Older fathers' children have lower evolutionary fitness across four centuries and in four populations

Higher paternal age at offspring conception increases de novo genetic mutations. Based on evolutionary genetic theory we predicted older fathers' children, all else equal, would be less likely to survive and reproduce, i.e. have lower fitness. In sibling control studies, we find support for negative paternal age effects on offspring survival and reproductive success across four large populations with an aggregate N > 1.4 million. Three populations were pre-industrial (1670–1850) Western populations and showed negative paternal age effects on infant survival and offspring reproductive success. In twentieth-century Sweden, we found minuscule paternal age effects on survival, but found negative effects on reproductive success. Effects survived tests for key competing explanations, including maternal age and parental loss, but effects varied widely over different plausible model specifications and some competing explanations such as diminishing paternal investment and epigenetic mutations could not be tested. We can use our findings to aid in predicting the effect increasingly older parents in today's society will have on their children's survival and reproductive success. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time periods.

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Older fathers' children have lower evolutionary fitness across four centuries and in four populations

10.1101/042788 ◽

2016 ◽

Cited By ~ 1

Author(s):

Ruben C. Arslan ◽

Kai P. Willführ ◽

Emma Frans ◽

Karin J. H. Verweij ◽

Mikko Myrskylä ◽

...

Keyword(s):

De Novo ◽

Child Survival ◽

Genetic Load ◽

Age Effects ◽

Paternal Age ◽

De Novo Mutations ◽

Delayed Reproduction ◽

Large Populations ◽

Sibling Control ◽

Control Study

Higher paternal age at offspring conception increases de novo genetic mutations (Kong et al., 2012). Based on evolutionary genetic theory we predicted that the offspring of older fathers would be less likely to survive and reproduce, i.e. have lower fitness. In a sibling control study, we find clear support for negative paternal age effects on offspring survival, mating and reproductive success across four large populations with an aggregate N > 1.3 million in main analyses. Compared to a sibling born when the father was 10 years younger, individuals had 4-13% fewer surviving children in the four populations. Three populations were pre-industrial (1670-1850) Western populations and showed a pattern of paternal age effects across the offspring's lifespan. In 20th-century Sweden, we found no negative paternal age effects on child survival or marriage odds. Effects survived tests for competing explanations, including maternal age and parental loss. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time. We can use this understanding to predict the effect of increasingly delayed reproduction on offspring genetic load, mortality and fertility.

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Impact of Paternal Age at Conception on Human Health

Clinical Chemistry ◽

10.1373/clinchem.2018.294421 ◽

2019 ◽

Vol 65 (1) ◽

pp. 146-152 ◽

Cited By ~ 8

Author(s):

Mathieu Simard ◽

Catherine Laprise ◽

Simon L Girard

Keyword(s):

Maternal Age ◽

De Novo ◽

Autism Spectrum ◽

Age Effect ◽

Age Effects ◽

Paternal Age ◽

De Novo Mutations ◽

Brain Functions ◽

Offspring Health ◽

Paternal Age Effect

Abstract BACKGROUND The effect of maternal age at conception on various aspects of offspring health is well documented and often discussed. We seldom hear about the paternal age effect on offspring health, although the link is now almost as solid as with maternal age. The causes behind this, however, are drastically different between males and females. CONTENT In this review article, we will first examine documented physiological changes linked to paternal age effect. We will start with all morphological aspects of the testis that have been shown to be altered with aging. We will then move on to all the parameters of spermatogenesis that are linked with paternal age at conception. The biggest part of this review will focus on genetic changes associated with paternal age effects. Several studies that have established a strong link between paternal age at conception and the rate of de novo mutations will be reviewed. We will next discuss paternal age effects associated with telomere length and try to better understand the seemingly contradictory results. Finally, severe diseases that affect brain functions and normal development have been associated with older paternal age at conception. In this context, we will discuss the cases of autism spectrum disorder and schizophrenia, as well as several childhood cancers. SUMMARY In many Western civilizations, the age at which parents have their first child has increased substantially in recent decades. It is important to summarize major health issues associated with an increased paternal age at conception to better model public health systems.

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Parental breeding age effects on descendants’ longevity interact over two generations in matrilines and patrilines

10.32942/osf.io/mnx8h ◽

2019 ◽

Author(s):

Zac Wylde ◽

Foteini Spagopoulou ◽

Amy K Hooper ◽

Alexei A Maklakov ◽

Russell Bonduriansky

Keyword(s):

Maternal Age ◽

First Generation ◽

Age Effects ◽

Population Variation ◽

Paternal Age ◽

Interactive Effects ◽

Competitive Environment ◽

Larval Diet ◽

Negative Effects ◽

Two Generations

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does, and that breeding age effects can interact over two generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over two generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grandparental ages at breeding on descendants’ mortality rate and lifespan in both matrilines and patrilines. These breeding age effects were not modulated by grandparental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intra-population variation in mortality and longevity.

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Schizophrenia Risk and Paternal Age: A Potential Role for De Novo Mutations in Schizophrenia Vulnerability Genes

CNS Spectrums ◽

10.1017/s1092852900022239 ◽

2002 ◽

Vol 7 (1) ◽

pp. 26-29 ◽

Cited By ~ 27

Author(s):

Dolores Malaspina ◽

Alan Brown ◽

Deborah Goetz ◽

Nelly Alia-Klein ◽

Jill Harkavy-Friedman ◽

...

Keyword(s):

Human Population ◽

Potential Role ◽

De Novo ◽

Paternal Age ◽

Current Evidence ◽

Parental Age ◽

De Novo Mutations ◽

New Mutations

ABSTRACTHow schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis.

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Parental Age and Schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.112.490.899 ◽

1966 ◽

Vol 112 (490) ◽

pp. 899-905 ◽

Cited By ~ 22

Author(s):

K. L. Granville-Grossman

Keyword(s):

Maternal Age ◽

Age Effect ◽

Age Effects ◽

Paternal Age ◽

Considerable Importance ◽

Parental Age ◽

Advanced Paternal Age ◽

Older Parents ◽

Maternal Age Effect ◽

Environmental Causes

Reports that schizophrenics have older parents than non-schizophrenics (Barry, 1945; Goodman, 1957; Johanson, 1958; Gregory, 1959) are of considerable importance. If valid, they provide evidence for environmental causes of schizophrenia, and by analogy with other conditions where parental age effects have been noted may give some indication of the nature of these causes. There are, however, inconsistencies in these studies: thus Johanson and Gregory found a significant association between advanced paternal age and schizophrenia, but failed to confirm the maternal age effect noted by Barry and Goodman. These differences indicate the need for further investigation and this paper describes such a study.

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Advancing paternal age and offspring violent offending: A sibling-comparison study

Development and Psychopathology ◽

10.1017/s095457941200034x ◽

2012 ◽

Vol 24 (3) ◽

pp. 739-753 ◽

Cited By ~ 12

Author(s):

Ralf Kuja-Halkola ◽

Yudi Pawitan ◽

Brian M. D'Onofrio ◽

Niklas Långström ◽

Paul Lichtenstein

Keyword(s):

Violent Crime ◽

De Novo ◽

Causal Effect ◽

Paternal Age ◽

De Novo Mutations ◽

Criminal Convictions ◽

Violent Offending ◽

Genes And Environment ◽

Life Course Persistent ◽

Severe Psychopathology

AbstractChildren born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly because of increased de novo mutations during spermatogenesis with older paternal age. Because severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers' age at childbirth and violent criminal convictions in all offspring born from 1958 to 1979 (N= 2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-family analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending.

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