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Preview: AGE OF THE FATHER AND THE HEALTH OF FUTURE GENERATIONS

AGE OF THE FATHER AND THE HEALTH OF FUTURE GENERATIONS



Leslie B. Raschka, MD: "The age of the father is an important determinant of the health of future generations. Children conceived by fathers older than 34 years of age are at increased risk for genetic illness due to recent mutation in the male germ cell.



Updated: 2017-08-13T04:38:44.323-07:00

 



Best Vegetable to eat and worse vegetables to eat

2013-11-09T10:51:14.527-08:00

By Dr. MercolaThere's little doubt that one of the best ways to improve your health is to make sure you're eating plenty of fresh, minimally processed high-quality vegetables, ideally locally-grown and organic, with a majority of them consumed raw (see my recommended list of vegetables below). One simple way to boost your vegetable intake is to juice them.Juicing organic vegetables is highly recommended to patients in our clinic who are working to restore or improve their health. I am firmly convinced that juicing is one of the key factors to giving you a radiant, energetic life, and truly optimal health. I simply do not know of any other single nutritional intervention that has a more profound influence on health than eating and/or juicing fresh, organic vegetables.You can review my comprehensive approach to how to juice on my vegetable juicing page. Even better, review my nutrition plan, which can help you take a comprehensive look at your overall health as it relates to food, and may even help you to change the way you think about eating.Are All Vegetables the Same?If you were to get all of your vegetables from conventionally farmed sources, this would be better for your health than eating no fresh vegetables at all. However, conventionally farmed vegetables are not your best choice. Organic vegetables are a much better option.Why?USDA Organic farmers (and many small, local organic farms working without certification) must use different standards when growing vegetables. These standards include never using:PesticidesSynthetic FertilizersSewage sludgeGenetically modified organisms (GMO)Ionizing radiationThe Environmental Protection Agency (EPA) considers 60 percent of herbicides, 90 percent of fungicides, and 30 percent of insecticides to be carcinogenic, and most are damaging to your nervous system as well. In fact, these powerful and dangerous chemicals have been linked to numerous health problems such as:NeurotoxicityDisruption of your endocrine systemCarcinogenicityImmune system suppressionMale infertility and reduced reproductive functionMiscarriagesParkinson's diseaseThis information alone should give you pause when considering whether to buy local, organic vegetables or not. But I encourage you to do further research about organic versus conventional farming conditions. I believe that after researching the facts and statistics, you'll come to the conclusion that organic vegetables are far more nutritious than conventionally farmed vegetables.Conventional Fruit and Vegetable Pesticide LoadsCertainly helpful to your decision about which vegetables should be purchased organic and which conventional veggies may be safe, is the measured pesticide loads found on conventionally farmed fruits and vegetables. So if you need to work within a certain budget, use this information to help guide you to the best choices when it comes to lowering your overall pesticide exposure.Of the 43 different fruit and vegetable categories tested by the Environmental Working Group and included in their Shoppers' Guide to Pesticides in Produce, the following 12 fruits and vegetables had the highest pesticide load, making them the most important to buy or grow organically:PeachesApplesSweet bell peppersCeleryNectarinesStrawberriesCherriesLettuceGrapes (imported)PearsSpinachPotatoesIn contrast, the following foods were found to have the lowest residual pesticide load, making them the safest bet among conventionally grown vegetables:BroccoliCabbageBananaKiwiAsparagusSweet peas (frozen)MangoPineappleSweet corn (frozen)AvocadoOnionThe Importance of Fresh VegetablesBuying your vegetables from a local organic source is the ideal way to ensure that your vegetables are both fresh and high-quality. I strongly advise you to avoid wilted vegetables of any kind, because when vegetables wilt, they lose much of their nutritional value. In fact, wilted organic vegetables may actually be less healthful than fresh conventionally farmed vegetables!Another reason to buy your organic vegetables from a local source is that fresher vegetables also contain the hig[...]



Eat Your Broccoli

2013-11-09T10:06:36.304-08:00

Eat Your BroccoliNovember 09, 2013 | 19,398 viewsBy Dr. MercolaVegetables have an impressive way of offering widespread benefits to your health, and broccoli is no exception. When you eat broccoli you’re getting dozens, maybe even hundreds, of super-nutrients that support optimal, body-wide health.Man-made substances just can’t compare, and that’s why, if you take just one piece of advice away from your childhood, make it this one: eat your broccoli!5 Leading Benefits of BroccoliWe’ve compiled an extensive review of the health benefits of broccoli on our Broccoli Food Facts page. This cruciferous veggie (in the same family as Brussels sprouts, cabbage, cauliflower, and more) is one of the best health-boosting foods around, with research proving its effectiveness for …1. ArthritisRecent tests on cells, tissues and mice show that a sulfur-rich broccoli compound, sulforaphane, blocks a key destructive enzyme that damages cartilage.1 It’s thought that increasing broccoli in your diet may help to slow down and even prevent osteoarthritis.2. CancerSulforaphane in broccoli has also been shown to kill cancer stem cells, thereby striking to the root of tumor growth, and the broccoli compound glucoraphanin -- a precursor to sulforaphane – boosts cell enzymes that protect against molecular damage from cancer-causing chemicals.2, 3Studies have also found that sulforaphane normalizes DNA methylation4 —a process that involves a methyl group (one carbon atom attached to three hydrogen atoms) being added to part of a DNA molecule, and therefore influencing its expression.DNA methylation is a crucial part of normal cell function, allowing cells to "remember who they are and where they have been" and is indispensable for regulating gene expression.DNA methylation also suppresses the genes for things you don’t want, such as viral and other disease-related genes, and abnormal DNA methylation plays a critical role in the development of nearly all types of cancer.One study published in PLoS One,5 for instance, found that just four servings of broccoli per week could protect men from prostate cancer. One serving of broccoli is about two spears, so that's only 10 broccoli spears per week.In this study, the researchers collected tissue samples over the course of the study and found that the men who ate broccoli showed hundreds of beneficial changes in genes known to play a role in fighting cancer.3. Blood Pressure and Kidney HealthSulforaphane in broccoli may also significantly improve your blood pressure and kidney function, according to yet another study in which hypertensive rats with impaired kidney function were given sulforaphane. The natural compound improved the rats' kidney function and lowered their blood pressure by normalizing DNA methylation patterns within their cells.64. Anti-Aging and Immune System HealthSulforaphane also seems to stimulate a variety of antioxidant defense pathways in your body that can directly reduce oxidative stress and slow down the decline in your immune system that happens with age.7 In theory, this means that eating vegetables that contain sulforaphane, such as broccoli, could quite literally slow down the hands of time.5. Heart Health, Especially for DiabeticsSulforaphane encourages production of enzymes that protect the blood vessels, and reduces the number of molecules that cause cell damage -- known as Reactive Oxygen Species (ROS) -- by up to 73 percent.8 People with diabetes are up to five times more likely to develop cardiovascular diseases such as heart attacks and strokes -- both of which are linked to damaged blood vessels. Eating broccoli may help to reverse some of this damage.Broccoli Benefits Your Eyes, Your Skin and Much MoreThe benefits of broccoli are seemingly endless. It’s also known, for instance, that broccoli:9Supports your body’s detoxification, thanks to the phytonutrients glucoraphanin, gluconasturtiian, and glucobrassicinIs anti-inflammatory (inflammation is at the root of many chronic diseases)Contains the flavonoid kaempferol, wh[...]



Effects of age on male fertility.

2013-09-24T09:38:18.231-07:00

Best Pract Res Clin Endocrinol Metab. 2013 Aug;27(4):617-28. doi: 10.1016/j.beem.2013.07.004. Epub 2013 Aug 17.
Effects of age on male fertility.
Source
Centre for Reproductive Medicine and Andrology/Clinical Andrology, Domagkstrasse 11, D-48149 Muenster, Germany. Electronic address: Michael.Zitzmann@ukmuenster.de.
Abstract
Later parenting is considered by many to have advantages, parents-to-be may feel themselves more stable to rear children. In addition, many men start a second family later in life. Thus, paternal age becomes an emerging issue. Aging affects male fertility by a scope of factors, which are not fully understood to date. Generally, the amount of produced sperm cells as well as their motility decreases with age, as testicular histological architecture deteriorates. Decreased fecundity and an increased risk for disturbed pregnancies occur with advancing paternal age. Some rare autosomal dominant pathologies are clearly related to paternal age. Altered patterns of epigenetics/gene expression in aging sperm seem to affect a range of neurocognitive disorders and also metabolic dyshomeostasis across generations. Such effects refer to men older than 40 years and may have impact on socio-economic issues. Nevertheless, councelling of older men seeking paternity should be patient-oriented and weigh statistical probabilities against the right for individual life-planning.
Copyright © 2013 Elsevier Ltd. All rights reserved.
KEYWORDS:

aging and sperm, aging fathers, epigenetics and fertility, male fertility, paternal age



New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.

2013-06-07T07:27:22.222-07:00

Hum Mol Genet. 2013 Jun 4. [Epub ahead of print]
New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.
Source
Molecular and Computational Biology Program, University of Southern California, Los Angeles 90089, California, United States of America.
Abstract
There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age-effect. The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false positive rate lower than 2.7x10-6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism.

PMID: 23740942 [PubMed - as supplied by publisher]



Common Genetic Disease Linked to Father’s Age

2013-06-06T16:32:20.229-07:00

Common Genetic Disease Linked to Father’s Age
1 hour ago

Genetic mutation of a testis stem cell actually gives the disease an edge, making older fathers more likely to pass it along to their children
Scientists at USC have unlocked the mystery of why new cases of the genetic disease Noonan Syndrome are so common: a mutation that causes the disease disproportionately increases a normal father’s production of sperm carrying the disease trait. 
When this Noonan syndrome mutation arises in a normal sperm stem cell it makes that cell more likely to reproduce itself than stem cells lacking the mutation. The father then is more likely to have an affected child because more mutant stem cells result in more mutant sperm. The longer the man waits to have children the greater the chance of having a child with Noonan syndrome.
Noonan Syndrome is among the most common genetic diseases with a simple inheritance pattern. About one of every 4,000 live births is a child with a new disease mutation. The disease can cause craniofacial abnormalities, short stature, heart defects, intellectual disability and sometimes blood cancers.
By examining the testes from 15 unaffected men, a team led by USC molecular and computational biologists Norman Arnheim and Peter Calabrese found that the new mutations were highly clustered in the testis, and that the overall proportion of mutated stem cells increased with age. Their computational analysis indicated that the mutation gave a selective edge over non-mutated cells.
“There is competition between stem cells with and without the mutation in each individual testis,” said Arnheim, who has joint appointments at the USC Dornsife College of Letters, Arts and Sciences and the Keck School of Medicine of USC. “But what is also unusual in this case is that the mutation which confers the advantage to testis stem cells is disadvantageous to any offspring that inherits it.”
The new findings also suggest an important new molecular mechanism to explain how certain genetic disease mutations can alter sperm stem cell function leading to exceptionally high frequencies of new cases every generation.
The Arnheim and Calabrese team included USC postdoctoral research associates Song-Ro Yoon, and Soo-Kung Choi, graduate student Jordan Eboreime and Dr. Bruce D. Gelb of the Icahn School of Medicine at Mount Sinai in New York City. A paper detailing their research will be published on June 6 in The American Journal of Human Genetics.
This research was supported by the National Institute of General Medical Sciences grant number R01GM36745 and the National Heart, Lung and Blood Institute (National Institutes of Health) grant number HL071207.
###

Contact: Robert Perkins at (213) 740-9226 or perkinsr@usc.edu



. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age.

2013-05-21T19:53:08.814-07:00


Trends Genet. 2013 May 16. pii: S0168-9525(13)00070-X. doi: 10.1016/j.tig.2013.04.005. [Epub ahead of print]
Properties and rates of germline mutations in humans.
Source
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Abstract
All genetic variation arises via new mutations; therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. However, advances in sequencing technology have allowed for empirical assessments of genome-wide rates of mutation. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age. Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). Here, we review the genome-wide analyses for the mutation rate of several types of variants and suggest areas for future research.
Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID: 23684843 [PubMed - as supplied by publisher]



Impact of age on male fertility.

2013-03-16T06:47:34.885-07:00


2013 Mar 13. [Epub ahead of print]

Impact of age on male fertility.

Source

University of Tennessee Graduate School of Medicine, Knoxville, Tennessee, USA.

Abstract

PURPOSE OF REVIEW:

An increasing number of older men are seeking help for fathering a child, but male fertility gradually declines with age. This review highlights changes in male reproductive biology and practical clinical concerns for aging men.

RECENT FINDINGS:

Aging may have an impact on sperm DNA damage such as single nucleotide polymorphisms. A recent landmark study identified that the number of single gene de-novo mutations in the offspring increased by two mutations per year based on paternal age. Additionally, advanced paternal age has been linked with neurocognitive disorders such as autism and schizophrenia. For the management of hypogonadism, strategies using selective estrogen modulators have been increasingly utilized to maintain fertility potential.

SUMMARY:

Aging has an impact on male fertility potential, as well as potential genetic effects for the offspring.



Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

2012-09-11T17:37:12.055-07:00

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: ArubaObjectiveThe aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.DesignA case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.ResultsAdvanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.ConclusionThis study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.ArticleMetricsRelated ContentComments: 0To add a note, highlight some text. Hide notesMake a general commentJump toAbstractIntroductionMethodsResultsDiscussionConclusionAcknowledgmentsAuthor ContributionsReferencesIngrid D. C. van Balkom1,2,3*, Michaeline Bresnahan4,5, Pieter Jelle Vuijk6, Jan Hubert7, Ezra Susser4,5,8, Hans W. Hoek4,9,101 Child and Adolescent Psychiatry Clinic, Oranjestad, Aruba, 2 Jonx Department of Youth Mental Health, Lentis Psychiatric Institute, Groningen, The Netherlands, 3 Rob Giel Research Center, Department of Psychiatry, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands, 4 Mailman School of Public Health, Columbia University, New York, New York, United States of America, 5 New York State Psychiatric Institute, New York, New York, United States of America, 6 Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands, 7 Child and Youth Health Services, Department of Public Health of Aruba, Oranjestad, Aruba, 8 College of Physicians and Surgeons of Columbia University, New York, New York, United States of America, 9 Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands, 10 Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsAbstract TopObjectiveThe aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.DesignA case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.ResultsAdvanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.ConclusionThis study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.Citation: van Balkom IDC, Bresnahan M, Vuijk PJ, Hubert J, Susser E, et al. (2012) Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba. PLoS ONE 7(9): e45090. doi:10.1371/journal.pone.0045090Editor: Thomas Burne, University of Queensland, Australia Received: March 9, 2012; [...]






Rate of de novo mutations and the importance of father's age to disease risk. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Jonasdottir A, Wong WS, Sigurdsson G, Walters GB, Steinberg S, Helgason H, Thorleifsson G, Gudbjartsson DF, Helgason A, Magnusson OT, Thorsteinsdottir U, Stefansson K. Nature. 2012 Aug 22;488(7412):471-5. doi: 10.1038/nature11396. PMID: 22914163 [PubMed - in process]

2012-08-24T08:12:13.457-07:00

Rate of de novo mutations and the importance of father's age to disease risk. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Jonasdottir A, Wong WS, Sigurdsson G, Walters GB, Steinberg S, Helgason H, Thorleifsson G, Gudbjartsson DF, Helgason A, Magnusson OT, Thorsteinsdottir U, Stefansson K. Nature. 2012 Aug 22;488(7412):471-5. doi: 10.1038/nature11396. PMID: 22914163 [PubMed - in process]



http://www.nytimes.com/2012/08/23/health/fathers-age-is-linked-to-risk-of-autism-and-schizophrenia.html?_r=1&emc=na

2012-08-22T17:29:01.417-07:00

http://www.nytimes.com/2012/08/23/health/fathers-age-is-linked-to-risk-of-autism-and-schizophrenia.html?_r=1&emc=na






The Effect of Paternal Age on Fetal Birth Outcomes.

2012-05-09T08:24:11.157-07:00


Am J Mens Health. 2012 May 7. [Epub ahead of print]

The Effect of Paternal Age on Fetal Birth Outcomes.

Abstract

Research investigating the role of paternal age in adverse birth outcomes is limited. This population-based retrospective cohort study used the Missouri maternally linked data set from 1989 to 2005 to assess whether paternal age affects fetal birth outcomes: low birth weight (LBW), preterm birth (PTB), stillbirth, and small size for gestational age (SGA). We examined these outcomes among infants across seven paternal age-groups (<20, 20-24, 25-29, 30-34, 35-39, 40-45, and >45 years) using the generalized estimating equation framework. Compared with infants born to younger fathers (25-29 years), infants born to fathers aged 40 to 45 years had a 24% increased risk of stillbirth but a reduced risk of SGA. A 48% increased risk of late stillbirth was observed in infants born to advanced paternal age (>45 years). Moreover, advanced paternal age (>45 years) was observed to result in a 19%, 13%, and 29% greater risk for LBW, PTB, and VPTB (very preterm birth) infants, respectively. Infants born to fathers aged 30 to 39 years had a lower risk of LBW, PTB, and SGA, whereas those born to fathers aged 24 years or younger had an elevated likelihood of experiencing these same adverse outcomes. These findings demonstrate that paternal age influences birth outcomes and warrants further investigation.
PMID:
22564913
[PubMed - as supplied by publisher] 



Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner

2012-05-01T07:53:34.656-07:00

Neuron. 2012 Apr 26;74(2):285-99.De novo gene disruptions in children on the autistic spectrum.Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR, Wigler M.SourceCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.AbstractExome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.Copyright © 2012 Elsevier Inc. All rights reserved. PMID:22542183 [PubMed - in process] [...]



Clues To Autism: Genetic Mutations And The Age Of The Father

2012-04-06T20:10:04.767-07:00

Clues To Autism: Genetic Mutations And The Age Of The Father



Fertility clock ticks for men, too

2012-03-25T09:12:18.101-07:00

Fertility clock ticks for men, too

Julia Medew March 26, 2012






MEN are being urged to pay more attention to their biological clocks as research shows those aged over 40 are at higher risk of having a child with autism and birth defects.

As the average age of Australian fathers continues to increase, reproductive health experts are calling for men to learn more about their fertility and the risks of older fatherhood.

Dr Karin Hammarberg, a researcher with the Victorian Assisted Reproductive Treatment Authority (VARTA), said that while most children are born healthy, large studies of parental age were starting to show higher rates of birth defects and autism in children born to men over 40.

A recent review of paternal age published in the Asian Journal of Andrology said an American study of 132,000 men found children of those over 45 were nearly six times more likely to have an autism spectrum disorder compared to children born to men under 30.

The review also pointed to a Dutch study of 60,000 births which found children born to men over 40 were three times more likely to have autism and a US study of 5 million births which showed men over 50 had a 15 per cent higher chance of having a baby with birth defects including congenital heart disease and cleft palates.

Dr Hammarberg said research also showed men over 40 had much more trouble getting a woman pregnant and the rate of miscarriage doubled for women when their partner was over 45. The average time to pregnancy for men under 25 is just over 4.5 months but nearly two years for men over 40.

"Fertility talk is always directed at women and somehow men look like innocent bystanders," she said.

"Men really need to know that their own age and health will affect their fertility, too."

Between 1990 and 2010, the median age of Australian fathers increased from 31 to 34 while more men in their late 50s and early 60s were becoming fathers. In 2010, 777 men aged 55 to 59 fathered a child, up from 674 in 2004 and 516 in 2000. The number of men in their 60s having babies has also increased from 226 in 2000 to 408 in 2010.

The Fertility Coalition, made up of VARTA, Andrology Australia, Jean Hailes for Women's Health and the Robinson Institute, will launch a website today to teach Australians about fertility. See yourfertility.org.au



Advanced paternal age increases the risk of schizophrenia and obsessive-compulsive disorder in a Chinese Han population.

2012-03-20T08:06:59.889-07:00

Psychiatry Res. 2012 Mar 16. [Epub ahead of print]

Advanced paternal age increases the risk of schizophrenia and obsessive-compulsive disorder in a Chinese Han population.

Wu Y, Liu X, Luo H, Deng W, Zhao G, Wang Q, Zhang L, Ma X, Liu X, Murray RA, Collier DA, Li T.


Source

The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.


Abstract

Using the Structured Clinical Interview for DSM-IV, patient and non-patient version (SCID-P/NP), this study investigated 351 patients with schizophrenia, 122 with obsessive-compulsive disorder (OCD), and 238 unrelated healthy volunteers in a Chinese Han population. The relative risks effected by advanced paternal age for schizophrenia and OCD in offspring were computed under logistic regression analyses and adjusted for the participant's sex, age and co-parent age at birth. Compared to the offspring with paternal age of 25-29years old, the relative risks rose from 2.660 to 10.183 in paternal age range of 30-34 and ≥35. The relative risks for OCD increased from 2.225 to 5.413 in 30-34 and ≥35. For offspring with paternal age of <25, the odds ratios of developing schizophrenia and OCD were 0.628 and 0.289 respectively, whereas, an association between increased maternal age and risk for schizophrenia/OCD was not seen. Interaction analysis showed an interaction effect between paternal age and maternal age at birth. Such a tendency of risk affected by parental age for schizophrenia and OCD existed after splitting out the data of early onset patients. Sex-specific analyses found that the relative risks for schizophrenia with paternal age of 30-34 and ≥35 in male offspring were 2.407 and 10.893, in female were 3.080 and 9.659. The relative risks for OCD with paternal age of 30-34 and ≥35 in male offspring were 3.493 and 7.373, and in female offspring 2.005 and 4.404. The mean paternal age of schizophrenia/OCD patients born before the early 1980s was much greater than that of patients who were born after then. The findings illustrated that advanced paternal age is associated with increased risk for both schizophrenia and OCD in a Chinese Han population, prominently when paternal age is over 35. Biological and non-biological mechanisms may both be involved in the effects of advanced paternal age on schizophrenia and OCD.

Copyright © 2012. Published by Elsevier Ireland Ltd.



Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.

2012-02-14T09:01:39.037-08:00

Am J Hum Genet. 2012 Feb 10;90(2):175-200.

Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.

Goriely A, Wilkie AO.


Source

Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.


Abstract

Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition.

Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.


PMID: 22325359 [PubMed - in process]



James Crow Dies

2012-01-11T10:13:08.328-08:00

James Crow Dies

January 11, 2012




James Crow, who was a population geneticist at the University of Wisconsin-Madison, has died, reports The New York Times. He was 95. Crow studied mutational load, and was part of on a National Academy of Sciences committee that assessed mutational damage to the populations of Hiroshima and Nagasaki following the use of atomic bombs there. He also was on a committee that paved the way for using DNA forensics in court. The Times notes that when Crow began teaching in the 1940s and 1950s, the field of genetics underwent rapid changes. "When anxious students asked Dr. Crow what would be in the exams, he would tell them that the questions were the same every year but that the answers were different," the Times says.



Neuron. 2011 Dec 22;72(6):951-63. High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

2012-01-07T09:41:41.161-08:00

Neuron. 2011 Dec 22;72(6):951-63.

High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

Malhotra D, McCarthy S, Michaelson JJ, Vacic V, Burdick KE, Yoon S, Cichon S, Corvin A, Gary S, Gershon ES, Gill M, Karayiorgou M, Kelsoe JR, Krastoshevsky O, Krause V, Leibenluft E, Levy DL, Makarov V, Bhandari A, Malhotra AK, McMahon FJ, Nöthen MM, Potash JB, Rietschel M, Schulze TG, Sebat J.


Source

Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 12824, USA.


Abstract

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

Copyright © 2011 Elsevier Inc. All rights reserved.



The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years

2012-01-04T08:48:55.645-08:00

Encephale. 2011 Jun;37(3):199-206. Epub 2011 Apr 2.[Influence of paternal age in schizophrenia]. [Article in French]Hubert A, Szöke A, Leboyer M, Schürhoff F.SourcePôle de psychiatrie du CHU de Créteil, groupe hospitalier Henri-Mondor-Albert-Chenevier, AP-HP, 40, rue Mesly, 94000 Créteil, France.AbstractBACKGROUND: Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations.METHODS: All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009.RESULTS: After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis.DISCUSSION: The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal popu[...]



Advancing paternal age and simplex autism.

2011-12-20T08:40:48.568-08:00

Autism. 2011 Dec 16. [Epub ahead of print]

Advancing paternal age and simplex autism.

Puleo CM, Schmeidler J, Reichenberg A, Kolevzon A, Soorya LV, Buxbaum JD, Silverman JM.


Source

Temple University, Philadelphia, PA, USA.


Abstract

De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors



Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men

2011-11-02T14:55:58.372-07:00

Andrologia. 2011 Nov 1. doi: 10.1111/j.1439-0272.2011.01243.x. [Epub ahead of print]
Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men.
Varshini J, Srinag BS, Kalthur G, Krishnamurthy H, Kumar P, Rao SB, Adiga SK.
Source Clinical Embryology, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, India  National Centre for Biological Sciences, Tata Institute for Fundamental Research UAS-GKVK Campus, Bangalore, India  Department of Radiation Biology and Toxicology, Manipal Life Science Centre, Manipal University, Manipal, India.

Abstract
With increasing evidence for faulty paternal contribution to reproduction, there has been a steady increase in studies highlighting an association between sperm DNA damage, failed/delayed fertilisation and aberrant embryo development. Owing to prevailing ambiguity, the aims of the study were to analyse the genetic integrity of the male gamete and then to understand its association with age, standard semen parameters, lifestyle and occupational factors. The study included 504 subjects, attending university infertility clinic for fertility evaluation and treatment. Semen characteristics were analysed by standard criteria; terminal deoxynucelotidyl transferase-mediated nick end-labelling assay was employed for DNA damage assessment. The average incidence of sperm DNA damage in patients with normozoospermic semen parameters was <10%. Patients with oligozoospermia, severe oligozoospermia, oligoasthenoteratospermia, asthenoteratozoospermia and necrozoospermia had significantly higher level of sperm DNA damage (P < 0.001). Patients above 40 years of age had significantly high levels of DNA damage (P < 0.001) compared with their counterparts. Patients with varicocele and a history of alcohol consumption had higher incidence of spermatozoa with DNA damage (P < 0.01). Poor sperm characteristics in the ejaculate are associated with increased sperm DNA damage. Age-related increase in sperm DNA damage and association of the same with varicocele and alcohol consumption are also demonstrated.

© 2011 Blackwell Verlag GmbH.

PMID:22040161[PubMed - as supplied by publisher]



Advanced paternal and grandpaternal age and schizophrenia

2011-10-18T08:24:16.420-07:00

Schizophr Res. 2011 Oct 13. [Epub ahead of print]
Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective.
Frans EM, McGrath JJ, Sandin S, Lichtenstein P, Reichenberg A, Långström N, Hultman CM.
SourceDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract
BACKGROUND: Advanced paternal age has been linked with an increased risk of schizophrenia in the offspring. If age-related de novo mutations in the male germ line underlie this association, grandpaternal and paternal age would both be expected to influence the risk of schizophrenia. The aim of the current study was to explore the links between both paternal and grandpaternal age with respect to the risk of schizophrenia in a large, national register-based cohort.

METHOD: We linked the Swedish Multi-Generation and Hospital Discharge Registers and compared parents' ages at offspring birth for 20,582 schizophrenia-affected and 100,176 non-affected individuals. Grandparents' ages at the birth of the parent were compared between 2511 affected and 15,619 non-affected individuals. The risk of schizophrenia was examined with logistic regression when the predictor variable (parent or grandparent age) varied across age strata.

RESULTS: After adjusting for maternal age, birth year and proband sex, we confirmed that offspring of older fathers had an increased risk of schizophrenia. Compared to those with paternal age 20-24years, those with fathers >55years had a two-fold increased risk of schizophrenia. With respect to grandparent age, older maternal (but not paternal) grandfather age was associated with an increased risk of schizophrenia. Compared to maternal grandfather age 20-24years, those with maternal grandfathers >55years had a significantly increased risk of schizophrenia (adjusted odds ratio and 95% confidence intervals; 2.79, 1.71-4.56). The pattern of results was essentially unchanged when we examined male and female probands separately.

CONCLUSION: This is the first study to report an association between grandpaternal age and risk of schizophrenia. The selective effect of advanced maternal grandfather age suggests that the biological mechanisms involving the X-chromosome may differentially contribute to the association between paternal age and offspring risk of schizophrenia.

Copyright © 2011. Published by Elsevier B.V.



De novo copy number variants associated with intellectual disability have a paternal origin and age bias.

2011-10-05T08:45:27.203-07:00

Med Genet. 2011 Oct 3. [Epub ahead of print]
De novo copy number variants associated with intellectual disability have a paternal origin and age bias.
Hehir-Kwa JY, Rodríguez-Santiago B, Vissers LE, de Leeuw N, Pfundt R, Buitelaar JK, Pérez-Jurado LA, Veltman JA.
Source1Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract
BackgroundDe novo mutations and structural rearrangements are a common cause of intellectual disability (ID) and other disorders with reduced or null reproductive fitness. Insight into the genomic and environmental factors predisposing to the generation of these de novo events is therefore of significant clinical importance.MethodsThis study used information from single nucleotide polymorphism microarrays to determine the parent-of-origin of 118 rare de novo copy number variations (CNVs) detected in a cohort of 3443 patients with ID.ResultsThe large majority of these CNVs (76%, p=1.14×10(-8)) originated on the paternal allele. This paternal bias was independent of CNV length and CNV type. Interestingly, the paternal bias was less pronounced for CNVs flanked by segmental duplications (64%), suggesting that molecular mechanisms involved in the formation of rare de novo CNVs may be dependent on the parent-of-origin. In addition, a significantly increased paternal age was only observed for those CNVs which were not flanked by segmental duplications (p=0.02).ConclusionThis indicates that rare de novo CNVs are increasingly being generated with advanced paternal age by replication based mechanisms during spermatogenesis.

PMID:21969336[PubMed - as supplied by publisher]