Leukocyte Telomere Length and the Father's Age Enigma: Implications for Population Health and for Life Course

What are the implications for population health of the demographic trend toward increasing paternal age at conception (PAC) in modern societies? We propose that the effects of older PAC are likely to be broad and harmful in some domains of health but beneficial in others. Harmful effects of older PAC have received the most attention. Thus, for example, older PAC is associated with an increased risk of offspring having rare conditions such as achondroplasia and Marfan syndrome, as well as with neurodevelopmental disorders such as autism. However, newly emerging evidence in the telomere field suggests potentially beneficial effects, since older PAC is associated with a longer leukocyte telomere length (LTL) in offspring, and a longer LTL is associated with a reduced risk of atherosclerosis and with increased survival in the elderly. Thus, older PAC may cumulatively increase resistance to atherosclerosis and lengthen lifespan in successive generations of modern humans. In this paper we: (i) introduce these novel findings; (ii) discuss potential explanations for the effect of older PAC on offspring LTL; (iii) draw implications for population health and for life course; (iv) put forth an evolutionary perspective as a context for the multigenerational effects of PAC; and (v) call for broad and intensive research to understand the mechanisms underlying the effects of PAC. We draw together work across a range of disciplines to offer an integrated perspective of this issue

Can Sibling Sex Ratios Be Used as a Valid Test for the Prenatal Androgen Hypothesis of Autism Spectrum Disorders?

Sibling sex ratios have been applied as an indirect test of a hypothesized association between prenatal testosterone levels and risk for autism, a developmental disorder disproportionately affecting males. Differences in sibling sex ratios between those with and without autism would provide evidence of a shared risk factor for autism and offspring sex. Conclusions related to prenatal testosterone, however, require additional assumptions. Here, we used directed acyclic graphs (DAGs) to clarify the elements required for a valid test of the hypothesis that sibling sex ratios differ between children with and without autism. We then conducted such a test using a large, population-based sample of children

Fetal Environment and Schizophrenia

Schizophrenia and related disorders are adult-onset illnesses with no definitively established risk factors. Several studies report that exposures to infection and nutritional deprivation during early development may elevate the risk of later developing schizophrenia, specifically during the prenatal period. Preliminary evidence implicates lead exposure as well, suggesting that chemical exposures during early development may constitute a new class of risk factors for schizophrenia that has not been adequately investigated. Exposure to lead is given as an example of a chemical agent for which some effects have been described throughout the life course on both general neurodevelopmental outcomes and now on a specific psychiatric diagnosis. Findings from prospectively collected birth cohorts are offered as examples of both innovations in methodology and opportunities for future generations of investigators

Are social causes so different from all other causes? A comment on Sander Greenland

Sander Greenland's elegant paper raises deep questions about the way in which we choose and evaluate public health actions. We agree with the main thrust of his argument with respect to public health policy. We have some concerns, however, about his treatment of social causes, and on this point we focus our critique

Telomere Length and the Cancer–Atherosclerosis Trade-Off

Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan

Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California

The incidence and prevalence of autism have dramatically increased over the last 20 years. Decomposition of autism incidence rates into age, period and cohort effects disentangle underlying domains of causal factors linked to time trends. We estimate an age-period-cohort effect model for autism diagnostic incidence overall and by level of functioning

Severity and persistence of asthma and mental health: a birth cohort study

Background. The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link