Gerontobiology of the Hair Follicle
From the biology of aging to the modern understanding of the hair follicle
Introduction
Dear friends,
The International Symposium on Anti-Aging Medicine held in November 2014 was a promising start to the Trichology Institute's collaboration with the company Estet. At the symposium, Yulia Ovcharenko presented a paper on hair aging.
The relevance and depth of the subject were reason enough to continue the conversation in the pages of Les Nouvelles Esthetiques Ukraine.
Today we begin a series of articles on hair aging, and we suggest starting at the very beginning, with the gerontobiology of the hair follicle.
Before we talk about gray hair, thinning or age-related alopecia, we need to understand what exactly is aging.
A hair is not simply a structure we see above the surface of the skin. Its life cycle is governed by a complex mini-organ, the hair follicle, where different cell types, signaling systems, the surrounding blood vessels, connective tissue and stem cells interact constantly.
It is the follicle's capacity for continuous regeneration that makes it such an interesting object for studying the aging process.
What is hair follicle aging?
Throughout life, the hair follicle is not in a constant state of growth. It goes through repeating cycles:
anagen → catagen → telogen → new anagen.
During anagen the hair grows actively. Catagen is the regression phase, followed by a resting period, telogen. Then the follicle is reactivated and starts the next cycle.
This regenerative capacity is preserved for many years thanks to the follicle's population of stem cells.
With age, however, the system gradually changes.
Hairs become thinner, their growth rate may slow, the length of the cycle phases changes, hair density decreases and pigmentation is disrupted.
Current research shows that these changes cannot be explained by a single factor. Follicle aging results from the interplay of changes inside the cells and changes in their surrounding microenvironment, the so-called stem-cell niche.
The hair follicle as a mini-organ
One of the important advances of modern hair biology is a change in how we think of the follicle itself.
The follicle is not just a "pouch" from which a hair grows.
It is a dynamic mini-organ in which the following interact:
- epithelial cells;
- dermal papilla cells;
- stem cells;
- melanocytes and melanocyte stem cells;
- connective tissue cells;
- vascular structures;
- immune cells;
- the extracellular matrix;
- signaling molecules.
The follicle's work is governed by a constant exchange of signals between these components.
That is why its aging cannot be seen as simple wear and tear on one group of cells.
Today, more and more evidence suggests that age-related changes affect the whole system of interactions inside and around the follicle.
Stem cells: the source of regeneration
Hair follicle stem cells (HFSCs) are of particular importance.
They are preserved in specific regions of the follicle and are activated when it moves into a new growth cycle.
In a young follicle this mechanism works very efficiently: the cells receive the necessary signals, activate, divide and form a new hair.
With age, the regenerative capacity of the system declines.
But there is an important nuance.
Aging does not necessarily mean that all stem cells simply disappear.
Research shows that some stem cells may persist but change their behavior, lose the ability to activate normally, or gradually become depleted. Changes in the surrounding niche play an important role here.
So the question of modern research is no longer only:
"How many stem cells are left?"
but rather:
"Why do the remaining cells stop working the way they used to?"
The stem-cell niche
A stem cell does not exist in isolation.
Its behavior is determined by its environment: cells, the extracellular matrix, blood vessels, nerve structures, immune cells, mechanical signals and various molecular factors.
This surrounding system is called the stem-cell niche.
It changes with age too.
The structure of the extracellular matrix, the mechanical properties of the tissue, cell-to-cell communication and the levels of various signaling molecules may all change.
As a result, the delicate balance between a stem cell's quiescence and its activation is disrupted.
This is why modern hair gerontobiology increasingly treats follicle aging as a problem not only of the cell itself, but of its surroundings.
COL17A1: one of the key mechanisms discovered after 2015
One of the best-known studies to change our view of how follicles age was published in Science in 2016.
The researchers showed a link between DNA damage in follicle stem cells, the breakdown of the protein COL17A1 (collagen XVII) and the subsequent loss of stem-cell properties.
COL17A1 helps to maintain hair follicle stem cells.
As damage accumulates, processes are triggered that lead to the breakdown of COL17A1. Aging stem cells gradually lose their "stemness" and switch to epidermal differentiation.
The result is a progressive loss of stem cells, miniaturization of the follicle and, in experimental models, gradual hair loss.
The study mattered because it showed that follicle aging is not simply a gradual slowing down. It is an active biological process.
Why does the follicle get smaller?
Follicle miniaturization is one of the most visible signs of age-related change.
With age, the size and architecture of individual follicle structures may change, including the bulge region and the dermal papilla.
At the same time, the interaction between epithelial and mesenchymal components changes.
Current reviews describe age-related transformation as a gradual structural and functional change of the entire follicular complex.
This matters especially for understanding the clinical picture.
When we see a finer hair, reduced density or slower growth, it may be the end result of a whole chain of changes that began much earlier.
Aging and pigmentation
Hair aging shows up not only as fewer or thinner hairs.
Another well-known sign is graying.
Hair pigmentation depends on melanocytes, and their maintenance is tied to a separate population of melanocyte stem cells.
This system also changes with age.
So gray hair and thinning, although often seen as a single sign of age, are different biological processes.
Current research treats the loss of pigment as the result of a disrupted melanocyte system in the follicle, while the decrease in hair density and thickness is linked mainly to changes in the follicle's own regenerative system.
Oxidative stress and aging
The hair follicle is a metabolically active structure.
In the aging process, oxidative stress, damage to cellular structures and impaired repair mechanisms become more important.
At the same time, it is important to avoid an oversimplified scheme of "free radicals = hair loss".
Oxidative stress is only one component of a far more complex system.
It can affect follicle cells, the state of their microenvironment, signaling pathways and the tissue's ability to sustain normal regeneration.
That is why modern gerontobiology considers oxidative stress alongside other mechanisms of aging: DNA damage, cellular senescence, metabolic changes and impaired cell-to-cell communication.
Does only the follicle age?
No.
This is perhaps one of the main conclusions science has reached over the past decade.
It is not only the follicle itself that ages.
The system that allows it to function ages.
The structure of the tissue changes.
The extracellular matrix changes.
Cell communication changes.
The work of stem cells changes.
The pigment system changes.
The vascular and immune environment changes.
It is the sum of these changes that we perceive clinically as hair aging.
What has changed in our understanding since 2015?
In 2015 we already knew that age-related changes in hair were tied to changes in the structure and function of the follicle, in pigmentation, in the hair shaft and in the surrounding tissues.
Over the following decade, the research picture has become far more complex.
Today the hair follicle is seen as a dynamic regenerative system with stem cells and their niche at its center.
Research in recent years describes in ever greater detail the interactions between stem cells, the dermal papilla, the extracellular matrix, immune cells and other cellular components. Single-cell RNA sequencing and other high-resolution technologies make it possible to study individual cell populations and changes in their molecular profiles with much greater precision than was possible in 2015.
And this work continues.
Can the hair follicle be rejuvenated?
This is one of the most interesting questions in modern trichology.
Researchers are already studying various approaches aimed at restoring stem-cell activity, changing their microenvironment, acting on signaling pathways and restoring the follicle's regenerative capacity.
Here, however, it is especially important to separate experimental biology from clinical practice.
Today, an interesting mechanism in a laboratory model does not yet mean there is a proven method of rejuvenating the human hair follicle.
Current reviews state directly that effective strategies for reversing age-related changes in the follicle remain an area of active research.
That is why it matters today to understand the difference between a promising line of research and a proven therapeutic method.
From gerontobiology to clinical trichology
The study of hair follicle aging matters far beyond academic science.
Understanding the mechanisms of aging helps us explain changes in hair better, tell physiological age-related processes from disease, and look for new directions in prevention and therapy.
But age on its own is not a diagnosis.
Thinning, changes in density, hair loss or premature graying can have different causes, including genetic, hormonal, inflammatory, metabolic and other factors.
That is why modern trichology begins not with an attempt to "stop aging", but with determining which process is actually taking place in a particular patient.
2015 → 2026: what we have learned
When this article first appeared in 2015, the gerontobiology of the hair follicle was already a fast-developing field of research.
Over the years since, we have gained a more detailed picture of:
- Stem cells: their behavior, depletion and ability to sustain regeneration.
- COL17A1: a molecular mechanism linked to the maintenance of stem cells and age-related follicle miniaturization.
- The follicle niche: the surrounding system that determines whether stem cells can do their job.
- The pigment system: the mechanisms behind the loss of melanocyte stem cells and graying.
- Cell communication: the complex network of signals between the different components of the follicle.
- Regenerative medicine: potential ways to restore the function of an aging follicle.
But the more we learn, the clearer one thing becomes:
hair aging is not a single process.
It is the result of many biological mechanisms interacting, gradually changing the follicle's ability to maintain its structure, its growth cycle and its function.
That is why the study of hair aging goes on.
And that is why the questions asked more than ten years ago have now reached a completely new level of detail.
Afterword
This publication begins with the text and the scientific context of 2015.
Today, more than ten years later, we return to the same topic with a much deeper understanding of hair follicle biology.
Science has not given a simple answer to the question of how to stop hair aging.
It has given something more important: an understanding of what exactly is happening inside the follicle, and why.
And that understanding is becoming the foundation for the next generation of research in trichology.
From understanding aging to understanding regeneration.
Sources for the scientific update
- Jang H. et al. Aging of hair follicle stem cells and their niches. BMB Reports. 2023.
- Matsumura H. et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016;351(6273).
- Organ Function is Preserved despite Reorganization of Niche Architecture in the Hair Follicle. Cell Stem Cell. 2023.
- Aging of hair follicle stem cells and their niche: mechanisms and regenerative therapeutic strategies. 2026.
Original publication: Ovcharenko Yu. S. Gerontobiology of the hair follicle. Les Nouvelles Esthetiques Ukraine. 2015; No. 1 (89): 76–81.