Effect Of Parental Age Research Articles

Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort.

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring's TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants' TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan.

Reproductive aging weakens offspring survival and constrains the telomerase response to herpesvirus in Pacific oysters.

Telomere length (TL) is increasingly recognized as a molecular marker that reflects how reproductive aging affects intergenerational transmissions. Here, we investigated the effects of parental age on offspring survival and the regulation of TL by examining the telomere-elongating activity of telomerase in the Pacific oyster. We assessed the classical hallmarks of aging in parents at three age classes (young, middle-aged, and old) and crossbred them using a split-brood design to examine the consequences of the nine maternal-by-paternal age combinations on their offspring. Reproductive aging leads to increased larval mortality and accelerated telomere shortening in spats, rendering them more susceptible to infection by the Ostreid herpesvirus. Viral exposure stimulates telomerase activity, a response that we identified as adaptive, but weakened by parental aging. While telomerase lengthens a spat's telomere, paradoxically, longer individual TL predicts higher mortality in adults. The telomerase-telomere complex appeared as a conservative biomarker for distinguishing survivors and losers upon exposure to polymicrobial diseases.

The effect of parental age on the quantity and quality of offspring in Syngnathus typhle, a species with male pregnancy.

Parental age impacts offspring quantity and quality. Most prior research focused on maternal age. Since in most organisms the mother produces the costly eggs plus provides all or most parental care, it is difficult to distinguish maternal effects mediated via the egg from later maternal care. Here, we addressed the effects of parental age on offspring in Syngnathus typhle, a pipefish with male pregnancy. The divide between one parent producing the eggs and the second parent being the exclusive provider of parental care facilitates a distinction between the effects of parental age on egg quality versus parental age on early development. We fully reciprocally crossed young and old mothers and young and old fathers and assessed impact of parental age combination on offspring number, offspring size, and offspring gene expression patterns. Neither parental combination significantly influenced offspring size or male gestation duration; however, they influenced the number of offspring. Paternal, but not maternal, age strongly affected the offspring gene expression. Offspring from old fathers exhibited substantial changes in the expression of genes related to cell cycle regulation, protein synthesis, DNA repair, and neurogenesis. Our findings thus highlight the importance of gestation, as opposed to gamete production, in shaping the parental contribution to offspring development.

Effect of parental age on developmental rate polymorphism of the ladybird beetle, Propylea dissecta

Effect of parental age on developmental rate polymorphism of the ladybird beetle, Propylea dissecta

The effect of parental age on child development at 36 months: Insights from the Japan environment and children's study

BackgroundThe impact of parent-childbearing age on child development at 36 months of age is controversial. AimsWe used data from a large cohort study with multiple imputation and mediation analyses of variables. Methods and ProceduresA total of 72,606 parent–child pairs from the Japan Environment and Children's Study were included in the study. Parents' ages were categorized into five groups. We used five domains of the Japanese translation of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3). Scores below the cutoff value at 36 months were defined as developmental delays in each domain. We used three logistic analysis models. In Model 3, we analyzed maternal and paternal age using other variables and covariates. Outcomes and ResultsThe outcome was a developmental delay in the five domains of J-ASQ-3. In Model 3, ORs for the developmental delay scores regarding parental age were significantly associated with all five domains of J-ASQ-3. The mediation analysis showed a significant mediation interaction effect for mothers but localized for fathers. ConclusionAdvanced paternal and maternal ages were associated with developmental delay in children. Awareness of the risks of childbearing at an advanced age is crucial. What’s the paper addsThis manuscript used data from a large cohort study with multiple imputation and mediation analyses. With these analyses, we identified the pure effect of advanced parental age on their children’s development at 36 months.

Effects of parental age and polymer composition on short tandem repeat de novo mutation rates.

Short tandem repeats (STRs) are hotspots of genomic variability in the human germline because of their high mutation rates, which have long been attributed largely to polymerase slippage during DNA replication. This model suggests that STR mutation rates should scale linearly with a father's age, as progenitor cells continually divide after puberty. In contrast, it suggests that STR mutation rates should not scale with a mother's age at her child's conception, since oocytes spend a mother's reproductive years arrested in meiosis II and undergo a fixed number of cell divisions that are independent of the age at ovulation. Yet, mirroring recent findings, we find that STR mutation rates covary with paternal and maternal age, implying that some STR mutations are caused by DNA damage in quiescent cells rather than polymerase slippage in replicating progenitor cells. These results echo the recent finding that DNA damage in oocytes is a significant source of de novo single nucleotide variants and corroborate evidence of STR expansion in postmitotic cells. However, we find that the maternal age effect is not confined to known hotspots of oocyte mutagenesis, nor are postzygotic mutations likely to contribute significantly. STR nucleotide composition demonstrates divergent effects on de novo mutation (DNM) rates between sexes. Unlike the paternal lineage, maternally derived DNMs at A/T STRs display a significantly greater association with maternal age than DNMs at G/C-containing STRs. These observations may suggest the mechanism and developmental timing of certain STR mutations and contradict prior attribution of replication slippage as the primary mechanism of STR mutagenesis.

#166 : Investigating the Effect of Parental Age on Intracytoplasmic Sperm Injection Reproductive Outcomes in Indonesia: Prognostic Tools and Prediction Approaches to Maximize Human Embryo Implantation

Background and Aims: Reproductive issues impact one in eight Indonesian married couples. Intra Cytoplasmic Sperm Injection (ICSI) is still expensive; hence many couples don’t get evaluated or enroll fertility programs. We decided to study the correlation between age, hormonal status, and ICSI embryo quality because Indonesia’s infertility rate is rising. This is the first investigation into the factors behind ICSI outcomes in Indonesia. Method: In 2022, two fertility centers in Surabaya and Tangerang, Indonesia, performed ICSI on couples. 150 couples receiving ICSI at two research sites comprise the sample. Surgically retrieved or frozen sperm cycles and incomplete medical records were excluded. The Spearman test was used to investigate the correlation between parental age, hormonal status, and ICSI embryo quality on day 1 and day 3. (D1 and D3). Results: 150 ICSI cycles were studied. The hormonal baseline varied from normal to subnormal, while paternal and maternal age ± SDs were 37.03 ± 6.08 and 34.28 ± 5.11. The Spearman test demonstrated a significant negative connection between paternal age and embryo quality D1 (p<0.005, r=-0.363) and D3 (good category: p<0.005, r=-0.172; intermediate category: p<0.005, r=-0.250; poor category: p<0.005, r=-0.221). The Spearman test showed a significant negative connection between maternal age and embryo quality D1 (p<0.005, r=-0.413) and D3 (good category: p<0.005, r=-0.231; intermediate category: p<0.005, r=-0.294; poor category: p<0.005, r=-0.291). Conclusion: This study reveals that married couples have a substantial impact on their hormonal condition, the rate of fertilization, the quality of D1 and D3 embryos, and the number of embryos generated following ICSI. To increase the success rate of ICSI procedures, it is necessary to maximize fertility at a younger age.

Parental age effect on the longevity and healthspan in Drosophila melanogaster and Caenorhabditis elegans.

Several studies have investigated the effect of parental age on biological parameters such as reproduction, lifespan, and health; however, the results have been inconclusive, largely due to inter-species variation and/or modest effect sizes. Here, we examined the effect of parental age on the lifespan, reproductive capacity, and locomotor activity of genetic isogenic lines of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. We found that the progeny of successive generations of old parents had significantly shorter lifespans than the progeny of young parents in both species. Moreover, we investigated the fertility, fecundity, and locomotor activity of C. elegans. Interestingly, both the shorter lifespan and deteriorated healthspan of the progeny were significantly improved by switching to only one generation of younger parents. Collectively, these data demonstrate that the detrimental effect of older parental age on the longevity of the progeny can be reversed, suggesting the existence of a beneficial non-genetic mechanism.

Germline mutation rate is elevated in young and old parents in Caenorhabditis remanei.

The effect of parental age on germline mutation rate across generations is not fully understood. While some studies report a positive linear relationship of mutation rate with increasing age, others suggest that mutation rate varies with age but not in a linear fashion. We investigated the effect of parental age on germline mutations by generating replicated mutation accumulation lines in Caenorhabditis remanei at three parental ages ("Young T1" [Day 1], "Peak T2" [Day 2], and "Old T5" [Day 5] parents). We conducted whole-genome resequencing and variant calling to compare differences in mutation rates after three generations of mutation accumulation. We found that Peak T2 lines had an overall reduced mutation rate compared to Young T1 and Old T5 lines, but this pattern of the effect varied depending on the variant impact. Specifically, we found no high-impact variants in Peak T2 lines, and modifiers and up- and downstream gene variants were less frequent in these lines. These results suggest that animals at the peak of reproduction have better DNA maintenance and repair compared to young and old animals. We propose that C. remanei start to reproduce before they optimize their DNA maintenance and repair, trading the benefits of earlier onset of reproduction against offspring mutation load. The increase in offspring mutation load with age likely represents germline senescence.

Parental age effects and Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, single factor analysis of variance (ANOVA), and multi-factor regression. No significant difference is observed in parental ages of RTT probands compared to that of the general population. A small increase in parental ages is observed in participants with missense variants compared to those with nonsense variants. When we evaluate the association between clinical severity and parental ages by multiple regression analysis, there is no clear association between clinical severity and parental ages. Advanced parental ages do not appear to be a risk factor for RTT, and do not contribute to the clinical severity in individuals with RTT.

Advanced parental age affects cardiometabolic risk in offspring.

Advanced age at conception usually refers to human mothers aged 35 years plus and fathers aged 40 years plus. Advanced parental age may be responsible for genetic and/or epigenetic alterations and may affect the health of offspring. Limited epidemiological and experimental studies have addressed the effect of advanced parental age on cardio-metabolic functions in human and rodent offspring. This mini review aimed to present the knowledge by focusing on adverse and favourable outcomes related to sex-specific risks and intergenerational inheritance. The outcomes identified by this review were mainly negative, but there were also some positive results.

Estimating the parental age effect on intelligence with controlling for confounding effects from genotypic differences

Estimating the parental age effect on intelligence with controlling for confounding effects from genotypic differences

Persistence of parental age effect on somatic mutation rates across generations in Arabidopsis

In the model plant Arabidopsis thaliana, parental age is known to affect somatic mutation rates in their immediate progeny and here we show that this age dependent effect persists across successive generations. Using a set of detector lines carrying the mutated uidA gene, we examined if a particular parental age maintained across five consecutive generations affected the rates of base substitution (BSR), intrachromosomal recombination (ICR), frameshift mutation (FS), and transposition. The frequency of functional GUS reversions were assessed in seedlings as a function of identical/different parental ages across generations. In the context of a fixed parental age, BSR/ICR rates were unaffected in the first three generations, then dropped significantly in the 4th and increased in most instances in the 5th generation (e.g. BSR (F1 38 = 0.9, F2 38 = 1.14, F3 38 = 1.02, F4 38 = 0.5, F5 38 = 0.76)). On the other hand, with advancing parental ages, BSR/ICR rates remained high in the first two/three generations, with a striking resemblance in the pattern of mutation rates (BSR (F1 38 = 0.9, F1 43 = 0.53, F1 48 = 0.79, F1 53 = 0.83 and F2 38 = 1.14, F2 43 = 0.57, F2 48 = 0.64, F2 53 = 0.94). We adopted a novel approach of identifying and tagging flowers pollinated on a particular day, thereby avoiding biases due to potential emasculation induced stress responses. Our results suggest a time component in counting the number of generations a plant has passed through self-fertilization at a particular age in determining the somatic mutation rates.

Effect of Parental Age, Parity, and Pairing Approach on Reproduction in Strain 13/N Guinea Pigs (Cavia porcellus)

Guinea pigs are important animal models for human disease, and both outbred and inbred lines are utilized in biomedical research. The optimal maintenance of guinea pig colonies, commercially and in research settings, relies on robust informed breeding programs, however, breeding data on specialized inbred strains are limited. Here, we investigated the effects of parental age, parity, and pairing approaches on mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days in strain 13/N guinea pigs. Our analysis of colony breeding data indicates that the average litter size is 3.3 pups, with a 25.2% stillbirth rate, a failure-to-thrive outcome in 5.1% of pups, and a 10 day survival rate of 69.7%. The only variable to significantly affect the reproductive outcomes examined was parental age (p < 0.05). In comparison to adults, both juvenile and geriatric sows had lower total fetus counts; juvenile boars had a higher percentage of females in litters, and geriatric boars had a lower 10 day survival rate of pups. These studies provide valuable information regarding the reproductive characteristics of strain 13/N guinea pigs, and support a variety of breeding approaches without significant effects on breeding success.

Limited role of generation time changes in driving the evolution of the mutation spectrum in humans.

Recent studies have suggested that the human germline mutation rate and spectrum evolve rapidly. Variation in generation time has been linked to these changes, though its contribution remains unclear. We develop a framework to characterize temporal changes in polymorphisms within and between populations, while controlling for the effects of natural selection and biased gene conversion. Application to the 1000 Genomes Project dataset reveals multiple independent changes that arose after the split of continental groups, including a previously reported, transient elevation in TCC>TTC mutations in Europeans and novel signals of divergence in C>Gand T>A mutation rates among population samples. We also find a significant difference between groups sampled in and outside of Africa in old T>C polymorphisms that predate the out-of-Africa migration. This surprising signal is driven by TpG>CpG mutations and stems in part from mis-polarized CpG transitions, which are more likely to undergo recurrent mutations. Finally, by relating the mutation spectrum of polymorphisms to parental age effects on de novo mutations, we show that plausible changes in the generation time cannot explain the patterns observed for different mutation types jointly. Thus, other factors - genetic modifiers or environmental exposures - must have had a non-negligible impact on the human mutation landscape.

Pediatric surgery and self-reported anxiety in children and their parents: A psychometric analysis of the state-trait operation anxiety (STOA) questionnaire.

The preoperative experience in pediatric surgery can cause significant anxiety for both, children and their parents. To date there is no questionnaire available that assesses the child's self-report or both, the child's and parent's self-reported anxiety. The aim of this study was to perform a psychometric analysis of the State-Trait Operation Anxiety (STOA) which provides this option. The data based on a randomized controlled study conducted with n = 90 child-parent dyads. The psychometric analyses were performed using classical test theory, including item statistics, Cronbach's α, factor analysis, and test-retest reliability. The statistics of the anxiety items were good overall for both ratings following common guidelines. The item means indicated that the items tended to be rather difficult which reduces the reliability for lower anxiety levels. The given scale structure was confirmed overall for both informants. However, a one-factor structure instead of two factors was found for state anxiety. The internal consistencies and retest reliabilities were good to very good. Follow-up analyses confirmed the sensitivity to change for state anxiety. Child anxiety was hardly correlated with parental anxiety, and age and gender effects were rather small. The STOA questionnaire is the first psychometrically tested questionnaire specifically for fears of surgery that can be used for self-report among children, adolescents, and their parents. Future studies should collect further evidence of its validity as well as comparative scores for specific patient groups and norm values to increase the utility of the instrument.

Effects of parental age on salt stress tolerance in an aquatic plant

Parental age influences components of offspring fitness in many species. The ability to tolerate stress also affects fitness, but less is known regarding changes in offspring stress tolerance with increasing parental age, especially in plants. We examined first and fifth‐born clonal offspring (using birth order as a proxy for parental age), and compared their fitness in several sub‐lethal concentrations of salt (NaCl), to investigate the interactive effects of birth order and salt stress on the offspring of the aquatic plant Lemna minor L. We found that increasing salt concentration reduced reproduction particularly at early ages, which detrimentally affected fitness, as measured by the intrinsic rate of natural increase. Fifth offspring had greater fitness than first offspring, potentially due to the hump‐shaped relationship between offspring fitness and birth order observed in other studies on Lemna, with fifth offspring near the peak of the hump. We found no interactive effect of birth order and salt concentration on offspring fitness; however, there were interactive effects on the time to first reproduction and the size of fronds. Specifically, first offspring exposed to increasing salt concentrations exhibited longer delays to first reproduction and grew to a greater size, while fifth offspring showed little change in either variable with increasing salt concentration. Thus, variation in birth order affected offspring response to salt stress, although not in terms of fitness. These results help illuminate factors impacting the age‐specific strength of natural selection and stress responses, and may be environmentally relevant in the context of environmental salinization.

Parental age at conception on mouse lemur's offspring longevity: Sex-specific maternal effects.

Parental age at conception often influences offspring's longevity, a phenomenon referred as the "Lansing effect" described in large variety of organisms. But, the majority of the results refer to the survival of juveniles, mainly explained by an inadequate parental care by the elderly parents, mostly the mothers. Studies on the effect of parental age on offspring's longevity in adulthood remain few, except in humans for whom effects of parental age vary according to statistical models or socioeconomic environments. In a small primate in which the longevity reaches up to 13 years, we investigated the effects of parental age at conception on the longevity of offspring (N = 278) issued from parents with known longevity. None of the postnatal parameters (body mass at 30 and 60 days after birth, size and composition of the litter) influenced offspring's longevity. Mothers' age at conception negatively affected offspring's longevity in males but not in females. By contrast, fathers' age at conception did not influence offspring's longevity. Finally, the longevity of female offspring was significantly positively related to the longevity of both parents. Compared with current studies, the surprisingly minor effect of fathers 'age was related to the high seasonal reproduction and the particular telomere biology of mouse lemurs.

Sex-dependent effects of parental age on offspring fitness in a cooperatively breeding bird.

Parental age can have considerable effects on offspring phenotypes and health. However, intergenerational effects may also have longer term effects on offspring fitness. Few studies have investigated parental age effects on offspring fitness in natural populations while also testing for sex- and environment-specific effects. Further, longitudinal parental age effects may be masked by population-level processes such as the selective disappearance of poor-quality individuals. Here, we used multigenerational data collected on individually marked Seychelles warblers (Acrocephalus sechellensis) to investigate the impact of maternal and paternal age on offspring life span and lifetime reproductive success. We found negative effects of maternal age on female offspring life span and lifetime reproductive success, which were driven by within-mother effects. There was no difference in annual reproductive output of females born to older versus younger mothers, suggesting that the differences in offspring lifetime reproductive success were driven by effects on offspring life span. In contrast, there was no association between paternal age and female offspring life span or either maternal or paternal age and male offspring life span. Lifetime reproductive success, but not annual reproductive success, of male offspring increased with maternal age, but this was driven by between-mother effects. No paternal age effects were found on female offspring lifetime reproductive success but there was a positive between-father effect on male offspring lifetime reproductive success. We did not find strong evidence for environment-dependent parental age effects. Our study provides evidence for parental age effects on the lifetime fitness of offspring and shows that such effects can be sex dependent. These results add to the growing literature indicating the importance of intergenerational effects on long-term offspring performance and highlight that these effects can be an important driver of variation in longevity and fitness in the wild.

Evidence of maternal and paternal age effects on speed in thoroughbred racehorses.

Effects of parental age on offspring viability have been reported in a wide range of species. However, to what extent parental age influences offspring traits beyond viability remains unclear. Moreover, previous research has primarily focused on maternal age effects. The purpose of this study was to test for paternal and maternal age effects on offspring speed in thoroughbred racehorses. We analysed over 900 000 race performances by over 100 000 horses on British racecourses between 1996 and 2019. With knowledge of the age of all 41 107 dams and 2 887 sires at offspring conception, we jointly modelled maternal and paternal age effects using a ‘within-individual centring’ approach. Within-parents, we identified a significant effect of maternal age on offspring speed of −0.017 yards s−1 yr−1 and a corresponding paternal age effect of −0.011 yards s−1 yr−1. Although maternal age effects were stronger (more negative), the existence and magnitude of paternal effects is particularly noteworthy, given thoroughbred sires have no involvement in parental care. Our results also suggest that the selective disappearance of both sires and dams is ongoing. These findings could potentially be used to optimize thoroughbred racehorse breeding decisions, and more generally, add to the increasing body of evidence that both maternal and paternal age affect a range of offspring characteristics.