The number of men ages 35-49 who father children has increased 40 percent since 1980 while the number of fathers under 30 has fallen 20 per cent

Research finds sperm quality drops, genetic problems rise as men age
Sabin Russell, Chronicle Medical Writer

Tuesday, June 6, 2006


With a lineup of Bay Area men at their disposal, Lawrence Livermore scientists have deflated yet another cherished male fantasy -- that sperm quality resists the ravages of age.

In fact, the genetic quality of sperm deteriorates as time goes by.

The Livermore analysis of sperm samples from men ages 22-80 found a gradual but steady increase in the percentage of genetic mutations over time, raising the risk of infertility and of fathering children with genetic abnormalities.

Until now, men had some reason to think their sperm could stand the test of time: Sperm are generated continuously in the testes from sexual maturity through old age. A woman's supply of eggs, on the other hand, is produced before birth. Because the eggs age with her, the risk for some chromosomal anomalies such as Down syndrome linked to egg defects increase with a pregnant woman's age.

The study found that although an older man's sperm does not increase the likelihood of Down syndrome, other genetic conditions such a dwarfism can be passed on with greater frequency by older men.

"There is a reproductive consequence to delaying fatherhood,'' said Andrew Wyrobek, a senior staff biophysicist at the Livermore National Laboratory, and lead author of the study published today in the Proceedings of the National Academy of Sciences.

It is an issue of increasing relevance as men as well as women defer parenthood to a later age in the United States. The number of men ages 35-49 who father children has increased 40 percent since 1980, according to Wyrobek, while the number of fathers under 30 has fallen 20 percent. .................................



Co-lead author Barbara Eskenazi said: "We know that women have a biological time clock. 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 to produce viable healthy offspring."


But it found a steady increase in the amount of broken DNA strands as the age of the subjects increased. This genetic damage can translate into fertility problems, pregnancy failures and an increase in some genetic diseases.

As the men aged, the researchers found that the number of genetic mutations that can cause dwarfism increased in the sperm with the age of the men -- at a rate of about 2 percent per year.

Wyrobek stressed that, although the trend toward genetic deterioration with age was clear, there were disparities in sperm quality among the men within each age group. Even in the oldest cohort, there were some men with few genetic mutations in their sperm, while others had multiple abnormalities.

Study Says Male Fertility Falls After 35

Human fertility starts to decline earlier than previously believed, new research suggests, providing the most precise insight yet into when biological clocks start ticking loudly ? at age 27 for women and 35 for men.

Until now, it was thought that women's fertility starts to drop significantly in the early 30s, with a big plunge after 35. But the new study indicates that, on average, female fertility begins its meaningful slide at age 27.

And while the decline in human fertility tied to aging had traditionally been attributed to the female factor, the study, published Tuesday in the journal Human Reproduction, showed that men's fertility starts dwindling after 35.

and

A recent report from the Journal of the American Medical Association looks at past research to examine why aging men experience declining fertility.

It appears that men older than 35 are twice as likely to be infertile as men younger than 25.


As men age, both the number and quality of their sperm decline — so older men become less likely to father a child and more likely to father a child with schizophrenia, Down syndrome, or other problems.

A recent study suggests that autism, an increasing problem with no known cause, may also be linked to paternal age because men 40 years or older are almost six times more likely to have a child with an autism disorder than men younger than 30.

Miscarriages also are more common as dad gets older.


It's not unusual for a woman to get her hormones, ovulatory function and fallopian tubes tested months before her husband has even had a basic semen analysis.

Given that 20 percent of couples are infertile because of abnormal or absent sperm and that 27 percent of infertile couples have a combination of male and female factors, it makes sense to evaluate a man's equipment, so to speak, sooner rather than later.

Alzheimer's and Paternal Age & Myelin

George Bartzokis,M.D.


Visiting Professor

Laboratory of Neuro Imaging,
Department of Neurology, UCLA School of Medicine
635 Charles Young Drive South, Suite 225
Los Angeles, CA 90095-7332



Education

1975-1979, BA Harvard University, Cambridge, MA
1979-1983, MD Yale Medical School, New Haven, CT
1983-1984, Internship, UCLA/WLA VA, Los Angeles, CA
1984-1987, Psychiatry Residency, UCLA NPI, Los Angeles, CA
1987-1990, Schizophrenia Research Fellow, UCLA Dept of Psychology, Los Angeles, CA


Research

Development of brain imaging biomarkers for use in diagnosis of neuropsychiatric disorders and medication development
Assessing brain maturation and degeneration trajectories over the life-span in normal populations and how neuropsychiatric disorders interact with these processes


Projects

Myelin breakdown in aging and Alzheimer's disease
In vivo quantification of age-related increases in brain iron levels
Evaluation of brain maturational trajectories in normal adults and patientss with neuropsychiatrc diseases


Skills

Quantification of brain iron levels
Quantification of limbic structures volumes
Quantification of brain myelination
Quantification of myelin integrity
Clinical trials
Administration of multidisciplinary teams


Honors

U.S. Patent, Method for Quantitatively Measuring Stored Iron in Tissue Using MRI










This quote is not from a published paper.
I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth.



"The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations.
The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."

THE AGE OF THE FATHER AND THE HEALTH OF FUTURE GENERATIONS

THE AGE OF THE FATHER AND THE
HEALTH OF FUTURE GENERATIONS
Word Count: 903
　
Leslie B. Raschka M.D., Associate Professor (retired),
Department of Psychiatry, University of Toronto
Address: 27 Edgecombe ave, Toronto, Ontario, Canada
M5N 2Xl, Tel. (416) 783-6938
2
Abstract
Purpose: To assess the role of paternal age in the origin of genetic illness in future generations.
Data Sources: All reference data originated in English language international scientific literature and findings of original research conducted by myself.
Study Selection: Original articles published between 1938 and 1998 were selected according to the stated purpose. One article was written by myself.
Data Extraction: The present paper deals with 4 subtopics: andrology, genetics, pathology, and psychiatry.
Results: Nine articles reporting on 1399 patients described the deterioration of the quality of semen related to ageing. Five articles reported an increased mutation rate in the male germ cells as compared to the female germ cell. Twenty-four articles reported on 1230 patients and related studies described paternal age effect on increased mutation rate causing genetic illness. Eight articles reporting on 10,347 patients described increased prevalence of mental illness as related to older paternal age.
Conclusions: 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.
3The genetic illness of a child could originate in a mutation related to the age of the father or to a mutation in the spermatogenesis caused by ageing in previous generations. The ageing process in the male is an important, probably the most important, cause of genetic illness in human populations.
　Key Words: Age of the father, mutation, genetic illness
4 Demographic changes taking place in the 20th Century have directed attention to all possible determinants of the health of future generations. The relationship between maternal age and Down Syndrome is a currently recognized scientific fact. The study of the reproductive efficiency of the male is also relevant to the health of future generations. Most children are born healthy regardless of paternal age; however, the age of the father is a determinant of ill health for a significant minority in future generations.
　
5 Andrology
Ageing in the male is expressed in a progressive decline both in the quality and quantity of the sperm (1). Changes include a decrease in motility (2), decreased vitality and an increased percentage of malformed sperm (3, 4, 5, 6, 7). The deterioration associated with ageing can be noticed first in men between the ages of 35 to 40 years (8, 9).
　
6 Genetics
The mutation rate is higher in the male than in the female germ cell (10, 11, 12, 13, 14). While the ageing male germ cell is especially sensitive to mutation (15) there is a significant difference in mutation, rates among different genes. There is evidence that mutation frequencies for a number of different genes causing illness increase with advancing paternal age. The rate of increase differs among different genes (16); not all genes are subject to the paternal age effect. Almost all new mutations were reported to occur in the male germ cell; however, paternal age effect is not equally pronounced in all mutations (12). It is operant in recent germline mutations. Inherited illnesses such as hemophilia A have their origins in mutations in earlier generations where, for example, increased maternal grandparental age was found and new germline mutation related to increased paternal age transmitted to future generations can result in hereditary illness. In the development of illness, more than one gene can be involved. The phenotypic expression can be influenced by modifying genes. The importance of mutations for the health of future generations was born out by the Bulletin of the World Health Organization 1986 (17), which states that about 1% of children will be born with a serious genetic disease and another 1% will develop a serious genetic illness later in life.
7 Pathology
The relationship between increased paternal age and pathological conditions of known genetic origin was reported for achondroplasia in nineteen publications (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34); for Apert Syndrome in sixteen publications (15, 19, 20, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35); on Marfan Syndrome in thirteen publications (15, 20, 21, 22, 23, 25, 26, 27, 30, 31, 32, 33, 34); on osteogenesis imperfecta in five publications (16, 19, 24, 25, 29); on basal cell naevus syndrome in three publications (22, 26, 32); in Waardenburg Syndrome in five publications (22, 26, 31, 32, 33); on Crouzon Syndrome in seven publications (22, 26, 28, 31, 32, 33, 35); on oculo-denta; digital syndrome in four publications (22, 26, 31, 32); on thanatophoric dysplasia in three publications (28, 29, 35); on Pfeiffer Syndrome in three publications (28, 32, 35); on tuberous sclerosis in three publications (31, 33, 36); on multiple endocrine neoplasm in three publications (32, 34, 37); on myositis ossificans in nine publications (15, 19, 21, 22, 24, 30, 31, 32, 33); and on Treacher Collins disease, four publications (22, 26, 31, 33). All of these illnesses are transmitted in an autosomal dominant fashion. Increased risk for X-linked conditions associated with increased maternal grand-parental age is known to exist regarding classical hemophilia and was reported in nine publications (15, 17, 23, 25, 26 31, 32, 34, 38). This is also true for Lesch-Nyhan syndrome, reported in five publications (10, 17, 27, 31, 38). The mutation is transmitted to the child through carrier mothers.
8Psychiatry
Mutations occurring in the course of gametogenesis in the male and the association of psychosis was described in one article (39). Older maternal and paternal age in schizophrenia was reported in four articles (39, 40, 41, 42). My own study involving 574 patients has shown that the increased age of the father is a causative factor in a sub-group of the schizophrenic population (43). Two other articles, reporting on 662 and 8000 patients respectively, confirmed my conclusions, as well as indicating that increased maternal age was secondary to increased paternal age (41, 42). Three articles reporting on 1081 patients described increased paternal age in Alzheimer’s disease (44, 45, 46).
　
9 Discussion
All genetic illnesses have their origin in a distant or recent mutation. Paternal age is an important determinant of mutation frequency in new germ cell mutation, causing both autosomal dominant and X-linked recessive illnesses. The role of other mutagenic factors is not the subject of this study. The results of my own research are supported by other information which indicates that the leading cause of genetic illness present in human populations is the ageing process in the male. Conceiving children by men younger than 35 years of age would prevent many genetic illnesses in future generations.
　
10 Bibliography
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3. Urikami K, Adachi Y, Takahashi K. A Community-Based Study of Parental Age in Alzheimer-Type Dementia in Western Japan. Arch Neurol 1988; 45: 375.
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Diabetes age of parents etc risk factor 2005

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