Birthweight may influence the rate of aging

According to an article published in the International Journal of Epidemiology, certain blood metabolites resulting from molecular changes before birth or in early childhood can predict health and aging rate in adult life. Researchers at King’s College London have developed a technique called metabolomic profiling which revealed a series of over 20 metabolites related to aging. It seems that some of them that are related to aging (such as bone mineral density and lung function) are associated with birthweight, which is known to be a determinant of healthy aging.

Professor Tim Spector, Head of the Department of Twin Research at King’s College London, said that researchers have long known that the birthweight of a person is a determinant of health; the fact that people who had low birthweight are more prone  to age-related diseases proves this hypothesis. He added that so far the molecular mechanisms by which low birthweight is related to age-related diseases remain incompletely understood, but now the study revealed one of these mechanisms.

Baby

Scientists from the Department of Twin Research at King’s identified by metabolomic profiling several metabolites (markers left behind in the blood by various cellular processes) linked to aging and weightbirth. They have identified 22 such  markers after analyzing blood samples from 6,000 twins. It seems that the concentration of these metabolites was higher in older people than in the young. One of these metabolites, called C-glyTrp, is associated with low weightbirth and with a number of age-related disease such as low bone mineral density, blood pressure, blood cholesterol and lung function. “This may help us understand how lower nutrition in the womb alters molecular pathways that result in faster ageing and a higher risk of age-related diseases fifty years later”, researchers said.

To learn more about this marker and birthweight, researchers have shown through genetic testing that the gene that dictates the level of this metabolite may be influenced by epigenetic changes. Lifestyle and environmental factors can activate or deactivate certain genes and this may influence the risk of age-related disease. Lead researcher from King’s, Ana Vlades, said that the aging process is influenced by several factors (genetic, environmental, lifestyle) and that genes influence is only part of the process. She also pointed out that the molecular changes that dictate how we age are triggered by epigenetic changes. Researchers believe that these markers could be detected in the future using simple blood tests and will provide valuable information about the aging process and possible therapies to treat age-related diseases.

Phthalates may affect fertility in women, according to study

A new study led by researchers from Massachusetts General Hospital and Harvard Medical School in Boston, USA, suggests that phthalates, chemicals found in plastics and cosmetics, may be a cause of low fertility in women undergoing in vitro fertilization. Phthalates effects on fertility have been highlighted by several studies in the past as these compounds have been identified as potential environmental factors of infertility; this is why they are called “endocrine disruptors”.

Phthalates are esters of phthalic acid and are found in a wide range of products: plastics, pharmaceuticals, paints, textiles, detergents, etc.. There are two types of phthalates: phthalates are used to manufacture plastic products (high molecular weight phthalates) and phthalates that are used to manufacture cosmetics (low molecular weight phthalates). Although there have been many studies that have shown the effects of phthalates on male fertility (it looks like it drops the quality and quantity of semen), there is very little information on low-level, daily exposures to phthalates on the female reproductive system.

fertility

 Dr. Souter, from Massachusetts General Hospital and Harvard Medical School in Boston, USA, believes that exposure to phthalates can lead to specific adverse effects on female reproductive system. To verify this hypothesis, the researchers conducted a study on 231 women undergoing IVF at the Massachusetts General Hospital between 2004 and 2012. The researchers wanted to identify the effects of exposure to phthalates, therefore they took urine samples at the beginning and end of treatment to identify metabolites derived from phthalates.

To assess the relationship between the levels of urinary metabolites and the effects on female reproductive system, researchers analyzed three markers of response to IVF: the number of eggs produced after hormonal treatment for IVF, embryo development and implantation failure. The results showed that exposure to phthalates was widespread as urinary metabolites were detected in almost all the women who took part in the study. Results showed that implantation failure rate was directly proportional to the level of urinary phthalate metabolites. It was also found that the number of oocytes retrieved was lower as the level of urinary phthalate metabolites was higher. However, the researchers found no association between urinary levels of phthalates and rates of fertilization or embryo development.

Dr Souter believes that these results confirm the hypothesis that phthalates are widespread in the environment and can have adverse effects on female fertility. “We are all primarily exposed to phthalates through inhalation and ingestion.  “It is extremely difficult if not impossible to avoid exposure to phthalates, since they are in so many products”, Dr. Souter said.

New genome analysis technique increases the rate of pregnancy success after IVF

Researchers at the University of Oxford have announced that the first birth in which was applied for the first time “next generation sequencing”, has been successfully achieved. NGS, next generation sequencing, is a promising analytical technique for the diagnosis of genetic mutations, chromosomal abnormalities and mitochondrial disorders. Dr Wells, who led the international research team behind the study, said the next generation sequencing offers an unprecedented view into the biology of embryos.

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IVF is the only solution for infertile couples who want to have children. However,there may be necessary several attempts in order to obtain a viable pregnancy. Identification of the embryos remains the most difficult part because only 30% of embryos selected for transfer become implanted in the uterus. Researchers do not know why the failure rate is so high but it is assumed that genetic defects and chromosomal abnormalities are the cause. To increase the success rate of IVF, scientists have created various screening methods to detect the most viable embryos, but the randomized clinical trials have shown that these techniques have many disadvantages.

Embryo

It seems that the new NGS shows no disadvantages of previous screening. First, NGS provides complete information about possible chromosomal abnormalities that can lead to miscarriage, and can simultaneously detect genetic mutations. Second, another advantage is that the NTSB analysis is more rapidly, it takes about 16 hours, which means it is no longer necessary freezing the embryo while waiting the results. In addition, it reduces the cost of the screening test of the embryos, which is currently quite expensive.

To see which is the accuracy and predictability of NGS in screening embryos, the researchers made a study on embryos and the results have been validated on many multiple cells from cell-lines with known mitochondrial DNA mutations, chromosomal abnormalities and genetic mutations. After demonstrated the accuracy of the procedure, the researchers applied clinically the method on samples of cells harvested from 7 blastocyst (five-day-old embryo) from two couples  undergoing IVF.

NGS analysis identified 3 respectively 2 healthy embryos, and, based on these results, researchers performed single embryo transfers that resulted in healthy pregnancies in both cases. The first pregnancy ended with delivery of a healthy boy  in June. Dr. Wells said that many of the embryos produced during infertility treatments had no chance to become babies because of lethal genetic mutations. Next generation sequencing improves the ability to identify these abnormalities and to detect embryos with the best chance of producing a viable pregnancy.

CHARGE syndrome is the acronym for a rare genetic disease that includes several defects: coloboma, heart defects, atresia choanae, retardation, genital and urinary tract defects and ear abnormalities. This syndrome is caused by mutation of a gene that is found on chromosome 8, called CHD7, which plays an important role in the activation and deactivation of other genes. Not many details are known about the mutation of this gene even though it is known that it leads to a wide range of defects. It should be noted that CDH7 is implicated in several cancers; colon cancer, lung or brain tumors express mutations of this gene.

It seems that CHD7 encodes an epigenetic regulator that plays an important role in remodeling of chromatin and nucleosomes (which are DNA structures). Epigenetic regulators like CDH7 are essential for creating some nucleosome-free regions in the gene structure. Therefore, the mutation of CDH7 may cause other misregulated genes. Haikun Dr. Liu’s lab at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), is investigating adult neural stem cells and their role in human diseases such as brain tumors and mental retardation. A group of patients with mental retardation and developmental disabilities are the patients with CHARGE syndrome. And it seems that what underlies this syndrome is a central nervous defect.

To better understand the role of CDH7 mutation in CHARGE syndrome, the researchers made several experiments on genetically modified mice. They switched off uniquely CHD7 gene in neural stem cells in different stages of neurodevelopment, allowing researchers to see how cells evolve without CDH7. Scientists have observed that in both fetal and adult neural stem cells, switching off CHD7 prevented cells to develop into mature neurons, which are morpho-functional units of the brain. Neurons are complex structures that are interconnected by synapses, which form networks in the brain. It seems that the mutant form of CHD7 prevent neurons to form these networks.

What is interesting is that the researchers found that exercise resulted in the recovery of CHD7 deficient animals. After practicing on a running wheel, rodents were completely recovered. The role of running in neuronogenesis was demonstrated in both animals and humans. Researchers now believe that this discovery will lead to a better understanding of CHARGE syndrome and a potential treatment to improve symptoms in humans. “We were extremely excited to see that the CHD7 deficiency in a cell can be bypassed via an unknown mechanism provoked by exercise involving running. Now, we are eagerly working to find the underlying mechanism,” says Haikun Liu.

Study finds that some of the IVF treatments increase the risk of autism

Couple infertility, the inability to conceive a baby, has greatly increased in recent decades, as well as the number of vitro fertilization treatments. Although IVF is the only solution for some couples to have a child, it yet has some risks. Researchers have now found that IVF treatments for the most severe forms of male infertility are associated with a higher risk of autism and intellectual disability in children. The risks of modern treatment with IVF are presented in the largest survey of IVF carried out by researchers at King’s College London (UK), in collaboration with scientists at Karolinska Institutet (Sweden) and Mount Sinai School of Medicine in New York ( USA), and published in the Journal of the American Medical Association.

The researchers investigated more than 2.5 million birth records (between 1982 and 2007) and followed children until 2009 to see if they have been diagnosed with autism or intellectual disability (defined as having IQ Below 70 years). It was found that 30,959, or 1.2%, were conceived using IVF, and, of these, 103 were diagnosed with autism (out of 6959), and 180 were diagnosed with intellectual disability (out of 15 , 830 children). The researchers also compared with single births and multiple births because it is  known that the latter is a risk factor for neurodevelopmental disorders.

IVF

Co-author of the study from King’s College London’s Institute of Psychiatry, Sven Sandin said that treatments for infertility are quite varied and complex. He explained that when they looked at IVF treatments combined, there was no difference noted between normal births and IVF except a slightly increased risk for intellectual disability, but when looked at IVF following ICSI, the risk of autism and intellectual disability in children was greatly increased. ICSI (intracytoplasmic Sperm Injection) is an in vitro fertilization procedure in which a single sperm is injected directly into the egg and is a technique that is used in male infertility.

Regarding the risk of intellectual disability, it seems that IVF is associated with a slightly increased risk of intellectual disability in children compared with normal births: from 39.8 to 46.3 per 100,000 person years, so a 18% higher risk. To determine the risk of autism and intellectual disability in children conceived by IVF treatments, the researchers investigated whether there were used fresh or frozen embryos, intracytoplasmic sperm injection (ICSI) or whether sperm was ejaculated or surgically extracted. It was found that the risk of autism and intellectual disability in children is significantly increased after ICSI IVF treatments: 51% from 62 to 93 per 100,000. “Our study shows that treatments developed to manage male infertility are associated with an increased risk for developmental disorders in the offspring”, said Dr Avi Reichenberg, who led the study from King’s College London’s Institute of Psychiatry and Mount Sinai School of Medicine.

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Researchers explain the ‘amotivational syndrome’ in cannabis users

According to a study published in the journal Biological Psychiatry, cannabis leads to decreased motivation when consumed for a long time due to reduction of dopamine in the brain. It seems that researchers at Imperial College London, UCL and King’s College London, found that those who frequently consume cannabis or those who started using cannabis at a young age, have low levels of dopamine in the striatum (a subcortical part of the forebrain). This could be the explanation for the fact that cannabis is associated with a lack of motivation.

Although the study was done on a small number of patients (19 regular cannabis users and 19 non-users), the results showed low levels of dopamine in those who started consuming cannabis early. Using PET brain imaging, researchers were able to see how cannabis affects dopamine levels in the striatum. All cannabis users explained that, during smoking, they had experienced psychotic symptoms and strange sensations such as they had been threatened by an unknown force. Based on these data, researchers expected to find high levels of dopamine in these individuals, but the results showed that, on the contrary, dopamine levels were low.

cannabis

First contact with cannabis (those included in the study) was between 12 and 18 years and it was found that those who started cannabis early, as well as those who consumed frequently, had lower levels of dopamine. The lowest levels of dopamine were found in those who met the criteria for dependence or abuse of cannabis, and this finding led researchers to think that dopamine levels may be a marker of addiction. Dr Michael Bloomfield, from the Institute of Clinical Sciences at Imperial, who led the study, said the results were not the ones they expected but they correlate with other studies that point out that substance abusers (cocaine, methamphetamine) have altered levels of dopamine. “It has been assumed that cannabis increases the risk of schizophrenia by inducing the same effects on the dopamine system that we see in schizophrenia, but this hasn’t been studied in active cannabis users until now,” said Dr. Bloomfield.

The effect of cannabis has been highlighted by other studies that have shown that people who consume this recreational drug have an increased risk of mental illnesses and episodes of psychosis (schizophrenia, for example). The first psychoactive effect of cannabis include euphoria and relaxation (caused by a compound called tetrahydrocannabinol), then it comes a state of introspection that can result in paranoia and anxiety.

Fear dictates the way we perceive sounds

It is known that hearing a Mozart sonata influences our emotions and inner state, but now researchers have shown that this could also work the other way. In other words our inner emotions can dictate the way we perceive a melody. If we associate emotions with certain sounds, these sounds can arouse those emotions which were first associated with. Post-traumatic stress disorder (PTSD), as it is called this phenomenon is common in some war veterans who still have strong memories of the battlefield when hearing certain sounds.

However, researchers cannot clearly explain what are the mechanisms underlying this association. Therefore a team of researchers from the Perelman School of Medicine at the University of Pennsylvania have deepened this field and found that fear can increase or decrease the ability to discriminate sounds depending on situation. Senior study author Maria N. Geffen, PhD, assistant professor of Otorhinolaryngology: Head and Neck Surgery and Neuroscience at Penn, said that emotions are closely linked to perception and emotional response helps us face reality. For example, a fear response helps us escape from a dangerous situation and act quickly. But there are situations where things go wrong because of fear. It happens in anxiety or PTSD.

Fear

Researchers conducted several experiments on mice to investigate how auditory acuity may change after an unpleasant event. These experiments are based on a process called emotional learning (which is built on classical conditioning, or Pavlovian) and investigate how animals can learn to distinguish between potential hazards and safe sound (“emotional discrimination learning”). Because this type of conditioning usually leads to poor learning, Geffen and Mark Aizenberg, PhD, the first author of the study, created a series of tasks designed to lead to a better emotional discrimination in mice. What interested the researchers was to discover how emotions can affect sound perception and discrimination.

Geffen said that ‘animals presented with the two sounds that were very similar exhibited specialization of their emotional response, while animals presented with sounds that were very far apart generalize the fear that they developed to the danger tone over a whole range of frequencies”. It seems that the effects of emotional learning on auditory perception are processed by the auditory cortex, a brain region that has several roles including the auditory plasticity. What surprised the researchers was that emotional learning is not mediated by this region (the auditory cortex), but by the amygdala and other sub-cortical auditory areas.

Fatty acids lower risk of Breast Cancer

Researchers made new discoveries about breast cancer: fatty acids, more exactly n-3 polyunsaturated fatty acid (n-3 PUFA) from fish, lower the risk of breast cancer by 5%. Statistics show that breast cancer, along with skin cancer, is the most common form of cancer in women. According to statistics from 2008, breast cancer accounted for about 13% of all cancers and was responsible for approximately 14% of all cancer deaths. However, breast cancer incidence began to decline in recent years by about 2% per year.

Over time, studies have revealed several risk factors for breast cancer. It seems that the most important risk factor is age: as you grew older, with the risk of breast cancer is higher ( as it is with any type of cancer). Also, the risk of this cancer doubles if there is a first degree family relative (mother, sister, daughter) who had breast cancer. Genetic causes account for about 10% of all breast cancers and the most known genes are BRCA1, BRCA2, which increase the risk not only of breast cancer but also for ovarian cancer. It also should be noted that women who carry mutations of these genes have an increased risk of developing breast cancer at a much younger age.

Breast Cancer

In terms of protective factors, it appears that a balanced diet and a healthy lifestyle are essential in preventing breast cancer. However these are generally recommended not only for cancer prevention but also for cardiovascular diseases. However it seems, as far as diet is concerned, dietary fat is one that has the most important role in lowering the risk of breast cancer. There are several types of n-3 PUFAS  (ALA, EPA, DPA and DHA) that are involved in immune defense, chemical signaling in the brain, regulating the activity of blood vessels, etc.. Fish oil is the best source of EPA, DPA and DHA, while nuts, seeds, and leafy green vegetables contain mostly ALA.

Because studies in humans have been inconclusive, a team of researchers wanted to see if indeed these fatty acids decrease the risk of breast cancer. They measured the levels of these acids in both blood and dietary sources. After analyzing 26 studies from the United States, Europe and Asia, including more than 20 000 cases of breast cancer, the researchers concluded that marine n-3 PUFA reduces the risk of breast cancer by 14% . In addition, it appears that Asian women have the lowest risk for breats cancer because fish intake is much higher here than in other regions.

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