair regrowth in aged mice, though the extent of this effect is limited. Quantitative RT‑PCR analysis revealed that Bmp‑2 (bone morphogenetic protein‑2) levels were elevated in the skin of aged mice, whereas follistatin (Fst) levels were reduced. The environment can regulate the hair regeneration process through molecular signaling. 。

 

3. Follicle-stimulating hormone promotes hair growth in mice.

Follistatin inhibits the secretion of follicle-stimulating hormone, which in turn regulates human development, growth, pubertal sexual maturation, and a range of reproductive‑related physiological processes.

 

Experimental method:

Figure 5: Experimental method for examining the effect of follistatin on hair growth in mice

Experimental results:

Skin hair follicles implanted with follistatin beads rapidly entered the anagen phase, with hair regrowth, whereas the control group follicles that received no implantation remained in the telogen phase for a prolonged period.

 

Experimental conclusion:

Follistatin contributes to the promotion of hair follicle entry into the anagen phase, thereby enhancing hair growth.

4. Hair follicles are regulated by activation signals during the anagen phase, which are transmitted via the Wnt signaling pathway; antagonists of Wnt proteins can inhibit the normal function of this pathway. These antagonists fall into two major families: the SFRP proteins and the Dickkopf proteins. Our findings indicate that while Wnt ligands are normally expressed in aged mice, Wnt antagonists—namely Dkk1 and Sfrp4—are markedly upregulated. This suggests that the “quiescence retention” observed in aged mice is attributable to the inhibitory effects of these Wnt antagonists.

 

 

III. Conclusion

A series of experiments revealed that the thinning of hair in aged mice is attributable to their hair follicles being trapped in a prolonged “quiescent‑retained” state, preventing them from reentering the growth phase. Moreover, the skin microenvironment plays a critical role in hair growth; analysis showed that, in aged mice, follistatin levels are downregulated, while the Wnt pathway inhibitors Dkk1 and Sfrp4 are upregulated—factors that collectively contribute to this phenomenon.

 

 

References:

https://doi.org/10.1038/jid.2014.139

DOI: 10.1038/jid.2014.139

 

 

Aniphe BioLab can provide synchronized hair‑growth‑cycle mouse models and hairless mouse models. Please feel free to inquire!

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