US scientists have found that children with older fathers and grandfathers appear to be “genetically programmed” to live longer.
The genetic make-up of sperm changes as a man ages and develops DNA code that favors a longer life – a trait he then passes to his children.
The team found the link after analyzing the DNA of 1,779 young adults.
Their work appears in Proceedings of the National Academy of Sciences.
Experts have known for some time that lifespan is linked to the length of structures known as telomeres that sit at the end of the chromosomes that house our genetic code, DNA. Generally, a shorter telomere length means a shorter life expectancy.
Like the plastic tips on shoelaces, telomeres protect chromosomal ends from damage. But in most cells, they shorten with age until the cells are no longer able to replicate.
US scientists have found that children with older fathers and grandfathers appear to be "genetically programmed" to live longer
However, scientists have discovered that in sperm, telomeres lengthen with age.
And since men pass on their DNA to their children via sperm, these long telomeres can be inherited by the next generation.
Dr. Dan Eisenberg and colleagues from the Department of Anthropology at Northwestern University studied telomere inheritance in a group of young people living in the Philippines.
Telomeres, measured in blood samples, were longer in individuals whose father’s were older when they were born.
The telomere lengthening seen with each year that the men delayed fatherhood was equal to the yearly shortening of telomere length that occurs in middle-aged adults.
Telomere lengthening was even greater if the child’s paternal grandfather had also been older when he became a father.
Although delaying fatherhood increases the risk of miscarriage, the researchers believe there may be long-term health benefits.
Inheriting longer telomeres will be particularly beneficial for tissues and biological functions that involve rapid cell growth and turnover – such as the immune system, gut and skin – the scientists believe.
And it could have significant implications for general population health.
“As paternal ancestors delay reproduction, longer telomere length will be passed to offspring, which could allow life span to be extended as populations survive to reproduce at older ages.”
It might be possible that the advantage of receiving long telomeres from an old father is more then set off by the disadvantage of higher levels of general DNA damage and mutations in sperm, he said.
Scientists say life expectancy is written into our DNA and could be seen from the day we are born.
They have found a way to predict how long someone will live – by measuring their genes as a baby
It all depends on the length of the telomeres, which are described as “acting like the plastic ends on shoelaces” to protect chromosomes from wear and tear.
Telomeres are being studied extensively – and are thought to hold the key to ageing.
The longer your telomeres, the longer you will live – dependent, of course, on not dying accidentally, from disease or from lifestyle factors.
It was known they could be shortened by life choices, including smoking and stress. But this is the first indication that our lifespan might be predetermined from birth.
In the future, tests may allow people to know their expected lifespan from a very early age – if they want to.
Professor Pat Monaghan, who led the Glasgow University study, said: “The results of this research show that what happens in our bodies in early life is very important.
“It is not understood why there are variations of telomere length but if you had a choice, you would want to be born with longer telomeres.
“If you were to test this, I don’t think anyone would want to know – it would just make you miserable. But it must be remembered that how you live has a big effect. This isn’t quite a case of nature overtaking nurture.”
Telomeres are important because they stop DNA from unraveling, but they begin shortening from the moment we are conceived
The study – which used zebra finches, one of Australia’s most common bird species – is the first to measure telomere lengths at regular intervals through an entire life. With people, it is usually only the elderly who are studied because of the timescales involved.
Blood cell samples were taken from 99 finches, starting when they were 25 days old.
The results exceeded even the researchers’ expectations. The birds with the shortest telomeres did tend to die first – from as early as seven months after the start of the trial.
But one bird in the group with the longest telomeres survived to almost nine years old.
Professor Monaghan said: “These birds were dying of natural causes. There were no predators, no diseases and no accidental deaths. This was showing their capacity for long life.”
The results hold huge implications for humans, whose telomeres work in the same way.
Telomeres are important because they stop DNA from unraveling, but they begin shortening from the moment we are conceived.
The longer they are, the better for an individual because when they get too short, they stop working.
DNA is then no longer protected and errors begin to creep in when cells divide. When this happens – usually in middle age – the skin begins to sag and the immune system becomes less efficient. Faulty cells also lead to a growing risk of conditions such as diabetes and heart disease.
The university’s institute of biodiversity, animal health and comparative medicine has published its groundbreaking research in the Proceedings of the National Academy of Sciences USA.
In the next stage of their research, the Glasgow scientists will look at what causes telomeres to shorten – including inherited and environmental factors – to make it possible to predict life expectancy more accurately.
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Progressive telomere shortening characterizes familial breast cancer patients
Telomeres, the complex structures that protect the end of chromosomes, of peripheral blood cells are significantly shorter in patients with familial breast cancer than in the general population. Results of the study carried out by the Human Genetics Group of the Spanish National Cancer Research Centre (CNIO), led by Javier Benitez, to be published in open-access journal PLoS Genetics on July 28th, reflect that familial, but not sporadic, breast cancer cases are characterized by shorter telomeres. Importantly, they also provide evidence for telomere shortening as a mechanism of genetic anticipation, the successively earlier onset of cancer down generations.
Mutations in two DNA repair genes, BRCA1 and BRCA2, characterize some, but not all, instances of hereditary breast cancer. Non-BRCA1/2 breast cancer families are heterogeneous, suggesting the existence of other genes conferring susceptibility. The group has investigated the role of telomere length in hereditary breast cancer based on previous information suggesting, first, that short telomeres and subsequent genomic instability contribute to malignant transformation; second, that genetic anticipation occurs in breast cancer families and, third, that telomere shortening is associated with anticipation in other genetic diseases. [googlead tip=”vertical_mare” aliniat=”stanga”]
By analyzing telomere length differences between mothers and daughters from breast cancer families, the authors demonstrated that genetic anticipation is associated with a decrease in telomere length in affected daughters relative to their mothers.
The results allowed the authors not only to conclude that women carrying BRCA1/2 mutation have chromosomes with short telomeres, but also to describe for the first time that genetic anticipation in breast cancer could be explained by telomere shortening. In addition, the study expands the field of research concerning genetic predisposition to breast cancer to include genes involved in telomere maintenance. The significance of generational changes in telomere length has interesting potential clinical applications in the management of familial breast cancer, and could be extended to other hereditary cancer syndromes.
FINANCIAL DISCLOSURE: This work was supported by Asociación Española Contra el Cancer (AECC) and Spanish Fondo de Investigaciones Sanitarias (grant numbers FISPI081298 and FIS-PI081120). The CIBER de Enfermedades Raras is an initiative of the ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Martinez-Delgado B, Yanowsky K, Inglada-Perez L, Domingo S, Urioste M, et al. (2011) Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer. PLoS Genet 7(7): e1002182. doi:10.1371/journal.pgen.1002182
Dr. Beatriz Martinez-Delgado and Dr. Javier Benitez
Spanish National Cancer Research Centre (CNIO)
Melchor Fernandez Almagro 3
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