Sunday, March 02, 2014

Children born to older fathers have a higher incidence of autism and poor performance at school

Some of the effects reported in this study are astoundingly strong (e.g. for ADHD and bipolar) -- much stronger than what has been found in earlier studies of  similar populations (e.g. here).  That does of itself suggest some artifact.  The obvious artifactual confounder -- social class -- was however taken into account in the study design.  Paternal education and income were controlled for.  The remaining possibility is IQ.  It seems likely that low IQ Swedish men might have difficulty partnering and consequently tend to produce children much later in life.  And IQ is of course associated with all sorts of health variables.  I would have to be more familiar with Swedish culture and society to suggest other confounders, however

Children born to older dads run a higher risk of having autism, psychiatric disorders and performing badly at school, researchers have warned.

They found children conceived when fathers were 45 and older were on average three and a half times more likely to have autistic problems compared with the offspring of men in their early 20s.

The risk was even higher at 24-fold for bipolar disorder and 13-fold higher for ADHD, says a report in JAMA Psychiatry journal.

Researchers warned that advancing paternal age posed a risk of `numerous public health and societal problems'.

They said men should be advised about the potential problems in order to help their personal decision-making when it came to having fathering children at older ages.

Among well-known older dads are Simon Cowell, 54, whose son was born earlier this month, and comedian Frank Skinner whose first child was born in 2012 when he was 55.

Mounting research suggests the older age of parents might be partly responsible for growing numbers of children with autism.

Autism is an umbrella term for a range of developmental disorders that have a lifelong effect on someone's ability to interact socially and communicate.

In the UK, around one in 100 adults is thought to be affected by autism, mostly men, caused by a combination of genetic and environmental factors.

Experts think the link with paternal age could be explained by genetic errors creeping into sperm production as men get older, which build up over time.

In the latest study, researchers studied people born in Sweden from 1973 to 2001 and estimated the risk of psychiatric problems such as autism, bipolar disorder and attention deficit hyperactivity disorder, and academic trouble.

The study used several models to establish estimates of risk depending on the father's age, including comparisons of siblings, cousins and first-born cousins.

It concluded there was a 3.5 fold higher risk of autism among children of fathers aged 45 and over, compared with dads aged 20 to 24 years old.

Those born to older fathers had a 13-fold extra risk of ADHD, 24-fold higher risk of bipolar disorder, and double the risk of suicide attempts and substance abuse.

There was also a higher risk of academic problems such as failing a grade and low attainment.

Researcher Brian D'Onofrio, of Indiana University, Indiana, U.S., said: `Advancing paternal age is associated with an increased risk of psychiatric and academic morbidity, with the magnitude to risks being as large, or larger, than previous estimates.'

Dr D'Onofrio added: `We were shocked by the findings.

`The specific associations with paternal age were much, much larger than in previous studies. In fact, we found that advancing paternal age was associated with greater risk for several problems, such as ADHD, suicide attempts and substance use problems, whereas traditional research designs suggested advancing paternal age may have diminished the rate at which these problems occur.'

Previous studies have shown that fathers aged 50 and older are more than twice as likely to have a child diagnosed with autism than younger fathers, while some research suggests older mothers may also be more at risk.


Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity

Brian M. D'Onofrio et al.


Importance:  Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors.

Objective:  To examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity.

Design, Setting, and Participants:  We performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N?=?2?615?081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins.

Exposure:  Paternal age at childbearing.

Main Outcomes and Measures:  Psychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity.

Results: In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings.

Conclusions and Relevance:  Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.

JAMA Psychiatry. Published online February 26, 2014

The pill that could slow aging: Researchers reveal groundbreaking study to extend lifespan and improve health of  elderly mice

A groundbreaking new study could hold the key to living longer and remaining healthy in old age.

US researchers found a protein called SIRT1 extended the lifespan of mice, delaying the onset of age related health problems.

It also improved their general health, lowering cholesterol and even warding off diabetes.

Although the study was carried out in mice, researchers say it could eventually be used in humans.

Researchers led by Dr. Rafael de Cabo of the National Institute on Aging at the National Institutes of Health tested the effects of a small molecule that activates SIRT1, called SIRT1720, on the health and lifespan of mice.

'Here, we show for the first time that a synthetic SIRT1 activator extends lifespan and improves healthspan of mice fed a standard diet,' says Dr. de Cabo.

'It illustrates that we can develop molecules that ameliorate the burden of metabolic and chronic diseases associated with aging.'

The researchers also found that SRT1720 significantly extended the average lifespan of mice by 8.8 percent.

Supplementation also reduced body weight and body fat percentage, and it improved muscle function and motor coordination throughout the animals' lives.

The investigators found that SRT1720 supplementation led to decreases in total cholesterol and LDL-cholesterol levels, which might help protect against heart disease, and improvements in insulin sensitivity, which could help prevent diabetes.

SIRT1 and its sister protein SIRT2 are known to play a important roles in metabolism across a wide range of species.

They are involved in DNA repair and gene regulation, and may help to prevent diabetes, heart disease and cancer.

The animals were given the supplement from the age of six months and for the rest of their lives, alongside a standard diet.

However, experts warn the study is still at a very early stage, and had not yet been tested in humans.


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