
A telomere (; ) is a region of repetitive
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
sequences associated with specialized proteins at the ends of linear
chromosome
A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
s (see
Sequences
In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is call ...
). Telomeres are a widespread genetic feature most commonly found in
eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s. In most, if not all species possessing them, they protect the terminal regions of
chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing
DNA repair
DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...
systems from mistaking the very ends of the DNA strand for a
double-strand break
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
.
Discovery
The existence of a special structure at the ends of chromosomes was independently proposed in 1938 by
Hermann Joseph Muller
Hermann Joseph Muller (December 21, 1890 – April 5, 1967) was an American geneticist who was awarded the 1946 Nobel Prize in Physiology or Medicine, "for the discovery that mutations can be induced by X-rays". Muller warned of long-term dang ...
, studying the fruit fly ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'', and in 1939 by
Barbara McClintock
Barbara McClintock (June 16, 1902 – September 2, 1992) was an American scientist and cytogenetics, cytogeneticist who was awarded the 1983 Nobel Prize in Physiology or Medicine. McClintock received her PhD in botany from Cornell University ...
, working with maize. Muller observed that the ends of irradiated fruit fly chromosomes did not present alterations such as deletions or inversions. He hypothesized the presence of a protective cap, which he coined "telomeres", from the Greek ''telos'' (end) and ''meros'' (part).
In the early 1970s, Soviet theorist
Alexey Olovnikov
Alexey Matveyevich Olovnikov (; 10 October 1936 – 6 December 2022) was a Russian biologist. Among other things, in 1971, he was the first to recognize the problem of telomere shortening, to predict the existence of telomerase, and to suggest the ...
first recognized that chromosomes could not completely replicate their ends; this is known as the "end replication problem". Building on this, and accommodating
Leonard Hayflick
Leonard Hayflick (May 20, 1928 – August 1, 2024) was an American anatomist who was Professor of Anatomy at the UCSF School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. He was also past pr ...
's idea of limited
somatic cell
In cellular biology, a somatic cell (), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Somatic cells compose the body of an organism ...
division, Olovnikov suggested that DNA sequences are lost every time a cell replicates until the loss reaches a critical level, at which point cell division ends. According to his theory of marginotomy, DNA sequences at the ends of telomeres are represented by tandem repeats, which create a buffer that determines the number of divisions that a certain cell clone can undergo. Furthermore, it was predicted that a specialized DNA polymerase (originally called a tandem-DNA-polymerase) could extend telomeres in immortal tissues such as germ line, cancer cells and stem cells. It also followed from this hypothesis that organisms with circular genome, such as bacteria, do not have the end replication problem and therefore do not age.
Olovnikov suggested that in germline cells, cells of vegetatively propagated organisms, and immortal cell populations such as most cancer cell lines, an enzyme might be activated to prevent the shortening of DNA termini with each cell division.
In 1975–1977,
Elizabeth Blackburn
Elizabeth Helen Blackburn (born 26 November 1948) is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the ...
, working as a postdoctoral fellow at
Yale University
Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
with
Joseph G. Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.
Blackburn,
Carol Greider
Carolyn Widney Greider (born April 15, 1961) is an American molecular biologist and Nobel laureate. She is a Distinguished Professor of Molecular, Cell, and Developmental Biology at the University of California, Santa Cruz.
Greider discovered ...
, and
Jack Szostak
Jack William Szostak (born November 9, 1952) is a Canadian American biologist of Polish British descent, Nobel Prize laureate, university professor at the University of Chicago, former professor of genetics at Harvard Medical School, and Alexan ...
were awarded the
2009
2009 was designated as the International Year of Astronomy by the United Nations to coincide with the 400th anniversary of Galileo Galilei's first known astronomical studies with a telescope and the publication of Astronomia Nova by Joha ...
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
for the discovery of how chromosomes are protected by telomeres and the
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
telomerase
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...
.
Structure and function
End replication problem

During DNA replication,
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...
cannot replicate the sequences present at the
3' ends of the parent strands. This is a consequence of its unidirectional mode of DNA synthesis: it can only attach new nucleotides to an existing 3'-end (that is, synthesis progresses 5'-3') and thus it requires a
primer
Primer may refer to:
Arts, entertainment, and media Films
* ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth
* ''Primer'' (video), a documentary about the funk band Living Colour
Literature
* Primer (textbook), a te ...
to initiate replication. On the leading strand (oriented 5'-3' within the replication fork), DNA-polymerase continuously replicates from the point of initiation all the way to the strand's end with the primer (made of
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
) then being excised and substituted by DNA. The lagging strand, however, is oriented 3'-5' with respect to the replication fork so continuous replication by DNA-polymerase is impossible, which necessitates discontinuous replication involving the repeated synthesis of primers further 5' of the site of initiation (see
lagging strand replication). The last primer to be involved in lagging-strand replication sits near the 3'-end of the template (corresponding to the potential 5'-end of the lagging-strand). Originally it was believed that the last primer would sit at the very end of the template, thus, once removed, the DNA-polymerase that substitutes primers with DNA (DNA-Pol δ in eukaryotes) would be unable to synthesize the "replacement DNA" from the 5'-end of the lagging strand so that the template nucleotides previously paired to the last primer would not be replicated. It has since been questioned whether the last lagging strand primer is placed exactly at the 3'-end of the template and it was demonstrated that it is rather synthesized at a distance of about 70–100 nucleotides which is consistent with the finding that DNA in cultured human cell is shortened by 50–100
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s per
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
.
If coding sequences are degraded in this process, potentially vital genetic code would be lost. Telomeres are non-coding, repetitive sequences located at the termini of linear chromosomes to act as buffers for those coding sequences further behind. They "cap" the end-sequences and are progressively degraded in the process of DNA replication.
The "end replication problem" is exclusive to linear chromosomes as circular chromosomes do not have ends lying without reach of DNA-polymerases. Most
prokaryote
A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...
s, relying on circular chromosomes, accordingly do not possess telomeres. A small fraction of
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
l chromosomes (such as those in ''
Streptomyces
''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...
'', ''
Agrobacterium
''Agrobacterium'' is a genus of Gram-negative bacteria established by Harold J. Conn, H. J. Conn that uses horizontal gene transfer to cause tumors in plants. ''Agrobacterium tumefaciens'' is the most commonly studied species in this genus. ''Agr ...
'', and ''
Borrelia
''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted by ticks. Other species of ''Borrelia'' cause relapsing fever, and are ...
''), however, are linear and possess telomeres, which are very different from those of the eukaryotic chromosomes in structure and function. The known structures of bacterial telomeres take the form of
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
bound to the ends of linear chromosomes, or hairpin loops of single-stranded DNA at the ends of the linear chromosomes.
Telomere ends and shelterin

At the very 3'-end of the telomere there is a 300 base pair overhang which can invade the double-stranded portion of the telomere forming a structure known as a T-loop. This loop is analogous to a knot, which stabilizes the telomere, and prevents the telomere ends from being recognized as breakpoints by the DNA repair machinery. Should non-homologous end joining occur at the telomeric ends, chromosomal fusion would result. The T-loop is maintained by several proteins, collectively referred to as the shelterin complex. In humans, the shelterin complex consists of six proteins identified as
TRF1
The TRF1, originally known as GIAT 155 mm Tracté (TR) is a 155mm French towed howitzer produced by Nexter (ex Giat Industries) and used by the French Army.
The TRF1 was showcased in 1979 at the Eurosatory arms trade show, as a replacement for ...
,
TRF2,
TIN2,
POT1
Protection of telomeres protein 1 is a protein that in humans is encoded by the ''POT1'' gene.
Function
This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein fu ...
,
TPP1, and
RAP1
Rap1 (Ras-proximate-1 or Ras-related protein 1) is a small GTPase, which are small cytosolic proteins that act like cellular switches and are vital for effective signal transduction. There are two isoforms of the Rap1 protein, each encoded by ...
.
In many species, the sequence repeats are enriched in
guanine
Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...
, e.g. TTAGGG in
vertebrate
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
s,
which allows the formation of
G-quadruplex
In molecular biology, G-quadruplex secondary structures (G4) are formed in nucleic acids by sequences that are rich in guanine. They are helical in shape and contain guanine tetrads that can form from one, two or four strands. The unimolecular ...
es, a special conformation of DNA involving non-Watson-Crick base pairing. There are different subtypes depending on the involvement of single- or double-stranded DNA, among other things. There is evidence for the 3'-overhang in
ciliate
The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to flagellum, eukaryotic flagella, but are in general shorter and present in much larger numbers, with a ...
s (that possess telomere repeats similar to those found in
vertebrate
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
s) to form such G-quadruplexes that accommodate it, rather than a T-loop. G-quadruplexes present an obstacle for enzymes such as DNA-polymerases and are thus thought to be involved in the regulation of replication and transcription.
Telomerase

Many organisms have a ribonucleoprotein enzyme called telomerase, which carries out the task of adding repetitive nucleotide sequences to the ends of the DNA. Telomerase "replenishes" the telomere "cap" and requires no ATP.
In most multicellular eukaryotic organisms, telomerase is active only in
germ cell
A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...
s, some types of
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s such as
embryonic stem cells
Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...
, and certain
white blood cell
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s. Telomerase can be reactivated and telomeres reset back to an embryonic state by
somatic cell nuclear transfer
In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking a denucleated oocyte (egg cell) and implanti ...
. The steady shortening of telomeres with each replication in somatic (body) cells may have a role in
senescence
Senescence () or biological aging is the gradual deterioration of Function (biology), functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate, death rates or a decrease in fecundity with ...
and in the prevention of
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. This is because the telomeres act as a sort of time-delay "fuse", eventually running out after a certain number of cell divisions and resulting in the eventual loss of vital genetic information from the cell's chromosome with future divisions.
Length
Telomere length varies greatly between species, from approximately 300
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s in yeast to many kilobases in humans, and usually is composed of arrays of
guanine
Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...
-rich, six- to eight-base-pair-long repeats. Eukaryotic telomeres normally terminate with
3′ single-stranded-DNA overhang ranging from 75 to 300 bases, which is essential for telomere maintenance and capping. Multiple proteins binding single- and double-stranded telomere DNA have been identified. These function in both telomere maintenance and capping. Telomeres form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle, stabilized by
telomere-binding protein
Telomere-binding proteins (also known as TERF, TRBF, TRF) function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TERF1) and TTAGGG repeat binding factor-2 ( TERF2). Tel ...
s. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA, and base pairing to one of the two strands. This triple-stranded structure is called a
displacement loop
In molecular biology, a displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA. An R-loop is similar to a D-loop, but in that case ...
or D-loop. A recent 2025 study suggest individuals with higher
vitamin D
Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...
intake may experience a slower rate of
cellular aging. The study found that vitamin D supplements could help reduce this shortening, potentially by lowering
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. However, scientists caution that vitamin D is not a universal remedy, as it does not appear to impact all chronic illnesses.
Shortening
Oxidative damage
Apart from the end replication problem,
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
studies have shown that telomeres accumulate damage due to
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
and that oxidative stress-mediated DNA damage has a major influence on telomere shortening
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
. There is a multitude of ways in which oxidative stress, mediated by
reactive oxygen species
In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...
(ROS), can lead to DNA damage; however, it is yet unclear whether the elevated rate in telomeres is brought about by their inherent susceptibility or a diminished activity of DNA repair systems in these regions. Despite widespread agreement of the findings, widespread flaws regarding measurement and sampling have been pointed out; for example, a suspected species and tissue dependency of oxidative damage to telomeres is said to be insufficiently accounted for. Population-based studies have indicated an interaction between anti-oxidant intake and telomere length. In the Long Island Breast Cancer Study Project (LIBCSP), authors found a moderate increase in breast cancer risk among women with the shortest telomeres and lower dietary intake of beta carotene, vitamin C or E. These results
suggest that cancer risk due to telomere shortening may interact with other mechanisms of DNA damage, specifically oxidative stress.
Association with aging
Although telomeres shorten during the lifetime of an individual, it is telomere shortening-rate rather than telomere length that is associated with the human lifespan.
Critically short telomeres trigger a
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
response and
cellular senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of appro ...
.
Mice have much longer telomeres, but a greatly accelerated telomere shortening-rate and greatly reduced lifespan compared to humans and elephants.
Telomere shortening is associated with aging, mortality, and aging-related diseases in experimental animals.
Although many factors can affect human lifespan, such as smoking, diet, and exercise, as persons approach the upper limit of human
life expectancy
Human life expectancy is a statistical measure of the estimate of the average remaining years of life at a given age. The most commonly used measure is ''life expectancy at birth'' (LEB, or in demographic notation ''e''0, where '' ...
, longer telomeres may be associated with lifespan.
However, vitamin D3 supplementation has been shown to significantly reduce telomere shortening over four years compared to a placebo, thus preventing nearly three years' worth of cellular aging, which may help offset telomere truncation over time.
Potential effect of psychological stress
Meta-analyses
Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...
found that increased perceived
psychological stress
In psychology, stress is a feeling of emotional strain and pressure. Stress is a form of psychological and mental discomfort. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the envi ...
was associated with a small decrease in telomere length—but that these associations attenuate to no significant association when accounting for
publication bias
In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a Statistical significance, significant find ...
. The literature concerning telomeres as integrative biomarkers of exposure to stress and adversity is dominated by cross-sectional and correlational studies, which makes causal interpretation problematic.
A 2020 review argued that the relationship between psychosocial stress and telomere length appears strongest for stress experienced in utero or early life.
Lengthening
The phenomenon of limited cellular division was first observed by
Leonard Hayflick
Leonard Hayflick (May 20, 1928 – August 1, 2024) was an American anatomist who was Professor of Anatomy at the UCSF School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. He was also past pr ...
, and is now referred to as the
Hayflick limit.
Significant discoveries were subsequently made by a group of scientists organized at
Geron Corporation
Geron Corporation is a biotechnology company located in Foster City, California which specializes in developing and commercializing therapeutic products for cancer that inhibit telomerase.
Company information
Geron, based in Foster City, Cal ...
by Geron's founder
Michael D. West
Michael D. West (born 28 April 1953 in Niles, Michigan) is an American biogerontologist, and a pioneer in stem cells, cellular aging and telomerase. He is the founder and CEO of AgeX Therapeutics,
a startup focused on the field of experimental ...
, that tied telomere shortening with the Hayflick limit.
The cloning of the catalytic component of telomerase enabled experiments to test whether the expression of telomerase at levels sufficient to prevent telomere shortening was capable of immortalizing human cells. Telomerase was demonstrated in a 1998 publication in ''
Science
Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
'' to be capable of extending cell lifespan, and now is well-recognized as capable of immortalizing human somatic cells.
Two studies on long-lived
seabird
Seabirds (also known as marine birds) are birds that are adaptation, adapted to life within the marine ecosystem, marine environment. While seabirds vary greatly in lifestyle, behaviour and physiology, they often exhibit striking convergent ...
s demonstrate that the role of telomeres is far from being understood. In 2003, scientists observed that the telomeres of
Leach's storm-petrel
Leach's storm petrel or Leach's petrel (''Hydrobates leucorhous'') is a small seabird of the tubenose order. It is named after the British zoologist William Elford Leach. The scientific name is derived from Ancient Greek. ''Hydrobates'' is from ...
(''Oceanodroma leucorhoa'') seem to lengthen with chronological age, the first observed instance of such behaviour of telomeres.
A study reported that telomere length of different mammalian species correlates inversely rather than directly with lifespan, and concluded that the contribution of telomere length to lifespan remains controversial. There is little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.
Sequences
Experimentally verified and predicted telomere sequence motifs from more than 9000 species are collected in research community curated databas
TeloBase Some of the experimentally verified telomere
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
sequences are also listed i
Telomerase Databasewebsite (see
nucleic acid notation
The nucleic acid notation currently in use was first formalized by the International Union of Pure and Applied Chemistry (IUPAC) in 1970. This universally accepted notation uses the Roman characters G, C, A, and T, to represent the four nucleotides ...
for letter representations).
Research on disease risk
Preliminary research indicates that disease risk in aging may be associated with telomere shortening,
senescent cell
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approxim ...
s, or SASP (
senescence-associated secretory phenotype
Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosome ...
).
Measurement
Several techniques are currently employed to assess average telomere length in eukaryotic cells. One method is the Terminal Restriction Fragment (TRF) southern blot. There is a Web-based Analyser of the Length of Telomeres
WALTER, software processing the TRF pictures. A Real-Time
PCR assay for telomere length involves determining the Telomere-to-Single Copy Gene (T/S) ratio, which is demonstrated to be proportional to the average telomere length in a cell.
Tools have also been developed to estimate the length of telomere from
whole genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing or just genome sequencing, is the process of determining the entirety of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's ...
(WGS) experiments. Amongst these are TelSeq, Telomerecat and telomereHunter. Length estimation from WGS typically works by differentiating telomere sequencing reads and then inferring the length of telomere that produced that number of reads. These methods have been shown to correlate with preexisting methods of estimation such as PCR and TRF.
Flow-FISH
Flow-FISH (fluorescence in-situ hybridization) is a cytogenetic technique to quantify the copy number of RNA or specific repetitive elements in genomic DNA of whole cell populations via the combination of flow cytometry with cytogenetic fluorescent ...
is used to quantify the length of telomeres in human white blood cells. A semi-automated method for measuring the average length of telomeres with Flow FISH was published in Nature Protocols in 2006.
While multiple companies offer telomere length measurement services, the utility of these measurements for widespread clinical or personal use has been questioned. Nobel Prize winner
Elizabeth Blackburn
Elizabeth Helen Blackburn (born 26 November 1948) is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the ...
, who was co-founder of one company, promoted the clinical utility of telomere length measures.
In wildlife
During the last two decades, eco-evolutionary studies have investigated the relevance of life-history traits and environmental conditions on telomeres of wildlife. Most of these studies have been conducted in
endotherm
An endotherm (from Greek ἔνδον ''endon'' "within" and θέρμη ''thermē'' "heat") is an organism that maintains its body at a metabolically favorable temperature, largely by the use of heat released by its internal bodily functions inst ...
s, i.e. birds and mammals. They have provided evidence for the inheritance of telomere length; however,
heritability
Heritability is a statistic used in the fields of Animal husbandry, breeding and genetics that estimates the degree of ''variation'' in a phenotypic trait in a population that is due to genetic variation between individuals in that population. T ...
estimates vary greatly within and among species. Age and telomere length often negatively correlate in vertebrates, but this decline is variable among taxa and linked to the method used for estimating telomere length. In contrast, the available information shows no sex differences in telomere length across vertebrates. Phylogeny and life history traits such as body size or the pace of life can also affect telomere dynamics. For example, it has been described across species of birds and mammals. In 2019, a meta-analysis confirmed that the exposure to stressors (e.g. pathogen infection, competition, reproductive effort and high activity level) was associated with shorter telomeres across different animal taxa.
Studies on
ectotherm
An ectotherm (), more commonly referred to as a "cold-blooded animal", is an animal in which internal physiological sources of heat, such as blood, are of relatively small or of quite negligible importance in controlling body temperature.Dav ...
s, and other non-mammalian organisms, show that there is no single universal model of telomere erosion; rather, there is wide variation in relevant dynamics across
Metazoa
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia (). With few exceptions, animals consume organic material, breathe oxygen, have myocytes and are able to move, can reproduce sexually, and grow from a hol ...
, and even within smaller taxonomic groups these patterns appear diverse.
See also
*
Epigenetic clock
An epigenetic clock is a Biomarkers of aging, biochemical test that can be used to measure age. The test is based on modifications that change over time and regulate how genes are expressed. Typically, the test examines DNA methylation levels, meas ...
*
Centromere
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fiber ...
*
DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of DNA damage (naturally occurring), naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although ...
*
Immortality
Immortality is the concept of eternal life. Some species possess "biological immortality" due to an apparent lack of the Hayflick limit.
From at least the time of the Ancient Mesopotamian religion, ancient Mesopotamians, there has been a con ...
*
Maximum life span
Maximum life span (or, for humans, maximum reported age at death) is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maxi ...
*
Rejuvenation (aging)
Rejuvenation is a medical discipline focused on the practical reversal of the aging process.
Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes to slow aging. ...
*
Senescence
Senescence () or biological aging is the gradual deterioration of Function (biology), functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate, death rates or a decrease in fecundity with ...
, biological aging
*
Tankyrase
Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the ''TNKS'' gene. It inhibits the binding of TERF1 to telomeric DNA.
Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 an ...
*
Telomere-binding protein
Telomere-binding proteins (also known as TERF, TRBF, TRF) function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TERF1) and TTAGGG repeat binding factor-2 ( TERF2). Tel ...
*
G-quartet
*
Immortal DNA strand hypothesis
The immortal DNA strand hypothesis posits that adult stem cells replicate their DNA asymmetrically to minimize mutations in their genomes. It was proposed in 1975 by John Cairns as a mechanism that would benefit organisms by reducing cancer incide ...
Notes
References
External links
Telomeres and Telomerase: The Means to the EndNobel Lecture by
Elizabeth Blackburn
Elizabeth Helen Blackburn (born 26 November 1948) is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the ...
, which includes a reference to the impact of stress, and pessimism on telomere length
Telomerase and the Consequences of Telomere DysfunctionNobel Lecture by
Carol Greider
Carolyn Widney Greider (born April 15, 1961) is an American molecular biologist and Nobel laureate. She is a Distinguished Professor of Molecular, Cell, and Developmental Biology at the University of California, Santa Cruz.
Greider discovered ...
DNA Ends: Just the BeginningNobel Lecture by
Jack Szostak
Jack William Szostak (born November 9, 1952) is a Canadian American biologist of Polish British descent, Nobel Prize laureate, university professor at the University of Chicago, former professor of genetics at Harvard Medical School, and Alexan ...
{{Authority control
Chromosomes
Molecular biology
Repetitive DNA sequences
Non-coding DNA