Pregnancy is linked to faster epigenetic aging in young women.

A central prediction of evolutionary theory is that energy invested into reproduction comes at the expense of somatic maintenance and repair, accelerating biological aging. Supporting this prediction are findings that high fertility among women predicts shorter lifespan and poorer health later in life. However, biological aging is thought to begin before age-related health declines, limiting the applicability of morbidity and mortality for studying the aging process earlier in life. Here, we examine the relationship between reproductive history and biological aging in a sample of young (20 to 22yo) men and women from the Cebu Longitudinal Health and Nutrition Survey, located in the Philippines (n = 1,735). We quantify biological aging using six measures, collectively known as epigenetic clocks, reflecting various facets of cellular aging, health, and mortality risk. In a subset of women, we test whether longitudinal changes in gravidity between young and early-middle adulthood (25 to 31yo) are associated with changes in epigenetic aging during that time. Cross-sectionally, gravidity was associated with all six measures of accelerated epigenetic aging in women (n = 825). Furthermore, longitudinal increases in gravidity were linked to accelerated epigenetic aging in two epigenetic clocks (n = 331). In contrast, the number of pregnancies a man reported fathering was not associated with epigenetic aging among same-aged cohort men (n = 910). These effects were robust to socioecological, environmental, and immunological factors, consistent with the hypothesis that pregnancy accelerates biological aging and that these effects can be detected in young women in a high-fertility context.

Evidence for an adolescent sensitive period to family experiences influencing adult male testosterone production.

Across vertebrates, testosterone is an important mediator of reproductive trade-offs, shaping how energy and time are devoted to parenting versus mating/competition. Based on early environments, organisms often calibrate adult hormone production to adjust reproductive strategies. For example, favorable early nutrition predicts higher adult male testosterone in humans, and animal models show that developmental social environments can affect adult testosterone. In humans, fathers' testosterone often declines with caregiving, yet these patterns vary within and across populations. This may partially trace to early social environments, including caregiving styles and family relationships, which could have formative effects on testosterone production and parenting behaviors. Using data from a multidecade study in the Philippines (n = 966), we tested whether sons' developmental experiences with their fathers predicted their adult testosterone profiles, including after they became fathers themselves. Sons had lower testosterone as parents if their own fathers lived with them and were involved in childcare during adolescence. We also found a contributing role for adolescent father­son relationships: sons had lower waking testosterone, before and after becoming fathers, if they credited their own fathers with their upbringing and resided with them as adolescents. These findings were not accounted for by the sons' own parenting and partnering behaviors, which could influence their testosterone. These effects were limited to adolescence: sons' infancy or childhood experiences did not predict their testosterone as fathers. Our findings link adolescent family experiences to adult testosterone, pointing to a potential pathway related to the intergenerational transmission of biological and behavioral components of reproductive strategies.

Socioeconomic status is negatively associated with immunosenescence but positively associated with inflammation among middle-aged women in Cebu, Philippines.

BACKGROUND: Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity-an important contributor to chronic inflammation-might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines. METHODS: Data came from the mothers of the Cebu Longitudinal Health and Nutrition Survey birth cohort (mean age: 47.7, range: 35-69 years). SES was measured as a combination of annual household income, education level, and assets. Chronic inflammation was measured using C-reactive protein (CRP) in plasma samples from 1,834 women. Immunosenescence was measured by the abundance of exhausted CD8T (CD8 + CD28-CD45RA-) and naïve CD8T and CD4T cells, estimated from DNA methylation in whole blood in a random subsample of 1,028. Possible mediators included waist circumference and a collection of proxy measures of pathogen exposure. RESULTS: SES was negatively associated with the measures of immunosenescence, with slight evidence for mediation by a proxy measure for pathogen exposure from the household's drinking water source. In contrast, SES was positively associated with CRP, which was explained by the positive association with waist circumference. CONCLUSIONS: Similar to higher income populations, in Cebu there is an SES-gradient in pathogen exposures and immunosenescence. However, lifestyle changes occurring more rapidly among higher SES individuals is contributing to a positive association between SES and adiposity and inflammation. Our results suggest more studies are needed to clarify the relationship between SES and inflammation and immunosenescence across LMIC.

Intimate partner violence, depression, and chronic low-grade inflammation among middle-aged women in Cebu, Philippines.

OBJECTIVES: Recent discussions in human biology have highlighted how local ecological contexts shape the relationship between social stressors and health across populations. Chronic low-grade inflammation has been proposed as a pathway linking social stressors to health, with evidence concentrated in high-income Western contexts. However, it remains unclear whether this is an important pathway in populations where prevalence is lower due to lower adiposity and greater infectious exposures. To investigate this further, we tested associations between multiple types of intimate partner violence (IPV), a highly prevalent stressor and health crisis globally, and C-reactive protein (CRP), a commonly used measure of chronic low-grade inflammation, in Cebu, Philippines. For reference, we compared results for CRP to depression, a well-established and consistently observed health outcome of IPV. METHODS: Data came from 1601 currently partnered women (ages 35-69 years) as part of the Cebu Longitudinal Health and Nutrition Survey. IPV exposures included physical, emotional, and controlling behavior. Depression scores were measured using a modified version of the Center for Epidemiologic Studies-Depression Scale for this population, whereas plasma CRP was measured from overnight-fasted morning blood samples. RESULTS: All three types of IPV were associated with a higher depression score. However, none of the IPV measures were associated with CRP. In a post hoc interaction test, emotional IPV became positively associated with CRP as waist circumference increased above the mean. CONCLUSIONS: Our results suggest a complex relationship between social stressors and chronic low-grade inflammation, which is likely dependent on the population-specific context of lifestyle and environmental factors.

The human gut microbiome and health inequities.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.

Psychological legacies of intergenerational trauma under South African apartheid: Prenatal stress predicts greater vulnerability to the psychological impacts of future stress exposure during late adolescence and early adulthood in Soweto, South Africa.

BACKGROUND: South Africa's rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country's long history of political violence during apartheid. Growing evidence suggests that in utero stress exposure is a potent developmental risk factor for future mental illness risk, yet the extent to which the psychiatric effects of prenatal stress impact the next generation are unknown. We evaluate the intergenerational effects of prenatal stress experienced during apartheid on psychiatric morbidity among children at ages 17-18 and also assess the moderating effects of maternal age, social support, and past household adversity. METHODS: Participants come from Birth-to-Twenty, a longitudinal birth cohort study in Soweto-Johannesburg, South Africa's largest peri-urban township which was the epicentre of violent repression and resistance during the final years of the apartheid regime. Pregnant women were prospectively enrolled in 1990 and completed questionnaires assessing social experiences, and their children's psychiatric morbidity were assessed at ages 17-18. RESULTS: Full data were available from 304 mother-child pairs in 2007-8. Maternal prenatal stress in 1990 was not directly associated greater psychiatric morbidity during at ages 17-18. Maternal age and past household adversity moderated the intergenerational mental health effects of prenatal stress such that children born to younger mothers and late adolescent/young adult children experiencing greater household adversity exhibited worse psychiatric morbidity at ages 17-18. Social support did not buffer against the long-term psychiatric impacts of prenatal stress. CONCLUSIONS: Greater prenatal stress from apartheid predicted adverse psychiatric outcomes among children born to younger mothers and adolescents/young adults who experienced greater concurrent stress. Our findings suggest that prenatal stress may affect adolescent mental health, have stress-sensitising effects, and represent possible intergenerational effects of trauma experienced under apartheid in this sample.

Association between infectious exposures in infancy and epigenetic age acceleration in young adulthood in metropolitan Cebu, Philippines.

OBJECTIVES: The drivers of human life expectancy gains over the past 200 years are not well-established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation-based markers that forecast patterns of morbidity and mortality later in life. METHODS: N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey-a prospective birth cohort initiated in 1983-provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. RESULTS: Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. CONCLUSIONS: We document negative associations between measures of infectious exposure in infancy and DNA methylation-based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy.

Why do humans undergo an adiposity rebound? Exploring links with the energetic costs of brain development in childhood using MRI-based 4D measures of total cerebral blood flow.

BACKGROUND: Individuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain's energy requirements account for a lifetime peak of 66% of the body's resting metabolic expenditure during childhood, around the age of the AR, and relates inversely to weight gain, pointing to a potential energy trade-off between brain development and adiposity. However, no study has compared developmental trajectories of brain metabolism and adiposity in the same individuals, which would allow a preliminary test of a brain-AR link. METHODS: We used cubic splines and generalized additive models to compare age trajectories of previously collected MRI-based 4D flow measures of total cerebral blood flow (TCBF), a proxy for cerebral energy use, to the body mass index (BMI) in a cross-sectional sample of 82 healthy individuals (0-60 years). We restricted our AR analysis to pre-pubertal individuals (0-12 years, n = 42), predicting that peak TCBF would occur slightly after the BMI nadir, consistent with evidence that lowest BMI typically precedes the nadir in adiposity. RESULTS: TCBF and the BMI showed inverse trajectories throughout childhood, while the estimated age at peak TCBF (5.6 years) was close but slightly later than the estimated age of the BMI nadir (4.9 years). CONCLUSIONS: The timing of peak TCBF in this sample points to a likely concordance between peak brain energetics and the nadir in adiposity. Inverse age trajectories between TCBF and BMI support the hypothesis that brain metabolism is a potentially important influence on early life adiposity. These findings also suggest that experiences influencing the pattern of childhood brain energy use could be important predictors of body composition trajectories.

Neither environmental unpredictability nor harshness predict reliance on alloparental care among families in Cebu, Philippines.

Alloparental caregiving is key to humans' highly flexible reproductive strategies. Across species and across societies, alloparental care is more common in harsh and/or unpredictable environments (HUEs). Currently, however, it is unclear whether HUEs predict intra-population variation in alloparental care, or whether early life HUEs might predict later alloparental care use in adulthood, consistent with adaptive developmental plasticity. We test whether harshness measures (socioeconomic status (SES), environmental hygiene, crowding) and unpredictability measures (parental unemployment, paternal absence, household moves) predicted how much alloparental assistance families in Cebu, Philippines received, in a multigenerational study with data collected across four decades. Though worse environmental hygiene predicted more concurrent alloparental care in 1994, we found little evidence that HUEs predict within-population variation in alloparental care in this large-scale, industrialized society. Indeed, less-crowded conditions and higher SES predicted more alloparental care, not less, in the 1980s and in 2014 respectively, while paternal absence in middle childhood predicted less reliance on alloparental care in adulthood. In this cultural context, our results generally do not provide support for the translation of interspecific or intersocietal patterns linking HUEs and alloparental care to intra-population variation in alloparental care, nor for the idea that a reproductive strategy emphasizing alloparental care use may be preceded by early life HUEs.

A biosocial return to race? A cautionary view for the postgenomic era.

Recent studies demonstrating epigenetic and developmental sensitivity to early environments, as exemplified by fields like the Developmental Origins of Health and Disease (DOHaD) and environmental epigenetics, are bringing new data and models to bear on debates about race, genetics, and society. Here, we first survey the historical prominence of models of environmental determinism in early formulations of racial thinking to illustrate how notions of direct environmental effects on bodies have been used to naturalize racial hierarchy and inequalities in the past. Next, we conduct a scoping review of postgenomic work in environmental epigenetics and DOHaD that looks at the role of race/ethnicity in human health (2000-2021). Although there is substantial heterogeneity in how race is conceptualized and interpreted across studies, we observe practices that may unwittingly encourage typological thinking, including: using DNA methylation as a novel marker of racial classification; neglect of variation and reversibility within supposedly homogenous racial groups; and a tendency to label and reify whole groups as pathologized or impaired. Even in the very different politico-economic and epistemic context of contemporary postgenomic science, these trends echo deeply held beliefs in Western thinking which claimed that different environments shape different bodies and then used this logic to argue for essential differences between Europeans and non-Europeans. We conclude with a series of suggestions on interpreting and reporting findings in these fields that we feel will help researchers harness this work to benefit disadvantaged groups while avoiding the inadvertent dissemination of new and old forms of stigma or prejudice.

A hypothesis linking the energy demand of the brain to obesity risk.

The causes of obesity are complex and multifactorial. We propose that one unconsidered but likely important factor is the energetic demand of brain development, which could constrain energy available for body growth and other functions, including fat deposition. Humans are leanest during early childhood and regain body fat in later childhood. Children reaching this adiposity rebound (AR) early are at risk for adult obesity. In aggregate data, the developing brain consumes a lifetime peak of 66% of resting energy expenditure in the years preceding the AR, and brain energy use is inversely related to body weight gain from infancy until puberty. Building on this finding, we hypothesize that individual variation in childhood brain energy expenditure will help explain variation in the timing of the AR and subsequent obesity risk. The idea that brain energetics constrain fat deposition is consistent with evidence that genes that elevate BMI are expressed in the brain and mediate a trade-off between the size of brain structures and BMI. Variability in energy expended on brain development and function could also help explain widely documented inverse relationships between the BMI and cognitive abilities. We estimate that variability in brain energetics could explain the weight differential separating children at the 50th and 70th BMI-for-age centiles immediately before the AR. Our model proposes a role for brain energetics as a driver of variation within a population's BMI distribution and suggests that educational interventions that boost global brain energy use during childhood could help reduce the burden of obesity.

Evidence that prenatal testosterone transfer from male twins reduces the fertility and socioeconomic success of their female co-twins.

During sensitive periods in utero, gonadal steroids help organize biological sex differences in humans and other mammals. In litter-bearing species, chromosomal females passively exposed to prenatal testosterone from male littermates exhibit altered physical and behavioral traits as adults. The consequences of such effects are less well understood in humans, but recent near-doubling of twinning rates in many countries since 1980, secondary to advanced maternal age and increased reliance on in vitro fertilization, means that an increasing subset of females in many populations may be exposed to prenatal testosterone from their male co-twin. Here we use data on all births in Norway (n = 728,842, including 13,800 twins) between 1967 and 1978 to show that females exposed in utero to a male co-twin have a decreased probability of graduating from high school (15.2%), completing college (3.9%), and being married (11.7%), and have lower fertility (5.8%) and life-cycle earnings (8.6%). These relationships remain unchanged among the subsets of 583 and 239 females whose male co-twin died during the first postnatal year and first 28 days of life, respectively, supporting the interpretation that they are due primarily to prenatal exposure rather than to postnatal socialization effects of being raised with a male sibling. Our findings provide empirical evidence, using objectively measured nation-level data, that human females exposed prenatally to a male co-twin experience long-term changes in marriage, fertility, and human capital. These findings support the hypothesis of in utero testosterone transfer between twins, which is likely affecting a small but growing subset of females worldwide.

Group structure, but not dominance rank, predicts fecal androgen metabolite concentrations of wild male mountain gorillas (Gorilla beringei beringei).

Androgens are important mediators of male-male competition in many primate species. Male gorillas' morphology is consistent with a reproductive strategy that relies heavily on androgen-dependent traits (e.g., extreme size and muscle mass). Despite possessing characteristics typical of species with an exclusively single-male group structure, multimale groups with strong dominance hierarchies are common in mountain gorillas. Theory predicts that androgens should mediate their dominance hierarchies, and potentially vary with the type of group males live in. We validated the use of a testosterone enzyme immunoassay (T-EIA R156/7, CJ Munro, UC-Davis) for use with mountain gorilla fecal material by (1) examining individual-level androgen responses to competitive events, and (2) isolating assay-specific hormone metabolites via high-performance liquid chromatography. Males had large (2.6- and 6.5-fold), temporary increases in fecal androgen metabolite (FAM) after competitive events, and most captured metabolites were testosterone or 5α-dihydrotestosterone-like androgens. We then examined the relationship between males' dominance ranks, group type, and FAM concentrations. Males in single-male groups had higher FAM concentrations than males in multimale groups, and a small pool of samples from solitary males suggested they may have lower FAM than group-living peers. However, data from two different time periods (n = 1610 samples) indicated there was no clear relationship between rank and FAM concentrations, confirming results from the larger of two prior studies that measured urinary androgens. These findings highlight the need for additional research to clarify the surprising lack of a dominance hierarchy/androgen relationship in mountain gorillas.

Germline epigenetic inheritance: Challenges and opportunities for linking human paternal experience with offspring biology and health.

Recently, novel experimental approaches and molecular techniques have demonstrated that a male's experiences can be transmitted through his germline via epigenetic processes. These findings suggest that paternal exposures influence phenotypic variation in unexposed progeny-a proposal that runs counter to canonical ideas about inheritance developed during the 20th century. Nevertheless, support for paternal germline epigenetic inheritance (GEI) in nonhuman mammals continues to grow and the mechanisms underlying this phenomenon are becoming clearer. To what extent do similar processes operate in humans, and if so, what are their implications for understanding human phenotypic variation, health, and evolution? Here, we review evidence for GEI in human and nonhuman mammals and evaluate these findings in relation to historical conceptions of heredity. Drawing on epidemiological data, reproductive biology, and molecular embryology, we outline developments and opportunities for the study of GEI in human populations, emphasizing the challenges that researchers in this area still face.

The development of executive function in early childhood is inversely related to change in body mass index: Evidence for an energetic tradeoff?

A well-established literature demonstrates executive function (EF) deficits in obese children and adults relative to healthy weight comparisons. EF deficits in obesity are associated with overeating and impulsive consumption of high calorie foods leading to excess weight gain and to problems with metabolic regulation and low-grade inflammation that detrimentally affect the structure and function of prefrontal cortex. Here, we test a complementary explanation for the relation between EF and body mass index (BMI) grounded in the energy demand of the developing brain. Recent work shows that the brain accounts for a lifetime peak of 66% of resting metabolic rate in childhood and that developmental changes in brain energetics and normative changes in body weight gain are closely inversely related. This finding suggests a trade-off in early childhood between energy used to support brain development versus energy used to support physical growth and fat deposition. To test this theorized energetic trade-off, we analyzed data from a large longitudinal sample (N = 1,292) and found that change in EF from age 3 to 5 years, as a proxy for brain development in energetically costly prefrontal cortex, is inversely related to change in BMI from age 2 to 5 years. Greater linear decline in BMI predicted greater linear increase in EF. We interpret this finding as tentative support for a brain-body energetic trade-off in early childhood with implications for lifetime obesity risk.

Early life stress and HPA axis function independently predict adult depressive symptoms in metropolitan Cebu, Philippines.

OBJECTIVES: Alterations in adult hypothalamic-pituitary-adrenal (HPA) axis activity have increasingly been linked with early life stress and adult depression, but a limited number of studies have used longitudinal data to explore HPA axis dysregulation as an underlying mechanism driving the long-term depressive impacts of early stressors. Here we address potential long-term impacts of early life, family-based stress on depressive symptoms among young adults in a longitudinal birth cohort study begun in 1983 in the Philippines. MATERIALS AND METHODS: We relate a composite measure of family-based stressors experienced between birth and adolescence to circadian dynamics in adult salivary cortisol and depressive risk measured at 21-22 years of age. Multiple regression analyses were conducted to examine the relationship between early life stress levels and risk of adult depressive symptoms, as well as the role of adult diurnal cortisol activity in this relationship. RESULTS: Greater levels of early life familial stress predicted more severe depressive symptomatology at age 21-22 in a dose-response fashion (p < .0001) independent of adult diurnal cortisol patterns. Flatter diurnal cortisol slopes are directly associated with higher adult depressive symptoms, an effect mostly driven by evening cortisol levels (p = .004). When considering the cumulative effects of early life stress measures, however, exposure to more of these stressors during development is associated with even higher depressive symptoms. DISCUSSION: The long-term depressive effects of early life familial stress extend to this large sample of Cebuano young adults, and early life stress and HPA axis function may shape adult depressive symptoms through independent pathways in this sample. Our findings provide further evidence that HPA axis activity is shaped by early life conditions and is associated with depressive symptoms.

Testing for paternal influences on offspring telomere length in a human cohort in the Philippines.

OBJECTIVES: Telomeres, emerging biomarkers of aging, are comprised of DNA repeats located at chromosomal ends that shorten with cellular replication and age in most human tissues. In contrast, spermatocyte telomeres lengthen with age. These changes in telomere length (TL) appear to be heritable, as older paternal ages of conception (PAC) predict longer offspring TL. Mouse-model studies raise questions about the potential for effects of paternal experiences on human offspring TL, as they suggest that smoking, inflammation, DNA damage, and stressors all shorten sperm TL. Here, we examined whether factors from the paternal environment predict offspring TL as well as interact with PAC to predict offspring TL. MATERIALS AND METHODS: Using data from the Philippines, we tested if smoking, psychosocial stressors, or shorter knee height (a measure of early life adversity) predict shorter offspring TL. We also tested if these interacted with PAC in predicting offspring TL. RESULTS: While we did not find the predicted associations, we observed a trend toward fathers with shorter knee height having offspring with longer TL. In addition, we found that knee height interacted with PAC to predict offspring TL. Specifically, fathers with shorter knee heights showed a stronger positive effect of PAC on offspring TL. DISCUSSION: While the reasons for these associations remain uncertain, shorter knee height is characteristic of earlier puberty. Since spermatocyte TL increases with the production of sperm, we speculate that individuals with earlier puberty, and its concomitant commencement of production of sperm, had more time to accumulate longer sperm telomeres.

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood.

Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a population-based longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20-22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.

Evolutionary life history theory as an organising framework for cohort studies: insights from the Cebu Longitudinal Health and Nutrition Survey.

By tracking a group of individuals through time, cohort studies provide fundamental insights into the developmental time course and causes of health and disease. Evolutionary life history theory seeks to explain patterns of growth, development, reproduction and senescence, and inspires a range of hypotheses that are testable using the longitudinal data from cohort studies. Here we review two decades of life history theory-motivated work conducted in collaboration with the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a birth cohort study that enrolled more than 3000 pregnant women in the Philippines in 1983 and has since followed these women, their offspring and grandoffspring. This work has provided evidence that reproduction carries "costs" to cellular maintenance functions, potentially speeding senescence, and revealed an unusual form of genetic plasticity in which the length of telomeres inherited across generations is influenced by reproductive timing in paternal ancestors. Men in Cebu experience hormonal and behavioural changes in conjunction with changes in relationship and fatherhood status that are consistent with predictions based upon other species that practice bi-parental care. The theoretical expectation that early life cues of mortality or environmental unpredictability will motivate a "fast" life history strategy are confirmed for behavioural components of reproductive decision making, but not for maturational tempo, while our work points to a broader capacity for early life developmental calibration of systems like immunity, reproductive biology and metabolism. Our CLHNS findings illustrate the power of life history theory as an integrative, lifecourse framework to guide longitudinal studies of human populations.

Older paternal ages and grandpaternal ages at conception predict longer telomeres in human descendants.

Telomere length (TL) declines with age in most human tissues, and shorter TL appears to accelerate senescence. By contrast, men's sperm TL is positively correlated with age. Correspondingly, in humans, older paternal age at conception (PAC) predicts longer offspring TL. We have hypothesized that this PAC effect could persist across multiple generations, and thereby contribute to a transgenerational genetic plasticity that increases expenditures on somatic maintenance as the average age at reproduction is delayed within a lineage. Here, we examine TL data from 3282 humans together with PAC data across four generations. In this sample, the PAC effect is detectable in children and grandchildren. The PAC effect is transmitted through the matriline and patriline with similar strength and is characterized by a generational decay. PACs of more distant male ancestors were not significant predictors, although statistical power was limited in these analyses. Sensitivity analyses suggest that the PAC effect is linear, not moderated by offspring age, or maternal age, and is robust to controls for income, urbanicity and ancestry. These findings show that TL reflects the age at the reproduction of recent male matrilineal and patrilineal ancestors, with an effect that decays across generations.