TELOMERASE, THE KEY TO DELAYING CELL AGING
Aging is a natural, gradual and continuous process in time induced by intrinsic
and extrinsic factors that modify the properties and performance of materials.
The general definition can be applied to all kinds of materials, including physical,
chemical, biological or cellular material.
Living beings, as all materials, are subject to a continuous and gradual aging
process that results in a modification of their properties, functions or structure.
The elements responsible for biological aging are both extrinsic and intrinsic.
Extrinsic agents include exposure to toxins (tobacco, alcohol, drugs, etc.), UV
radiation (photoaging), stress, nutrition, and others. This automatically leads to
the belief that people who are repeatedly exposed to extrinsic factors such as
those mentioned above will age before those not exposed to them.
Aside from extrinsic agents, which in many cases can be avoided, there are
unavoidable intrinsic agents resulting from life itself.
One of the most widely accepted theories, albeit not the only one, is the free
radicals theory. In their normal functioning, cells generate free radicals, reactive
oxygen species (ROS), which are highly reactive compounds that change the
structure of macromolecules (nucleic acids, proteins, lipids) in the organism,
leading to the loss of their function and therefore alterations in cellular, tissue
and organ function. Our organism is in a constant state of wear and repair, and
aging begins with an imbalance in this wear-repair state such that the
accumulated damage is greater than the regenerative capacity.
The appearance of the skin is conditioned by fibroblasts, the most numerous
cells in connective tissue, the function of which is the synthesis and maintenance
of the extracellular matrix. These are essential for maintaining the skin's
firmness, elasticity and regenerative capacity, but over the years aged fibroblasts
eventually predominate over young ones, and the skin loses its functional
characteristics. Skin aging has numerous symptoms, typically including reduced
hydration, the appearance of thin and deep creases and subsequently wrinkles,
loss of firmness and elasticity, and finally senile elastosis.
In addition, the renewal rate of epidermal cells falls, reducing skin thickness,
and sebaceous glands atrophy, reducing sebum secretion, which reduces the
feeling of skin comfort.
The damage caused by internal and external factors is gradual and cumulative,
and results in the onset of the deterioration associated with aged skin.
Cells reduce their metabolic and replicative capacity over time as a result of their
morphological and biochemical changes. This affects their function and reduces
their number of duplications. This loss of replicative capacity is known as
replicative or cellular senescence. The existence of a molecular clock has been
suggested, marking the moment at which the cell's replicative capacity ends and
the cell becomes senescent.
Elizabeth Blackburn, Carol Greider and Jack Szostak were awarded the 2009
Nobel Prize in Medicine for their work relating telomeres to chromosomal
protection and cellular aging, as well as for the discovery of telomerase, an
enzyme that protects telomeres.
Telomeres (from the Greek telos, "end" and meros, "part") are the end parts of
chromosomes and consist of highly repetitive, non-coding DNA regions, with
the main function of providing structural stability to chromosomes in eukaryotic
cells, cell division and the lifetime of cell lines. (Fig. 1)
Fig 1. Image of a chromosome (left) and a telomere (right)
As a eukaryotic cell carries out the cellular division process, mitosis, it loses
fragments of telomeres due to the non-replication of the ends of the linear DNA
sequences, causing their shortening and leading to a gradual decrease in the
functionality of the cell and ultimately to its death. At the same time, the
extrinsic and intrinsic factors involved in aging contribute to shortening the
telomeres.
Telomeres of differentiated cells will be shorter in cells that have divided more
times than in younger cells. In addition, cells of older organisms divide fewer
times than cells of younger organisms.
Several experimental studies have shown that the gradual shortening of the
telomeres in the division process of adult cells leads to lower rates of cell
proliferation and triggers the senescence process. During cell division in stage
S, in which the DNA of the mother cell is replicated for a correct and equitable
transmission of the genetic information to the daughter cells, from 50 to 200
base pairs of the telomere DNA are not replicated. For this reason, telomeres are
shortened in each cellular cycle, limiting the number of divisions and thereby
the lifetime of the cell.
Telomerase is a ribonucleoprotein that is meant to add the DNA fragments lost
by the telomere in each cell division, preventing it from shortening, so that the
length of the telomere remains stable throughout the lifetime of certain types of
cell.
Telomerase activity is the main mechanism that protects telomere length in each
cell division, thereby increasing the number of divisions of the cells. Telomerase
is an enzyme that annuls cellular aging and death.
Telomerase is expressed in all types of cells during embryonic development, and
after the formation and development of the embryo it is restricted to certain cell
lines, such as adult stem cells and germ cells, and is repressed in all other
somatic cells, so that most cells in our organism have a limited life span.
It has been shown that the number of cellular duplications of fibroblasts depends
on age. Fetal fibroblasts can duplicate an average of 50 times before they enter
senescence, while after the age of 30 the number of duplications falls by 10 %
each decade, entering senescence when the cells lose their reproductive
capacity. (Fig. 2)
60
50
40
30
Número
duplicaciones
20
10
0
0
20
40
60
80
Years
Fig. 2. Number of duplications of fibroblasts as a function of age
The number of substances that induce the expression of telomerase in cells is
one of the aims of research on delaying aging, in order to find the 'pill of eternal
youth'.
In the area of cosmetic research, studies focus on finding compounds that
increase the duplication rate of fibroblasts in vitro, relating them to in vivo trials
that evaluate the structural properties of skin in an objective manner, such as
firmness, elasticity or cutaneous micro-relief.
Studies conducted with a purified fraction, Baicalin, of the extract of roots of the
plant Scutellaria baicalensis (which is widely used in traditional Chinese medicine
where it is known as Haung-qin) reveal that it induces the cellular expression of
telomerase in human fibroblast cultures, delaying the onset of senescence as it
increases the number of duplications by five, that is, 10% more than the 50
duplications performed on average by fibroblasts before entering senescence.
(Fig.3)
% accumulated divisions
25
20
15
Scutellaria baicalensis
10
Control
5
0
0
20
40
60
80
100
Days
Fig. 3. Increase in number of divisions of fibroblasts, expressed as a %.
In addition, in vitro results have been corroborated by in vivo studies, as after
continuous application on the skin for 56 days of the purified fraction, Baicalin,
of the extract of Scutellaria baicalensis in a concentration of 1.5% as a cosmetic
formulation, compared to the same cosmetic formulation without the extract, it
was observed that cutaneous micro-relief improved by 13%, firmness improved
by 12.5% and elasticity improved by 12.4%. These improvements can be
attributed to the delayed senescence of the fibroblasts.
Time passes inevitably, and it is impossible to delay chronological aging. But is
it possible to delay biological aging?
In light of current knowledge, telomerase is a key to delaying biological aging,
or at least to mitigating its effects.
José Pardo
Industrial Property and Documentation Dept.
Laboratorios ATACHE
TBI is the Exclusive Distributor for Atache in the United States