Does Blood Loss Shorten Telomeres?

Does Blood Loss Shorten Telomeres?

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If blood loss necessitates immediate cell division to replace lost cells, does the increase in cell division correlate to shortening of telomeres? Does it further cause the Hayflick Limit to be reached sooner? Does blood loss accelerate apoptosis?

Nope, nope, and nope. A cursory glance over any page on hematopoesis will reveal that blood cells are replenished from HSC, hematopoetic stem cells, which are self-renewing stem cells. Telomerase is activated in stem cells.

Telomere Syndromes and Dyskeratosis Congenita

Telomere syndromes are inherited conditions that can cause bone marrow failure and lung disease. These syndromes vary in severity and can affect children and adults. In rare cases, a patient’s telomere syndrome may appear as a condition called dyskeratosis congenita. The condition, which makes up about 1 percent of all telomere syndromes, is characterized by abnormal findings in the skin, mouth and nails. Advances in understanding the basis of these conditions have helped physicians identify patients with dyskeratosis congenita and telomere syndromes.

Does oxidative stress shorten telomeres?

Oxidative stress shortens telomeres in cell culture, but whether oxidative stress explains variation in telomere shortening in vivo at physiological oxidative stress levels is not well known. We therefore tested for correlations between six oxidative stress markers and telomere attrition in nestling birds (jackdaws Corvus monedula) that show a high rate of telomere attrition in early life. Telomere attrition was measured between ages 5 and 30 days, and was highly variable (average telomere loss: 323 bp, CV = 45%). Oxidative stress markers were measured in blood at age 20 days and included markers of oxidative damage (TBARS, dROMs and GSSG) and markers of antioxidant protection (GSH, redox state, uric acid). Variation in telomere attrition was not significantly related to these oxidative stress markers (|r| ≤ 0.08, n = 87). This finding raises the question whether oxidative stress accelerates telomere attrition in vivo The accumulation of telomere attrition over time depends both on the number of cell divisions and on the number of base pairs lost per DNA replication and, based on our findings, we suggest that in a growing animal cell proliferation, dynamics may be more important for explaining variation in telomere attrition than oxidative stress.

Keywords: development molecular ecology nestlings somatic damage telomere attrition.

Conflict of interest statement

We declare we have no competing interests.


Telomere length at age 30…

Telomere length at age 30 days plotted against telomere length at age 5…

Association between oxidative stress variables…

Association between oxidative stress variables and telomere shortening ( n = 87). The…

Telomeres and Longevity: A Cause or an Effect?

Telomere dynamics have been found to be better predictors of survival and mortality than chronological age. Telomeres, the caps that protect the end of linear chromosomes, are known to shorten with age, inducing cell senescence and aging. Furthermore, differences in age-related telomere attrition were established between short-lived and long-lived organisms. However, whether telomere length is a "biological thermometer" that reflects the biological state at a certain point in life or a biomarker that can influence biological conditions, delay senescence and promote longevity is still an ongoing debate. We cross-sectionally tested telomere length in different tissues of two long-lived (naked mole-rat and Spalax) and two short-lived (rat and mice) species to tease out this enigma. While blood telomere length of the naked mole-rat (NMR) did not shorten with age but rather showed a mild elongation, telomere length in three tissues tested in the Spalax declined with age, just like in short-lived rodents. These findings in the NMR, suggest an age buffering mechanism, while in Spalax tissues the shortening of the telomeres are in spite of its extreme longevity traits. Therefore, using long-lived species as models for understanding the role of telomeres in longevity is of great importance since they may encompass mechanisms that postpone aging.

Keywords: age blind mole-rats (Spalax) long-lived longevity naked mole-rats telomere length telomeres.

Conflict of interest statement

The authors declare no conflict of interest.


Relative telomere length (Telomere to…

Relative telomere length (Telomere to Single copy gene (T/S) ratio) as a function…

Relative telomere length (T/S ratio)…

Relative telomere length (T/S ratio) in rat tissues. ( A ) range of…

Relative telomere length (T/S ratio)…

Relative telomere length (T/S ratio) in Spalax tissues. ( A ) range of…

Telomere length in Spalax and…

Telomere length in Spalax and rat in ( A ) muscle ( N…

Stress speeds up aging through telomere shortening

Aging and stress in the workplace: accelerated telomere shortening

Stress in the workplace occurs when there is no balance between what a person perceives the constraints are and how well they feel they can deal with them. Although stress is not a disease, prolonged exposure to it has negative effects on health. It is called chronic stress [5].

Many studies have shown a link between chronic stress in the workplace and a degradation in health. The risk to develop cardiovascular diseases increases as the capacity of the immune system decreases [6]. Although the missing link between stress and health (and aging) has not yet been singled out, we know that it tampers with cell function. However, cell environment plays an important role when regulating telomere length and telomerase activity. Researchers studied healthy women under different levels of chronic stress to determine if it had any impact on telomere length or influence on their physiological age [6].

The subjects under a more important stress had shorter telomeres. On average, there is a 550bp difference in telomere sequence length, no matter the chronological age of the subject, between the subjects undergoing high levels of stress and those with low levels of stress in the workplace [6]. The difference is linked to a 10 years increase of the biological age [6].

In the high-level stress group, telomerase activity is 48% lower than in subjects in the group with lower levels of stress. When this decrease of telomerase activity becomes chronic, it contributes to accelerated telomere shortening [6].

This proves the influence of extracellular factors, such as stress in the workplace, on telomere shortening. It would then be strongly linked to an increase in oxidative stress, a decrease of telomerase activity and an acceleration of telomere shortening. All of these would result in early cell senescence [4], which impacts the lifespan of the cells as well as the physiological age.


Embryonic stem cells, more primitive stem cells, are likely to be potentially immortal and capable of indefinite self-renewal together with the ability to differentiate and contribute to the germ line. Embryonic stem cells and undifferentiated embryonal carcinoma (EC) cells display high levels of telomerase activity and hTERT expression, both of which are rapidly downregulated during differentiation (Armstrong et al, 2005) and much lower or absent in somatic cells including stem cells in self-renewal tissues ( Figure 1 ). The downregulation of telomerase activity in differentiating EC cells was reported to be tightly correlated with histone deacetylation and DNA methylation of the TERT gene (Lopatina et al, 2003). Moreover, increased telomerase activity enhanced self-renewal ability, proliferation, and differentiation efficiency in Tert-overexpressing ES cells (Armstrong et al, 2005). High telomerase activity or the expression of TERT can therefore be regarded as a marker of undifferentiated ES cells.

In cloned animals originating from adult nuclei with shortened telomeres, telomere length in somatic cells has been found to be comparable with that in age-matched normal animals originating from a fertilised egg with long telomeres. This finding indicates that the enucleated oocyte has the ability to reset the telomere length of the nucleus derived from a donor adult somatic cell by the elongation of telomeres (Meerdo et al, 2005). Elucidation of this ‘reset' mechanism in oocytes will be a technical breakthrough in developing cloned animals.


To study both objective (event-/environment-based) and subjective (perception-based) stress, we examined 58 healthy premenopausal women who were biological mothers of either a healthy child (n = 19, “control mothers”) or a chronically ill child (n = 39, “caregiving mothers”). The latter were predicted to have, on average, greater environmental exposure to stress. Women in both groups completed a standardized 10-item questionnaire assessing level of perceived stress over the past month (13). This design allowed us to examine the importance of perceived stress and measures of objective stress (caregiving status and chronicity of caregiving stress based on the number of years since a child's diagnosis) (see Supporting Text, which is published as supporting information on the PNAS web site). All analyses were conducted controlling for age because we wanted to test for telomere shortening caused by stress independent of the women's chronological age (age was related to telomere length, r: –0.23, P < 0.04).

Each subject was 20–50 years old [mean (M) = 38 ± 6.5 years] and had at least one biological child living with her. Subjects were free of any current or chronic illness (see Supporting Text). Use of oral contraceptives was similar in the caregiver and control groups. Obesity level was quantified by body-mass index (BMI): weight (in kilograms)/[height (in meters) × height (in meters)]. Blood was drawn in a fasting state on a morning during the first 7 days of the follicular stage of the menstrual cycle.

Mean telomere length and telomerase activity were measured quantitatively in the PBMCs that were stored frozen at –80°C. Telomere length values were measured from DNA by a quantitative PCR assay that determines the relative ratio of telomere repeat copy number to single-copy gene copy number (T/S ratio) in experimental samples as compared with a reference DNA sample (14). Telomerase activity was measured by the telomerase repeat amplification protocol (15) with a commercial kit (Trapeze, Chemicon) and all values used were in the linear quantitative range. Vitamin E (alpha-tocopherol) was measured with HPLC from serum isolated from a blood sample protected by foil (ARUP Laboratories, Salt Lake City). F2-isoprostanes level, a reliable measure of oxidative stress, was quantified from a 12-hour nocturnal urine sample from a subsample of 44 of the women (urine was not collected on the first 14 subjects) by using a highly accurate and precise gas chromatographic/mass spectrometric assay (16) and adjusting for creatinine levels. An index of oxidative stress was calculated as the ratio of (isoprostanes per milligram of creatinine)/vitamin E. This index represents the net oxidative stress effect, taking into account one marker of oxidative stress and of antioxidant defenses. All statistical analyses that tested a priori hypotheses were performed with one-tailed P tests, given the directional nature of the predictions (see Supporting Text for details on methods and measures).

Telomere length, a longevity measure, may be determined early in life

Telomeres are protective caps on DNA that shorten as we grow older. Now, one of the first studies to examine telomere length (TL) in childhood finds that the initial setting of TL during prenatal development and in the first years of life may determine one's TL throughout childhood and potentially even into adulthood or older age. The study also finds that TL decreases most rapidly from birth to age 3, followed by a period of maintenance into the pre-puberty period, although it was sometimes seen to lengthen.

The study, which followed children from birth to age 9, was led by researchers at the Columbia Center for Children's Environmental Health at Columbia University Mailman School of Public Health. Results appear in the journal Psychoneuroendocrinology.

The researchers discovered that a mother's TL is predictive of newborn TL and tracks with her child's TL through pre-adolescence. While all telomeres are expected to shorten with age, the reasons why some children have telomeres that shorten faster are unknown, one explanation may be that telomeres are susceptible to environmental pollutants. It is also unknown why some children had telomeres that lengthened across the study period though it is notable that this phenomenon has also been observed in other studies.

"Given the importance of telomere length in cellular health and aging, it is critical to understand the dynamics of telomeres in childhood," says senior author Julie Herbstman, PhD, director of CCCEH and associate professor of environmental health science at Columbia Mailman School. "The rapid rate of telomere attrition between birth and age 3 years may render telomeres particularly susceptible to environmental influences during this developmental window, potentially influencing life-long health and longevity."

In the new study, researchers used polymerase chain reaction to measure TL in white blood cells isolated from cord blood and blood collected at ages 3, 5, 7, and 9, from 224 children. They also measured maternal TL at delivery in a subset of mothers.

The researchers say more research is needed to understand the biological mechanisms driving variability in the rate of TL change during the first years of life, as well as modifiable environmental factors that contribute to shifts in the rate of attrition.

Aging Cells, Aging Selves

While some telomere research may be ripe for commercialization, there is still a great deal to be learned from studying simple cells in simple organisms, Blackburn says. Blackburn’s own early research is a testament to the fact that some of the most important biological discoveries – and their eventual applications – are unanticipated.

Biologists have long pondered and pursued the causes of aging. Telomere research helps advance the idea that cellular aging may play a strong role in pacing the aging of the whole organism.

Long after James Watson and Francis Crick, and others in their wake, began unraveling the structure of the DNA double helix, the secrets of heredity and the mysteries of how DNA replicates as cells divide, scientists still had not identified molecular equipment that was capable of replicating DNA all the way out to the tips of chromosomes.

A little bit of DNA is lost from telomeres with each cell division. DNA in telomeres consists of the same, short sequence of nucleotide building blocks – in humans, it is TTAGGG – repeated over and over. The number of repeats can vary. The DNA in telomeres doesn’t encode vital genetic information. Instead, the telomere serves as an assembly point for a suite of proteins that help form protective end caps on the chromosome – like the aglets at the tips of your shoelaces. Some of this DNA is expendable.

But eventually, one would expect that the telomere would be used up. Important genomic DNA would then be lost. Blackburn decided to study telomeres – not in humans, but in a much simpler creature, a one-celled, pond-dwelling protozoan called Tetrahymena thermophila. The protozoan is so simple, it can be used to learn about biological chains of events so basic to life that they are found in life forms ranging from humans to the simplest one-celled organisms.

Blackburn wanted to know how single-celled Tetrahymena could keep reproducing without eventually going extinct due to a loss of genes. The answer – discovered by Blackburn and Greider – turned out to be telomerase. This strange enzyme is made up not only of protein, but also RNA. The RNA acts as a template for adding telomere DNA onto the chromosome tips, and may play other important roles as well. Blackburn’s lab team and others have shown that humans with inborn defects in this RNA component of telomerase have shorter telomeres.

DNA damage response links short telomeres, heart disorder in Duchenne muscular dystrophy

A new study shows that telomeres shorten without cell division in a mouse model of Duchenne muscular dystrophy. Subsequent DNA damage responses and mitochondrial dysfunction are likely cause of heart failure.

Telomeres are the protective caps on the ends of chromosomes. A new study shows that the progressive shortening of telomeres may be linked to enlarged hearts in those who have a type of muscular dystrophy.

Progressively shortening telomeres — the protective caps on the end of chromosomes — may be responsible for the weakened, enlarged hearts that kill many sufferers of Duchenne muscular dystrophy, according to a study by researchers at the Stanford University School of Medicine.

The researchers found that the shortening occurred specifically in the heart muscle cells, or cardiomyocytes, of laboratory mice bred to model the disease. The shortening triggered a DNA damage response that compromised the function of the cells’ energy generators, or mitochondria. As a result, the cardiomyocytes were unable to efficiently pump blood throughout the body.

The new study is an extension of a 2010 study published in Cell and a 2013 study published in Nature Cell Biology by the same researchers. It identifies possible new therapeutic approaches for Duchenne muscular dystrophy and is the first to connect the molecular dots between previously disparate observations in affected cells.

“This is the first time that telomere shortening has been directly linked to mitochondrial function via a DNA damage response in non-dividing cells,” said Helen Blau, PhD, professor of microbiology and immunology. “We’ve outlined the molecular steps in this process that lead to death, giving novel insights into the condition and identifying alternative strategies for heading off heart failure in human patients with Duchenne.”

The researchers used a mouse model of the disease they developed for the 2013 study that is the first to accurately recapitulate Duchenne muscular dystrophy in humans.

The ongoing shortening of the telomeres in cardiomyocytes is particularly surprising because the cells rarely divide. Telomeres naturally decrease in length with each cell division, acting as a kind of molecular clock counting down a cell’s life span. Their length is normally stable in healthy tissues that don’t divide.

“In mice, cell division in the heart normally stops within one week of birth,” said Blau, who is also the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Foundation Laboratory for Stem Cell Biology. “But we saw a proliferation-independent reduction in telomere length.”

Blau is the senior author of the study, published online Oct. 31 in the Proceedings of the National Academies of Science. Postdoctoral scholar Alex Chang, PhD, is the lead author.

Difficult condition to study

Duchenne muscular dystrophy is the most prevalent form of the heritable muscular dystrophies. It is caused by mutations in the dystrophin gene that inhibit the production of the dystrophin protein, which connects the interior cytoskeleton of the muscle cell to the outside matrix. But until recently, it’s been difficult to study because mice with the same dystrophin mutation didn’t display the same symptoms as humans.

In the 2013 study, researchers in the Blau lab found that the reason humans suffer more serious symptoms than do mice is because of differences in the average lengths of their telomeres: Mice have telomeres about 40 kilobases in length, while human telomeres range from around 5 to 15 kilobases. When the investigators introduced a second mutation in the mice that reduced telomere length to more closely match that of humans, the “humanized” animals began to display the typical symptoms of the disease, including progressive muscle weakness, enlarged hearts and significantly shortened life spans.

In particular, the researchers also observed that cardiomyocyte telomeres were significantly shorter than those in other muscle cells in the heart, such as the smooth muscle cells of the vasculature that do not require dystrophin for function. This was true not only in mice with mutated dystrophin, but also in four people with Duchenne muscular dystrophy who had recently died of cardiomyopathy. This was surprising because, although telomeres naturally shorten a bit with each round of cell division, their length is known to remain stable in non-dividing cells like cardiomyocytes.

“We knew from our previous study that telomeres play a role in the development of cardiomyopathy in Duchenne muscular dystrophy, but we didn’t know the kinetics,” said Chang. “Does this shortening occur suddenly, or gradually? Could it be possible to intervene? How exactly does it affect heart function?”

Telomere shortening in the absence of cell division

Chang investigated telomere length in the cardiomyocytes of mice lacking the dystrophin protein at one, four, eight and 32 weeks after birth. He found that, although the cells stopped dividing within one week, the telomeres continued to shorten, losing nearly 40 percent of their length by 32 weeks.

A closer investigation of the affected mouse cardiomyocytes indicated that telomere shortening correlated with increasing levels of a protein called p53 that is known to be elevated in the presence of DNA damage. P53 in turn inhibits the expression of two proteins necessary for mitochondrial replication and function.

“The decrease in the levels of these mitochondrial master regulators led to a reduction in the number of mitochondria in the cell and mitochondrial dysfunction,” said Blau. “They make less of the energy molecule ATP and have higher levels of damaging reactive oxygen species. This is what leads to the cardiomyopathy that eventually kills the mice.”

Treating 4-week-old mice with a mitochondrial-specific antioxidant limited subsequent mitochondrial damage, the researchers found.

Chang and Blau are interested in learning exactly how the absence of functional dystrophin contributes to telomere shortening in cardiomyocytes. They are also planning to investigate whether artificially lengthening the telomeres could head off heart damage in the mice.

“More research is clearly needed before we attempt to devise any new therapies for humans,” said Blau. “But these findings highlight the important role telomeres play in this and possibly many other human diseases in nondividing tissues like neurons and heart muscle.”

Other Stanford co-authors of the paper are postdoctoral scholars Sang-Ging Ong, PhD, and Edward LaGory, PhD Blau lab manager Peggy Kraft professor of radiation oncology Amato Giaccia, PhD and professor of cardiology Joseph Wu, MD, PhD.

The research was supported by the Baxter Foundation, the California Institute for Regenerative Medicine, the National Institutes of Health (grants AG044815, AG009521, NS089533, AR063963 and AG020961), a Stanford School of Medicine Dean’s Fellowship, the Canadian Institutes of Health Research and the American Heart Association.