Biological clock ticks for dads too

Biological clock ticks for dads too
Grant McArthur
June 03, 2008 12:00am

CHILDREN born to older fathers are almost twice as likely to die before adulthood than those born to younger men, research shows.
Increased rates of birth defects, autism, schizophrenia, epilepsy and heart disease are believed to make children born to dads over 45 much less likely to live to 19 than those with fathers in their late 20s.
A Danish study of more than 100,000 children raises the prospect that biological clocks are ticking for men as sperm quality deteriorates with age.
Children born to teen fathers and over-45s are up to 88 per cent more likely to die before their 19th birthday than those born to men aged 25-29, researchers from the University of Aarhus found.
While deaths of children fathered by teens could be explained by their mothers also being young and often disadvantaged, the older men's children were only affected by their fathers' "underlying biological causes".
"The risks of older fatherhood can be very profound and it is not something that people are always aware of," said study author Jin Liang Zhu, from the Danish Epidemiology Science Centre.
The research, which tracked the children for up to the first 18 years, was published in the European Journal of Epidemiology.
Of 831 deaths, 601 were in the first year. Many were due to congenital defects.
Clinical geneticist Les Sheffield, of Melbourne's Murdoch Childrens Research Institute, said it was time fathers took responsibility for the risks.
Assoc Prof Sheffield said genetic errors in sperm increase by half a per cent when a man reaches 40, by 2 per cent when he is 50, by 5 per cent when he is 60 and by 20 per cent by the time he is 80.
"Men around 40 ought to be thinking about the increased risk to their children, the same as women do," he said.
"I speak to a lot of older parents and they talk about the women's risk, but when I talk about the father's risk they are just aghast because nobody has ever mentioned the father before," he said

A CAUSE OF AUTISM UNVIELED OLDER FATHERS! Priest Bans Autistic Boy From Church

Average Paternal Age is Very High and In the Danger Zone for Offspring

Average paternal age is very high. Fewer men are fathering babies in their 20s when risk for NEW genetic disorders due to sperm is very low. By 35 men are in the danger zone for having autistic, schizophrenic, Alzheimer's, cancer prone offspring. The numbers of offspring with neurodevelopmental disorders is rising along with the rise in average pateral age. What to do since no one warns the public. Any suggestions would be helpful. Also any ideas as to why, in 1994 the definition of autism was broadened from classical autism.

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Are there 'risks' in being an older father?
Whilst the average age of fathering a child is 32, recent figures from the UK's Office for National Statistics show that in 2004 more than 75,000 babies were born to fathers aged 40 and over - more than one in ten of all children born. Further, around 6,489 children a year are born to fathers aged fifty-plus.
According to US-based National Center for Health Statistics, in 2004 about 24 in every 1000 men aged 40 - 44 fathered a child. This is up almost 18% from a decade ago. Meanwhile, only 3 out of every 1,000 men aged 55 and older are fathers to live births.
Whilst the topic of "older fathers" is increasingly making headlines, what is perhaps less well-known is that there can be risks - both physical and mental - associated with fathering offspring later in life.
Recent research revealed that compared to younger dads, fathers in the older age group were more inclined to be less tolerant of their children's physical activities, perceiving them to be more impulsive and overactive. Older dads apparently also show less affection and warmth towards their partner. [Read about this study]
Risk of autism in children born to older dads
A study recently published in the Archives of General Psychiatry concludes that the offspring of older fathers have a significantly increased risk of autism. The team of UK and US researchers said that children born to men over 40 had a six times higher risk than those born to men under 30. They also said the study was further proof men also had "biological clocks".
The mother's age did not appear to influence the chances a child would have autism, although previous studies into this have produced mixed results.
Rare birth disorders and schizophrenia
The incidences of certain rare birth disorders, such as Dwarfism, or achondroplasia (a genetic disorder that affects bone growth and is the most common growth-related birth defect. It occurs in about one in every 25,000 births, affects all races, both males and females and limits their growth to about four feet), are more common amongst births to older fathers. Some of these defects, thought to be new mutations, are only detectable later in life, e.g. schizophrenia.
Researchers at Columbia University College of Physicians and Surgeons found that men aged 50 or over are three times more likely to father a child with schizophrenia compared to men of 25 or under, and men aged between 45 and 49 are twice as likely to have a child with the illness. The researchers estimated that as many as one in four cases of schizophrenia may be caused by the father being old.
The study, published in the Archives of General Psychiatry, looked at records of almost 88,000 people born in Jerusalem between 1964 and 1976, and compared them to data from the Israel Psychiatric Register (part of the Israeli Ministry of Health).
Apert syndrome, which afflicts one in every 70,000 children who are born with fused bones in their heads, hands, and feet, is also linked to the father's age. Men in their 50s and 60s are 10 times as likely to carry and pass along the mutation as men under 30.
Pre-term birth
A study published in the March 2005 issue of Epidemiology, revealed that the risk of preterm birth increases with paternal age. The authors studied couples and their first children, using nationwide registers in Denmark between 1980 and 1996.
Genetic abnormalities & limb defects
Because of the increased risk of genetic abnormalities in the offspring of older fathers, The American Society for Reproductive Medicine has set an upper age limit of 40 years old for semen donors, whilst UK fertility clinics only accept sperm donations from men aged 39 and under.
Research published in November 2005, reveals that men aged 50 and above were more than four times more likely to have a child with Down syndrome and that older men are more likely to have babies with a variety of limb defects. Epidemiologist, Dr Jorn Olsen and his team from the University of California, Los Angeles, used the Danish Fertility Database, which holds information on 70,000 couples and their first born child, to look for differences in children with older fathers.
The finding caused concern among some fertility specialists, who saw the age of sperm donors increase with the government's abolition of sperm donor anonymity earlier this year. "With the change in the law, donors tend to be men who have already had their families," said Allan Pacey, a fertility expert at Sheffield University.
"But about a third of all births in the UK are from men who are older than 35 and, frankly, that's not the best sperm to use in fertility treatment. You want sperm from young, healthy guys that hasn't had time to build up defects."
Dr Olsen reported to New Scientist magazine that whilst the medical risks of starting families older are smaller for older fathers than for women approaching the menopause, the trend of couples starting families later in life means the issue of male age should be taken into consideration.
Research shows that old fathers are three times more likely to take regular responsibility for a young child.
Jack O'Sullivan, Fathers Direct
Sperm quality deteriorates
A study published in June 2006 by Dr Andrew Wyrobek, of the Lawrence Livermore National Laboratory in Livermore, California, found that the genetic quality of sperm deteriorates as a man gets older, becoming steadily more fragmented the older a man gets. DNA fragmentation is associated with greater infertility and a reduction in the chance of conceiving.
Each successive fragmentation introduces a slight risk of error in the genetic material of the new sperm, and this is then passed on to the child. These mutations are tiny and difficult to spot without knowing what mutations to look for. Abnormalities in women's eggs can be picked up more easily, as almost all divisions in a woman's eggs occur before she is born.
Dr Brenda Eskenazi, a co-author of the report, said: "Our research suggests that men, too, have a biological time clock - only it is different. Men seem to have a gradual, rather than an abrupt change in fertility and in the potential ability to produce viable, healthy offspring."
The study included at least 15 men from each age decade spanning 20 to 60 years, and 25 aged 60 to 80. Smokers and men who had fertility problems, or a history of cancer were excluded.
Higher risk of miscarriage
Research published in August 2006 suggests that women who become pregnant by older men are at far greater risk of having a miscarriage. The researchers, from the Columbia University School of Public Health in New York and led by Dr. Karine Kleinhaus, noted that the risk of miscarriage appeared to rise along with the father's age, regardless of how old the mother was. Even after a range of other risk factors which contribute to miscarriage were taken into account, such as smoking during pregnancy and maternal diabetes, the risk was still higher.
The study's authors analysed data from a survey of nearly 14,000 pregnant women undertaken in Jerusalem between 1964 and 1976. 1,500 of those women suffered miscarriages, whilst 12,000 carried their babies to term. The findings were reported in the Journal of Obstetrics & Gynecology.
The risk of losing a baby was 60 per cent higher when the father was aged 40 or over, compared to when he was 25 to 29 years old. It was also about three times greater when the man was aged between 35 and 39 years of age, than if he were younger than 25.
Dr Kleinhaus commented, "As child-bearing is increasingly delayed in Western societies, this study provides important information for people who are planning their families." However, researchers pointed out that despite this generally higher miscarriage rate, older paternal age may only slightly raise the risk to any one couple.
Longer to conceive
A study reported on in July 2000 in Human Reproduction and based on research carried out by teams at Bristol and Brunel universities in the UK, discovered that the older a man is the longer it may take his partner to conceive, regardless of her age. Women with partners five or more years older have less chance of conceiving within a year of trying than those whose partners are the same age, or younger. The odds of conceiving within 6 months of trying decrease by 2% for every year that the man is older than 24 years, and for conception within a year decrease by 3% for each year.
Lower Apgar score
A study published in the July 2006 issue of Epidemiology indicates that new fathers in their 40s and 50s are slightly more likely to have an infant with a low Apgar score than fathers in their 20s. The Apgar score, which was first created in 1952, rates the newborn on five parameters: respiratory effort, heart rate, reflex irritability, muscle tone, and skin color with a value of 0 to 2 (worst to best) for each. Thus, a total score of 10 is optimal. The score is calculated at 1 and 5 minutes after birth.
Statistics on older fathers
Since 1980, there has been about a 40 per cent increase in the number of men between 35 and 50 fathering children and a 20 per cent decrease in the number of fathers under 30. Data from the UK's Office For National Statistics (ONS) reveals that in 1971 the mean age of a father at birth was 27.2 years, but by 1999 this had risen to 30.1. Statistics from 1997 show that whilst the majority of fathers (151,162) were in the 30-34 age group, there were 41,459 fathers aged 40 to 65+ years.
Average age of fathers in Australia now 32.9 years
Australian fathers were an average of 32.9 years old - 2.8 years older than dads with newborns in 1985.

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consequences of autism


Priest Bans Autistic Boy From Church
Mom Told She'd Be Sent to Jail if She Brought Autistic Son to Church
BERTHA, Minn.
May 19, 2008
A Catholic priest has filed a restraining order against the parents of a severely autistic 13-year-old boy in an effort to keep him from attending the church in Bertha on Sundays.

Priest files restraining order against parents with "unruly" autistic 13-yr-old.The Rev. Daniel Walz alleges that Adam Race's unruly behavior endangers others who attend the Church of St. Joseph.

Race's parents have ignored the restraining order, calling it discriminatory, and Carol Race, Adam's mother, was cited by police and is due to appear in court on Monday for violating the order.

"He said that we did not discipline our son. He said that our son was physically out of control and a danger to everyone at church," Carol Race said. "I can't discipline him out of his autism, and I think that's what our priest is expecting."

Carol Race said it all started last June, when Walz and a church trustee visited the Races at their home address the behavior of Adam, who stands taller than six feet and weighs more than 225 pounds.

Related
Answers to Autism May Be Inside the BrainWATCH: New Method for Autism DiagnosisSend Dr. Miranda Your Autism QuestionsIn an affidavit, Walz said the church "explored and offered many options for accommodations that would assist the family while protecting the safety of parishioners. The family refused those offers of accommodation."

Carol Race said the family of seven, which has attended St. Joseph since 1996, typically sat in the cry room or in the back pew to keep avoid disrupting the services and did not hear a complaint from the parishioners until Walz showed up at their home in June.


Even after the restraining order was served, the family continued going to the church and would leave during the closing hymn to avoid contact with others, Carol Race said.

The Diocese of St. Cloud issued a statement saying the petition was filed "as a last resort out of a growing concern for the safety of parishioners and other community members due to disruptive and violent behavior on the part of that child."

Walz said the boy's behavior worsened over time, telling authorities that Adam has been "extremely disruptive and dangerous" since last summer.

According to Walz, Adam struck a child during mass, nearly knocks elderly parishioners over when he hastily exits the church, spits and sometimes urinates in church and fights when he is being restrained.

Do Copy Number Variations Increase With Older Paternal Age, Is That Why Non-Familial Cancers, Autism, Schizophrenia, Autoimmune Diseases Increase

Canadian, British And American Scientists Launch Major New Genome Partnership To Catalogue All Common Copy Number Variations
Main Category: Genetics News


An international team will use state-of-the-art, high-density microarrays and new computer algorithms to improve the detection of variants in the human genome which are implicated in various diseases. The new systems are the foundation of Phase 2 of the Genome Structural Variation Consortium, which was set up in 2004 and seeks to identify structurally variable regions in the human genome.

In 2006, the Genome Structural Variation Consortium, along with other international collaborators, generated a first-generation map of copy number variants (CNVs) covering the human genome. The CNVs that they identified, which in many cases lead to deletion or duplication of genes along chromosomes, tended to encompass large stretches of DNA ranging from thousands to millions of chemical bases of DNA. These changes are part of the normal variability between apparently healthy people, but some may also predispose individuals to disease. The data also suggested that thousands more CNVs exist, but technological limitations associated with that earlier study precluded the discovery of more CNVs.

The new comprehensive map will be critical for studies attempting to identify genes involved in both rare and common diseases. "Our experiments will generate the highest-resolution CNV catalogue of worldwide populations. The initiative will also complement ours, and other efforts to sequence entire genomes", said Dr. Stephen Scherer, Senior Scientist and Director, The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children (SickKids) in Toronto.

In its second phase, this international research collaboration will develop a comprehensive, higher resolution CNV map for the Human Genome - at a level 100-fold finer than the first map. Working with NimbleGen Systems, Inc. of Madison, Wisconsin, USA, the Consortium has designed a novel set of 2.1-million-feature microarrays that will enable genome-wide detection of CNVs with 42 million probes. The set of microarrays have been referred to as "whole-genome oligonucleotide tiling arrays" because they cover almost all DNA along chromosomes, spaced at intervals of only 50 bases, or letters of DNA code.

The international consortium is led by Scherer, Drs. Nigel Carter, Matthew Hurles, and Chris Tyler-Smith of the Wellcome Trust Sanger Institute, and Dr. Charles Lee from Brigham and Women's Hospital and Harvard Medical School.

To better understand CNVs and diseases, researchers and clinicians around the world are now accessing the new CNV maps from the "Database of Genomic Variants" (http://www.projects.tcag.ca/variation/) hosted by SickKids. TCAG is a genomics platform funded by Genome Canada through OGI.

"Copy Number Variation has emerged over the past few years as a novel and productive focus for understanding variation within the human genome as well as other species' genomes," noted Dr. Christian Burks, President and CEO of the Ontario Genomics Institute (OGI). "We are delighted, in conjunction with funding from Genome Canada and Ontario's Ministry of Research and Innovation, to be supporting this work, and to see Ontario and Canada at the forefront of this area of biomedical research."

"From our Phase 1 map, we suspected there remains much more CNV to be discovered," said Dr. Matthew Hurles, Investigator at the Wellcome Trust Sanger Institute. "Because of the higher resolution of the new systems, we will, for the first time, be able to uncover these smaller variants."

Dr. Nigel Carter, Senior Investigator at the Sanger Institute added, "The availability of flexible high-density oligonucleotide arrays has made a study of such scope possible. The first data from the 42 million probe set has confirmed the ability of this approach to identify copy number variants at least as small as 500 base pairs in size."

The new arrays will be used to scan DNA samples from dozens of individuals of diverse geographic background, in experiments designed to capture all CNVs with a frequency of five percent or greater in the world. As such, the project will generate more than 1.68 billion data points.

"We also anticipate being able to obtain fine-scale information on the anatomy of individual CNVs" said Dr Charles Lee, Director of Cytogenetics (Harvard Cancer Center), Brigham and Women's Hospital and Harvard Medical School. "Ultimately, the data generated from our Phase 2 studies will be important for disease association studies, cancer biomarker studies, and accurate interpretation of many genetic diagnostic tests."

The Centre for Applied Genomics (TCAG) is located in the Research Institute of The Hospital for Sick Children (SickKids), Toronto, and is a Science and Technology Platform of Genome Canada, funded by Genome Canada through the Ontario Genomics Institute. TCAG provides genomics infrastructure to facilitate a wide variety of research, including human genomics and disease, model organisms, and agricultural and food sciences. The Centre's services are available to all clients in the academic, government or private sectors. TCAG supports a number of large-scale Genome Canada projects, other national and international genomics efforts, as well as hundreds of additional researchers in Ontario, Canada, and worldwide.

http://www.tcag.ca

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2005, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK.

http://www.sanger.ac.uk/humgen/cnv/

Brigham and Women's Hospital (BWH) is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 800 physician-investigators and renowned biomedical scientists and faculty supported by more than $400M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative.

http://www.brighamandwomens.org
http://www.chromosome.bwh.harvard.edu

The Ontario Genomics Institute (OGI) is a private, not-for-profit corporation focused on providing leadership for Ontario in helping build a globally-competitive life sciences sector by creating leverageable genomics resources with top-notch research. Through its relationship with Genome Canada, the Ontario Ministry of Research and Innovation (MRI), and other private and public sector partners, OGI helps Ontario-based scientists secure funding for research in genomics and proteomics as well as for commercialization activities. OGI also focuses on the potential ethical and social issues that can arise with and from such research.

http://www.OntarioGenomics.ca

How Much Would It Cost To Tell Men That There Is A Male Biological Clock? How Much Money Would Be Lost By Preventing Austim, etc.?

The $2,000,000 for Mark Rothmeyer doesn't surprise me at all. Neither do the other expenses and salaries. If anyone is interested in the causes of autism and the history of its creation as a mysterious disorder go to the autism prevention blogspot. Autism, until 1994 used to be a diagnosis given for a very specific set of symptoms and it was sometimes considered the severest example of early childhood schizophrenia. The paper by Kanner on classical autism can be linked to on the site.


Autism Speaks never does anything to help anyone with autism, or prevent even one case of autism. The causes of autism are known, the way to prevent more autism is known in a percentage of cases. How to take a tragic disorder and turn it into a lucretive business venture is demonstrated again by Autism Speaks and the Institutions it funds.

.....................................................................................


GINGER of ADVENTURES IN AUTISM

Thursday, June 07, 2007
I Take Back Every Nice Thing I Have Ever Said About Autism Speaks

"I read this today and it just made me sick. I don't even have the words to comment on it."~Ginger
....................................................................................
I am a professional that has reviewed many non profit organization's IRS Form 990s. Autism Speaks Form 990 raises serious red flags. Serious. This is all from the official filing for 2006.





1. Three members of the Board of Directors received $2.5 million for their own organizations.

2. The President Mark Rothmeyer, just received a 5 year contract for about $2,000,000 including bonuses with no prior background with autism.

3. The grants are primarily going to those representing institutions that are reviewing the grants. There is no indication that these conflicts are independently reviewed

4. The location of this small and new foundation is in very expensive downtown New York facilities rented for $200,000 by the institution that is run by the Chairman of Autism Speaks.

5. A expense of a Private Jet plane for $57,000 was noted. This is very unusual for a new non profit groups.

6. The head of the scientific review received the majority of the funds for 2005 for his institution for a data base - almost $3 million

Since the funding is now from the public - and the advertising and promotion tugs at the publics heart strings with images of families in need - the funds collected MUST be about those it raises the money for.

The following are all taken from the Form 990 filing

Web Site $830,000
Software for the computer $514,000
Lawyers $440,000
Computers $337,000
Public relations $285,000
Office annual rent $200,000
HR consultant $110,000
Editorial Consultant $76,000
Private Jet Plane for someone that entertained $57,000


Mark Rothmeyer* $360,000
Peter Bell [$240,000?]
Alison Singer $168,000
Mr Ringall $150,000
Andy Shik $110,000

Remember all the above also gets significant fring benefits that
probably add.

Mark Rothmayer also can get $50,000 more with a bonus a year benefits

Do PR Firms Sell the Glamour of Older Fathering of Babies and For How Long Have They Been Doing This?

Terrific! Don't miss it."
--Molly Ivins
Publisher's Weekly describes Toxic Sludge Is Good For You as "a chilling analysis of the PR business...a cautionary reminder that much of the consumer and political world is created by for-hire mouthpieces in expensive neckties."
Since its publication in late 1995, Toxic Sludge has already gone into its sixth printing amid rave reviews. It's been featured on ABC-TV's Good Morning America, National Public Radio's Marketplace, and in scores of other radio, TV and print stories.


You've read the book, now see the video!WHAT REVIEWERS ARE SAYING
"A chilling expose."
--Tom Vanderbilt, Village Voice Literary Supplement, 11/95

"Toxic Sludge should appear on the short list of anyone serious about the study of public relations in the United States."
--Paul Swift, Public Relations Quarterly, Fall 1996

"An instant classic!"
--Norman Solomon, author

"Written with humor and outrage at the public relations industry's worst excesses."
--Utne Reader, January/February 1996

"A startling portrait of the poisoning of the American democratic process by the nation's professional spin doctors... exposes the bare-knuckled, invisible hand guiding and shaping public opinions."
--Will Fantle, The Progressive, 12/95

"A real eye-opener."
--O'Dwyer's PR Services Report, 10/95

"A font of knowledge on the anti-knowledge biz."
--Leslie Savan, Village Voice, 12/12/95

"A powerful indictment of an industry 'designed to alter perception, reshape reality and manufacture consent.' "
--Laura Castaneda, Dallas Morning News, 12/17/95

"Terrific! Don't miss it."
--Molly Ivins, author

"Revealing and motivating."
--Ralph Nader, consumer advocate

"Important ... unmasks how corporations manipulate our democracy."
--William Greider, author, Who Will Tell The People

"Exposes how far we've tumbled down the dark hole of 'Newspeak' that Orwell warned about ... it could be the flashlight to find our way out."
--Jim Hightower, author and commentator

"A well-written, enlightening look at a war of the powerful against society."
--Edward Herman, co-author, Manufacturing Consent

"Great book - I love it!"
--Bill Lutz, founder, Doublespeak Quarterly

"Helps us see corporate crime and media distortion up close."
--Jeff Cohen, Executive Director, Fairness & Accuracy In Reporting (FAIR)

"Powerful."
--Ben Bagdikian, author, The Media Monopoly

TABLE OF CONTENTS
Acknowledgments

Introduction: Torches of Liberty, by Mark Dowie

CHAPTERS

Burning Books Before They're Printed
The Art of the Hustle and the Science of Propaganda
Smokers' Hacks
Spinning the Atom
Spies For Hire
Divide and Conquer
Poisoning the Grassroots
The Sludge Hits the Fan
Silencing Spring
The Torturers' Lobby
All the News That's Fit to Print
Taking Back Your Own Back Yard
APPENDICES

PR Industry Leaders

The Clorox PR Crisis Plan

Suggested Reading

Notes


hat tip

Men who wait until they are older to have children are not only risking difficulities conceiving they are increasing the risk of genetic problems

Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.



June 5, 2006
NR-06-06-01

Study shows that genetic quality
of sperm deteriorates as men age

New research indicates that the genetic quality of sperm worsens as men get older, increasing a man’s risk of being infertile, fathering unsuccessful pregnancies and passing along dwarfism and possibly other genetic diseases to his children.

A study led by scientists at Lawrence Livermore National Laboratory (LLNL) and the University of California, Berkeley, found a steady increase in sperm DNA fragmentation with increasing age of the study participants, along with increases in a gene mutation that causes achondroplasia, or dwarfism. The first changes were observed in men in their early reproductive years.


LANL
Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.
Earlier research by the same team indicated that male reproductive ability gradually worsens with age, as sperm counts decline and the sperm lose motility and their ability to swim in a straight line. In the current study, the researchers analyzed DNA damage, chromosomal abnormalities and gene mutations in semen samples from the same subjects – 97 healthy, non-smoking LLNL employees and retirees between 22 and 80 years old – and found that sperm motility showed a high correlation with DNA fragmentation, which is associated with increased risk of infertility and a reduced probability of fathering a successful pregnancy.

The study, “Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies (chromosome abnormalities) in sperm,” appears this week in the online edition of the Proceedings of the National Academy of Sciences.

“This study shows that men who wait until they’re older to have children are not only risking difficulties conceiving, they could also be increasing the risk of having children with genetic problems,” said co-lead author Andrew Wyrobek of LLNL.

“We know that women have a biological time clock,” said co-lead author Brenda Eskenazi of UC Berkeley’s School of Public Health, “with an increase in risk of miscarriage and producing children with trisomy (an extra chromosome, such as in Down’s syndrome) as women age, and with a seemingly abrupt end of fertility around perimenopause. Our research suggests that men, too, have a biological time clock – only it is different. Men seem to have a gradual rather than an abrupt change in fertility and in the potential ability to produce viable healthy offspring.”



May 2007 PATERNAL AGE AND AUTISM ARE ASSOCIATED IN A FAMILY-BASED SAMPLE

: Mol Psychiatry. 2007 May;12(5):419-421.Paternal age and autism are associated in a family-based sample.Cantor RM, Yoon JL, Furr J, Lajonchere CM.
[1] 1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [2] 2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [3] 3AGRE Consortium, Los Angeles, CA, USA.

PMID: 17453057 [PubMed - as supplied by publisher]


The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.
Labels: CM Lajonchere, J Furr, JL Yoon, RM Cantor

OLDER DADS PAST 33 THE RISKS RISE WITH INCREASING PATERNAL AGE

The link between schizophrenia and older paternity had been made before, but this was the first large study to look at a range of factors that could confound the results, said Professor John McGrath, a psychiatric epidemiologist at the Queensland Centre for Mental Health Research.

"If all babies had fathers less than 30, the paper suggests, the incidence of schizophrenia would reduce by 15 per cent," he said.

In 2002 the average age of fathers was 32, compared with an average age of 29 in 1982, according to data from the Australian Bureau of Statistics.

The executive director of the mental health lobby group SANE Australia, Barbara Hocking, said the Swedish research, published in the British medical journal BMJ, was "major, major stuff".

She likened the research to the link between mothers over 35 and an increased risk of Down syndrome in their children. "It helps people understand what risk factors may be, so you can take action to reduce them."




Obstetrics & Gynecology 1981;57:745-749
© 1981 by The American College of Obstetricians and Gynecologists


Genetic disease in the offspring of older fathers
JM Friedman


Autosomal dominant genetic diseases may result from the transmission of a trait by a carrier parent or from gene mutation in one of the gametes from which the child develops. The mean age of fathers of affected persons has been found to be greater than expected for several autosomal dominant diseases due to new mutations. To assess the clinical importance of this observation, the relative and absolute frequencies of offspring with autosomal dominant diseases due to mutation in the sperm from fathers of various ages have been calculated. The relative frequency of new autosomal dominant mutations in children increases logarithmically with paternal age during the usual years of fatherhood. The absolute frequency of autosomal dominant disease due to new mutations among the offspring of fathers who are 40 years of age or older is estimated to be at least 0.3 to 0.5%. This risk is many times greater than that for children of young fathers and is similar in magnitude to the risk of Down syndrome among the offspring of 35- to 40-year-old mothers. Thus, it is good public health policy to recommend that both men and women complete their family a before age 40, if possible.




Combined Effect of Older Mothers and Fathers Increases Baby's Risk
By Jennifer Warner
WebMD Medical NewsReviewed by Brunilda Nazario, MDJuly 1, 2003 -- Older fathers may contribute just as much as older mothers to the dramatic increase in Down syndrome risk faced by babies born to older couples. A new study found that older fathers were responsible for up to 50% of the rise in Down syndrome risk when the mother was also over 40.

Researchers say the number of births to parents over age 35 has more than doubled in the last 20 years and this has raised questions about the role of paternal age in the risk of genetic abnormalities and birth defects.

Previous studies have shown that the risk of a woman having a baby with Down syndrome rises dramatically after she reaches 35. Although this effect of maternal age on Down syndrome risk is well known, researchers say the influence of the father's age on Down syndrome has not yet been defined. Some studies have found no relationship, while other, smaller studies have suggested that older fathers may raise the risk of Down syndrome.

But researchers say this study, published in The Journal of Urology, is the largest of its kind and looked at 3,429 Down syndrome cases reported to the New York State Department of Health from 1983 to 1997. Their findings suggest that the increase in the number of babies with the genetic abnormality born to women over 35 may be the result of a combined effect of both advanced maternal and paternal ages.

Older Fathers Face More Risks
The study showed that the percentage of births to women over 35 grew from 8% of all births in 1983 to 17% in 1997, and the greatest change during this period was the number of births to mothers and fathers over 40 years old, which rose by 178% and 73%, respectively.

Researchers found that the rate of Down syndrome among parents over 40 was 60 per 10,000 births, which is six times higher than the rate found among couples under 35 years old. Older fathers over 40 had twice the rate of Down syndrome births compared with men 24 years old and younger when they had children with women over 35.

"Paternal age has an effect on Down syndrome but only in mothers 35 years old and older," write researcher Harry Fisch, MD, of the department of urology at Columbia-Presbyterian Medical Center in New York City, and colleagues. "In younger women, in whom age was not a risk factor for Down syndrome, there was no paternal effect."

Among older mothers over 40, researchers found that an increase of 50% in Down syndrome risk was attributable to the advanced age of the father.

In fact, researchers suggest that there is only a modest increase in Down syndrome risk for women 35-39 compared with women 30-35 years old, but the dramatic increase in Down syndrome births among women 35 to 39 years old is largely due to the influence of older fathers because older women tend to make babies with older men.

THE IDEA THAT GERM LINE CNVs OCCUR IN THE SPERM OF OLDER MEN IS CERTAINLY A POSSIBILITY AND A VERY IMPORTANT RESEARCH LINE TO FOLLOW IN SZ AND AUTISM

"The idea that germ line CNVs occur in the sperm of older men (or women for that matter) is certainly possible and a very important research line to follow in schizophrenia and autism. However, the best experiment would be to identify de novo CNVs in patients with SZ by doing CGH and comparing the results with parental CGH (as recently reported by Sebat et al in autism). The possibility of a finding might increase if sporadic, non-familial cases are used. One cannot examine the sperm directly because the frequency of such a defect would be very low and the spermatozoan with a new CNV would be diluted by a large population of cells that do not have it. The sensitivity of current methods used to assess CNV are too low to detect such changes."

A MAJOR INFLUENCE ON NEW MUTATIONS IN THE HUMAN GENE POOL IS RELATED TO THE ADVANCING AGE OF FATHERS

"As a major influence on new mutations in the human gene pool is related to the advancing age of fathers, Dr. Malaspina first examined the relationship of schizophrenia and paternal age. Data showed a strong escalation in schizophrenia risk as the age of the father increased, accounting for over a quarter of the schizophrenia cases. Another of her studies found that fathers of sporadic schizophrenia cases were 5 years older than familial case fathers. If sporadic schizophrenia can originate from new mutations, then neurodevelopmental genes are reasonable candidates. Her study will examine if patients with sporadic schizophrenia, particularly those with fathers older than 35 at birth, show features found in other neurodevelopmental diseases that correlate with paternal age, such as craniofacial abnormalities, nonspecific cognitive deficits and delayed developmental milestones. However, if genes that arise from mutations are inherited by later generations, then some familial cases with a similar illness would not have a paternal age effect. Dr. Malaspina plans to define the clinical profile in sporadic patients associated with paternal age through group comparisons and cluster analysis. If the study is successful, this illness pattern may be useful in gene identification for schizophrenia."


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