MCL-1 Protein – The "Guardian" of Hair Follicle Stem Cells and a New Therapeutic Target for Hair Loss

We may often hear about "hair loss due to staying up late" and "seasonal hair loss", but why is it sometimes difficult for hair to grow back once it falls out? Is it an issue of age or a physical cause? Recently, a study published in the journal Nature Communications identified a "key player behind the scenes" — the MCL-1 protein. Research has shown that MCL-1 protein is crucial for hair regeneration, opening up new possibilities for combating hair loss.

Why Can Hair "Grow Back in Cycles"? MCL-1 is the Key

The hair follicle cycle consists of the growth phase (anagen), regression phase (catagen), and resting phase (telogen). Hair follicle stem cells (HFSCs) are awakened during the telogen phase to drive new hair growth.

Hair can grow continuously because stem cells within the hair follicles are periodically awakened to enter the growth phase. These stem cells are like seeds, once activated, they gradually sprout and form new hair.

However, the problem is that this process is quite "risky" for the cells. Just as seeds must adapt to temperature and humidity before breaking through the soil, once hair follicle stem cells are activated, if they fail to stably "take root and sprout", they are prone to die.

Research shows that MCL-1 acts as a gatekeeper, protecting these "newly awakened" stem cells from being eliminated. Without it, once cells become active, they are subjected to various stresses and threats, leading them towards death. This also explains why even though we have hair follicles and stem cells, the process of regrowth after hair loss is sometimes difficult to initiate.

When stem cells awaken and begin preparing for work, they undergo a certain degree of "stress" response. At this point, if there is a lack of protective mechanisms, stress will accumulate, inducing a cellular mechanism called P53 to activate — it is the "safety officer" inside the cell, and once abnormalities are detected, it will trigger "self destruction".

In this study, MCL-1 is the one that prevents P53 from acting rashly. Without MCL-1, P53 would "press the delete button" more quickly, causing the stem cells that should regenerate to undergo apoptosis (programmed cell death) directly.

Further research discovered that another protein named Bak also plays a key role. It is an executor that promotes cell death, and MCL-1 normally inhibits its activity. That is to say, without MCL-1, Bak would also emerge to eliminate the stem cells, further accelerating the hair loss process.

Prospects & Challenges

Based on existing research data, the enormous potential of MCL-1 in application is revealed, but it cannot be ignored that MCL-1 is a key player in the cell's "survival pathway", which also means its activity needs to be precisely regulated. Once over activated, it may conversely lead to excessive cell proliferation and even cause problems like cancer.

Firstly, there is a safety issue. MCL-1 is an anti-apoptotic protein, and its overexpression may increase the risk of cancer. The boundary between balancing cell survival and inhibiting abnormal proliferation needs to be carefully considered.

Secondly, its targeting efficiency and specificity must be considered. Accurately regulating MCL-1 and Bak in different tissues to avoid affecting other cells requires highly targeted technology.

It is worth mentioning that the current research results are derived from animal experiments and mouse models. However, since the mechanism of hair follicle stem cells is highly conserved in humans, future validation of efficacy and risks in human models is still needed.

Therefore, MCL-1, this "guardian deity", may also become a "hidden danger"  in different scenarios. So, to apply it in hair loss treatment, several questions must still be considered: How to activate it only in hair follicles without affecting other tissues? How to avoid its long-term overexpression? Is it applicable to different types of hair loss?

This also means that there is long exploratory road from research to clinical application.

Summary

This study provides us with a new perspective on hair loss: not all hair follicle problems stem from a lack of stem cells, but rather from premature clearance of stem cells. And MCL-1 is the guardian preventing their disappearance.

The research not only solves the puzzle of why "hair doesn't grow back after falling out", but also opened a window for development of more precise and safer hair regrowth therapies in the future. If past hair loss research focused on making the scalp healthier, then this study is more like holding the bottom line for cell survival.