DNA methylation age is associated with mortality in a longitudinal Danish twin study

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30–82 years, and furthermore included a 10‐year longitudinal study of the 86 oldest‐old twins (mean age of 86.1 at follow‐up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4–77%) increased mortality risk for each 5‐year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more‐than‐double mortality risk for the DNAm oldest twin compared to the co‐twin and a ‘dose–response pattern’ with the odds of dying first increasing 3.2 (1.05–10.1) times per 5‐year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest‐old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging.     

Reexamination of paternal age effect in Down's syndrome

Summary The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47,+21 cases was studied. The mean paternal age was 0.16 year greater than in the entire population of live births after controlling for maternal age. There was no evidence for a significant paternal age effect at the 0.05 level. For 242 of these Down's syndrome cases, control subjects were selected by rigidly matching in a systematic manner. Paternal age was the variable studied, with maternal age and time and place of birth controlled. There was no statistically significant association between paternal age and Down's syndrome. After adjustment for maternal age, these two studies were not consistent with an increase of paternal age in Down's syndrome.     

Spontaneous mutation and parental age in humans.

A statistical analysis of parental age and the incidence of new mutation has been performed. Some new data on Apert, Crouzon, and Pfeiffer syndromes is presented and combined with all available data from the literature on parental age and new mutation. Significant heterogeneity among syndromes for the rate of increase in incidence with parental age was found. A parsimonious conclusion is that mutations fall into two groups, one with a high rate of increase with age and the other with a low rate of increase with age. For the high-rate-of-increase group, a linear model relating incidence to age is rejected, while an exponential model is not. In addition, for this group, increased paternal age cannot account for the observed increase in maternal age--that is, increased maternal age also contributes to the incidence of new mutations. For the low-rate-of-increase group, increased paternal age alone can account for the observed increase in maternal ages; also, either a linear or exponential model is acceptable. In addition, there is no evidence for a mixture of parental age-independent cases with parental age-dependent cases for any of the syndromes examined. The curves reflecting incidence of new mutation and paternal age for two syndromes, Apert and neurofibromatosis, have an anomalous shape. In both cases the curve increases up to age 37 and drops at age 42 before increasing again at age 47. The usual explanation for the effect of parental age on new mutations is the mechanism of "copy-error" at mitotic division in male sperone that specifies an increased probability of mutation with time spent by a spermatozoon or ovum in a haploid state, a period of time that may also increase with age of the parent. A firm answer to the question of parental age and new mutation awaits identification of the molecular defect underlying some of these syndromes; we will then be in a position to determine in which parent the mutation occurred and at what age it did so.     

Age paternel: apport des données épidémiologiques et d'AMP

Introduction

Maternal age over 35 years is a well known risk factor in reproduction. This effect of maternal age had been demonstrated on the risk of infertility and the risk of miscarriage on the basis of epidemiological data and ART data, especially AID sources. In contrast, the effect of paternal age has been rarely analysed. The objective of this study was to review the literature analysing the effect of paternal age on the risk of infertility and the risk of miscarriage.

Material and method

Sixteen publications analysing paternal age were selected by a MEDLINE search. Thirteen publications concerned epidemiological data, based on surveys in the general population, surveys in pregnant women, case-control studies, and birth and death certificates. Three publications concerned ART data, based on IVF with ovum donation. In IVF with ovum donation, there is no correlation between paternal age and age of the female gamete donor.

Results

Seven epidemiological studies analysed the effect of paternal age on the risk of infertility. After controlling for maternal age, five studies showed a paternal age effect, and one showed a very weak paternal age effect. The last study did not show any paternal age effect, but only considered men under the age of 33 years. Three studies analysed the effect of paternal age on pregnancy rates in IVF with ovum donation. Only one study showed a paternal age effect. The four studies analysing the effect of paternal age on the risk of miscarriage showed a paternal age effect and two of the three studies based on birth and death certificates showed a paternal age effect on late foetal death (>20 weeks of gestation).

Conclusion

There are concordant data in the literature showing an effect of paternal age on the risk of infertility and the risk of miscarriage. Paternal age over 40 years could therefore be a risk factor in reproduction in the same way as maternal age over 35 years. Moreover, the risk of infertility and the risk of miscarriage could be much higher when both partners are over the age of 35–40 years.     

Social and biological determinants of age at first marriage in Taiwan, 1970

Abstract

This study examines the social and biological determinants of age at first marriage in two townships in northern Taiwan, one very rural and traditional and the other urban and modernized. For a sample of 5,707 once‐married women a path analysis was performed in which age at first marriage was considered a function of age, educational attainment, urban origin, premarital labor‐force participation, and age at menarche. Age at menarche, with a positive effect on the dependent variable, was the most important direct cause of age at first marriage. Although exogenous variables associated with modernization (urban origin, educational attainment and younger age) had a positive direct effect on age at first marriage, they also had a negative indirect effect on age at first marriage through their negative direct effect on age at menarche.     

松嫩平原杂类草草甸阿尔泰狗哇花无性系种群构件年龄结构

阿尔泰狗哇花为根蘖型菊科多年生无性系草本植物.采用主根芽区的繁殖世代数划分分株和芽龄级的方法,研究了松嫩平原杂类草草甸阿尔泰狗哇花无性系种群不同构件的年龄结构.结果表明:分株构件和芽构件均由4个龄级组成.在孕蕾期,分株构件中1龄级占22.6%、2龄级44.8%、3龄级28.8%、4龄级3.8%,呈稳定型年龄结构.在乳熟期,生殖分株构件以2龄级比重最大,占45.6%,4龄级最小,占0.8%,为稳定型年龄结构;而营养分株构件以1龄级比重最大,占47.5%,4龄级最小,占1.1%,为增长型年龄结构.分株主根的生活年限最多为5年.不同生育期分株构件的生产力均以2龄级最高.在乳熟期,1龄级分株具有较大的生产潜力,4龄级分株的生产力已普遍减弱.芽库中潜在种群呈增长型年龄结构.     

Naturally occurring genetic variation in the age-specific immune response of Drosophila melanogaster

Immunosenescence, the age‐related decline in immune response, is a well‐known consequence of aging. To date, most studies of age‐related changes in immune response focused on the cellular and physiological bases of this decline; we have virtually no understanding of the genetic basis of age‐related changes in the immune system or if indeed such control exists. We used 25 chromosome substitution lines of Drosophila melanogaster derived from a natural population to address three questions: (i) How is the function of the innate immune system influenced by age? (ii) Is there a genetic basis for phenotypic variation in immune response at different ages? (iii) Is there a genetic basis for differences in the way that age influences the immune function? Virgin females from each line were assayed for immune response using clearance of infection with Escherichia coli at 1 and 4 weeks of age. We found significant genetic variation among lines in immune response at each age. Unexpectedly, when averaged across all lines, the immune response actually improved with age. However, there was significant variation in the effect of age on immune response with 11 lines showing improvement, nine lines showing no change and five exhibiting a decline with age. There was no genetic correlation of immune response across ages suggesting that different loci contribute to variation in immune response at each age. The genetic component of the variation in immune response increased with age, a pattern predicted by the mutation accumulation model of senescence. However, this increase in variation resulted in part from the improvement of the immune response in some lines with age. Thus the observed changes in genetic variation in immune function with age are not entirely explained by the mutation accumulation model.     

Assessment of development of the testes and accessory glands by ultrasonography in bull calves and associated endocrine changes

The testes, prostate and vesicular glands of 10 bull calves were examined by ultrasonography every 2 wk from 2 to 46 wk of age, at which time the scrotal circumference (SC) of all the calves had reached pubertal size (28 cms). Computer-assisted image intensity analysis (numerical pixel values) was conducted. Blood samples were collected every other week from 2 to 46 wk of age. Testicular diameter increased in a linear manner from 2 to 46 wk of age, but the diameter measured in a transverse plane (caudal) was greater between 10 and 34 wk of age than when measured in a longitudinal (lateral) plane (P<0.05). Growth of the prostate and vesicular glands, based on dimensions, was linear, but vesicular gland length increased more rapidly after 32 wk of age (P<0.05). Image intensity of the vesicular glands and prostate declined from birth or 8 wk of age, respectively, to 14 wk of age, increased to 18 wk and then declined to a nadir at 30 wk, followed by a rapid increase to 34 wk of age for the vesicular glands and to 46 wk of age for the prostate (P<0.05). Image intensity of the testes showed an early increase to 6 to 8 wk of age and a subsequent increase from about 20 wk of age to 46 wk of age, with an inflection at 30 wk of age (P<0.05). There was a transient increase in mean serum concentrations of LH between 6 and 20 wk of age (P<0.05), and LH concentrations appeared to increase again after 36 wk of age (P>0.05). Mean serum concentrations of FSH declined with age (P<0.05). Mean serum concentrations of testosterone increased after 32 wk of age (P<0.05) In summary, numerical pixel values comprising the ultrasound images of the developing testes, prostate and vesicular glands revealed a complex development pattern that may reflect important details of developmental stages.     

Epigenetic predictor of age

From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age in saliva of 34 male identical twin pairs between 21 and 55 years of age. Furthermore, we validated sites in the promoters of three genes and replicated our results in a general population sample of 31 males and 29 females between 18 and 70 years of age. The methylation of three sites--in the promoters of the EDARADD, TOM1L1, and NPTX2 genes--is linear with age over a range of five decades. Using just two cytosines from these loci, we built a regression model that explained 73% of the variance in age, and is able to predict the age of an individual with an average accuracy of 5.2 years. In forensic science, such a model could estimate the age of a person, based on a biological sample alone. Furthermore, a measurement of relevant sites in the genome could be a tool in routine medical screening to predict the risk of age-related diseases and to tailor interventions based on the epigenetic bio-age instead of the chronological age.     

The Sensitivity of the Stationary Age Class Distribution o Changes in the Life History Components

The influence of the various components of the life history on the stationary age class distribution of a population was studied by applying the Leslie matrix model and then considering the single age class frequencies as well as the average age and the cumulative age class distribution in the stationary state. Since, for fixed survival probabilities, the effects of the (age specific) fecundities were shown to be already expressed by the (ultimate) growth rate, this investigation was concentrated on the influence of the survival probabilities and the growth rate. After having supplemented some useful details concerning the dependence of the growth rate on the life history and introduction of the shift concept as an interpretation of cumulative distributions, the mathematical results could be given a biologically intelligible meaning: An increase in the growth rate for fixed survival probabilities is followed by a shift of all age class frequencies to earlier ages. Whereas age specific changes in fecundity do not result in age specific changes in the stationary age class distribution, increases in survival up to and including age k, say, do exhibit such changes in that they cause a shift of age class frequencies at least from those ages exceeding k to earlier ages.     

Analysis of Nonlinear Gene Expression Progression Reveals Extensive Pathway and Age-Specific Transitions in Aging Human Brains

Several recent gene expression studies identified hundreds of genes that are correlated with age in brain and other tissues in human. However, these studies used linear models of age correlation, which are not well equipped to model abrupt changes associated with particular ages. We developed a computational algorithm for age estimation in which the expression of each gene is treated as a dichotomized biomarker for whether the subject is older or younger than a particular age. In addition, for each age-informative gene our algorithm identifies the age threshold with the most drastic change in expression level, which allows us to associate genes with particular age periods. Analysis of human aging brain expression datasets from three frontal cortex regions showed that different pathways undergo transitions at different ages, and the distribution of pathways and age thresholds varies across brain regions. Our study reveals age-correlated expression changes at particular age points and allows one to estimate the age of an individual with better accuracy than previously published methods.     

Flower production in relation to individual plant age and leaf production among different patches of Corydalis intermedia

The life history of an organism can be viewed as the combination of allocations made to maintenance, growth, and reproduction. Allocation to these functions are constrained by trade-offs as increased investment to one function may happen at the expense of another. Moreover, because fecundity and survival probabilities are affected by both the state of an individual and by its surrounding environment, optimal allocation to reproduction and growth may vary with both individual size/age and with the habitat in which it lives. In this study we aim to describe how flower production varies with individual plant age and leaf production among different patches of the perennial herb Corydalis intermedia. We take advantage of the construction of the underground storage organ to estimate the age of individual plants which allows us tacitly to relate flower and leaf production to individual age and successional status of the patch. We sampled all individuals present in nine patches from the same forest and estimated their age, flower production and total leaf area. The age distributions showed that each patch was most often dominated by a few and consecutive age classes. In patches where individuals had the oldest mean age, very few or no juvenile age classes were found suggesting that recruitment had ceased. Based on the age distribution of the patches we propose that the dynamics may best be described as metapopulational with colonization of newly formed open forest gaps and a successionally determined extinction as the patch gradually becomes too shaded for recruitment. Both mean flower production, leaf area and age varied significantly among patches. Flower production increased with both increasing age and leaf area. We found no indication of a trade off between reproduction and vegetative growth since flower production showed a positive relation with leaf production even after removing the effect of age. Number of flowers produced by plants of the same age but growing in different patches did not vary indicating that the difference among patches mainly was due to a difference in age distribution. No individuals produced flowers before they reached an estimated age of three years. Production of flowers followed a power function with increasing age. Our data suggests that C. intermedia plants change their allocation strategy with age investing a relatively large amount of energy in flower production immediately after the immature growth phase when recruitment in their patch may be high. Production of flowers then reaches a plateau around the age of 11 years after which number of flowers produced stays constant. This revised version was published online in June 2006 with corrections to the Cover Date.     

Menarcheal age and subsequent patterns of family formation

We examine whether age at menarche affects age at first marriage or first birth using two samples of U.S. women. Data are drawn from the Tremin Trust, a longitudinal study of menstrual cycles that recruited white women who were students at the University of Minnesota and from a survey of a nationally representative sample of white women born between 1900 and 1910. Regression models with cubic splines were used to analyze the relationship between age at menarche and age at first marriage. Cox proportional hazard models were used to examine the effect of age at menarche on the interval between marriage and first birth. Unlike earlier work, we found that once secular trends in both age at marriage and age at menarche were taken into account, there was no evidence that age at menarche affects either age at marriage or the timing of first births in these U.S. women.     

Extra structurally abnormal chromosomes (ESAC) detected at amniocentesis: frequency in approximately 75,000 prenatal cytogenetic diagnoses and associations with maternal and paternal age.

We analyzed rates of extra structurally abnormal chromosomes (ESAC) detected in prenatal cytogenetic diagnoses of amniotic fluid reported to the New York Chromosome Registry. These karyotypes include both extra unidentified structurally abnormal chromosomes (EUSAC)--often denoted as "markers"--and extra identified structurally abnormal chromosomes (EISAC). The rate of all EUSAC was 0.64/1,000 (0.32-0.40/1,000 mutant and 0.23-0.32 inherited), and that of all EISAC was 0.11/1,000 (0.07/1,000 mutant and 0.04/1,000 inherited). The rate of all ESAC was approximately 0.8/1,000-0.4-0.5/1,000 mutant and 0.3-0.4/1,000 inherited. Mean +/- SD maternal age of mutant cases was 37.5 +/- 2.9, significantly greater than the value of 35.8 years in controls. A regression analysis indicated a rate of change of the log of the rate of about +0.20 with each year of maternal age between 30 and 45 years. When paternal age was introduced, the maternal age coefficient increased to about +0.25--close to that seen for 47, +21--but the paternal age coefficient was -0.06. After being matched for maternal age and year of diagnosis, the case-control difference in paternal age for 24 mutant cases was -2.4 with a 95% confidence interval of -4.6 to -0.1 years. In a regression analysis of the effects of both parental ages on the (log) rate, the maternal age coefficient was +0.25 and the paternal age coefficient was -0.06. These results are consistent with a (weak) negative paternal age effect in the face of a strong maternal age effect. Since ESAC include a heterogeneous group of abnormalities, the maternal age and paternal age trends, if not the result of statistical fluctuation or undetected biases, may involve different types of events. Data in the literature suggest that chromosomes with de novo duplicated inversions of 15p have a strong maternal age effect (but little paternal age effect). Such chromosomes, however, do not account for the active maternal age trends seen in the data analyzed here. Inherited ESAC exhibited no such trends.     

Epigenetic estimation of age in humpback whales

Age is a fundamental aspect of animal ecology, but is difficult to determine in many species. Humpback whales exemplify this as they have a lifespan comparable to humans, mature sexually as early as 4 years and have no reliable visual age indicators after their first year. Current methods for estimating humpback age cannot be applied to all individuals and populations. Assays for human age have recently been developed based on age‐induced changes in DNA methylation of specific genes. We used information on age‐associated DNA methylation in human and mouse genes to identify homologous gene regions in humpbacks. Humpback skin samples were obtained from individuals with a known year of birth and employed to calibrate relationships between cytosine methylation and age. Seven of 37 cytosines assayed for methylation level in humpback skin had significant age‐related profiles. The three most age‐informative cytosine markers were selected for a humpback epigenetic age assay. The assay has an R² of 0.787 (P = 3.04e?16) and predicts age from skin samples with a standard deviation of 2.991 years. The epigenetic method correctly determined which of parent–offspring pairs is the parent in more than 93% of cases. To demonstrate the potential of this technique, we constructed the first modern age profile of humpback whales off eastern Australia and compared the results to population structure 5 decades earlier. This is the first epigenetic age estimation method for a wild animal species and the approach we took for developing it can be applied to many other nonmodel organisms.     

Epigenetic age is a cell‐intrinsic property in transplanted human hematopoietic cells

The age of tissues and cells can be accurately estimated by DNA methylation analysis. The multitissue DNA methylation (DNAm) age predictor combines the DNAm levels of 353 CpG dinucleotides to arrive at an age estimate referred to as DNAm age. Recent studies based on short‐term observations showed that the DNAm age of reconstituted blood following allogeneic hematopoietic stem cell transplantation (HSCT) reflects the age of the donor. However, it is not known whether the DNAm age of donor blood remains independent of the recipient's age over the long term. Importantly, long‐term studies including child recipients have the potential to clearly reveal whether DNAm age is cell‐intrinsic or whether it is modulated by extracellular cues in vivo. Here, we address this question by analyzing blood methylation data from HSCT donor and recipient pairs who greatly differed in chronological age (age differences between 1 and 49 years). We found that the DNAm age of the reconstituted blood was not influenced by the recipient's age, even 17 years after HSCT, in individuals without relapse of their hematologic disorder. However, the DNAm age of recipients with relapse of leukemia was unstable. These data are consistent with our previous findings concerning the abnormal DNAm age of cancer cells, and it can potentially be exploited to monitor the health of HSCT recipients. Our data demonstrate that transplanted human hematopoietic stem cells have an intrinsic DNAm age that is unaffected by the environment in a recipient of a different age.     

How Old Do You Feel? The Role of Age Discrimination and Biological Aging in Subjective Age

Subjective age, or how young or old individuals experience themselves to be relative to their chronological age, is a crucial construct in gerontology. Subjective age is a significant predictor of important health outcomes, but little is known about the criteria by which individuals'' subjectively evaluate their age. To identify psychosocial and biomedical factors linked to the subjective evaluation of age, this study examined whether perceived age discrimination and markers of biological aging are associated with subjective age. Participants were 4776 adults (M _age = 68) from the 2008 and 2010 waves of the Health and Retirement Study (HRS) who completed measures of subjective age, age discrimination, demographic variables, self-rated health and depression, and had physical health measures, including peak expiratory flow, grip strength, waist circumference, systolic and diastolic blood pressure. Telomere length was available for a subset of participants in the 2008 wave (n = 2214). Regression analysis indicated that perceived age discrimination, lower peak expiratory flow, lower grip strength, and higher waist circumference were associated with an older subjective age, controlling for sociodemographic factors, self-rated health, and depression. In contrast, blood pressure and telomere length were not related to subjective age. These findings are consistent with the hypothesis that how old a person feels depends in part on psychosocial and biomedical factors, including the experiences of ageism and perceptible indices of fitness and biological age.     

Universal sex differences in online advertisers age preferences: comparing data from 14 cultures and 2 religious groups

The search for a potential partner has been aided over recent years by the widespread use of online dating sites and this process of relationship formation has conveniently presented an ideal opportunity for researchers to analyze human mating desires and to compare evolutionary and social constructivist based hypotheses. One such aspect of human mating behaviour yet to be thoroughly explored using access to online dating advertisements is the idealized age desired by each sex when considering a possible relationship. This study accessed minimum (youngest age considered) and maximum (oldest age considered) age preferences from 14 separate cultures and two religious groups from both sexes at ages 20, 25, 30, 35, 40, 45, and 50 years. The results showed that overall there was a growing disparity between males own age and preferred age of partner as males themselves aged (as indicated by greater effect sizes with advertisers age), with females showing a pattern for preferences around their own age or older. Females did not express an age preference for males younger than male's age preferences for females at any advertiser's age. On only three occasions were there no age differences between the sexes in their desire to initiate a relationship with the opposite sex. The results were clearly concurrent with earlier findings supportive of evolutionary or adaptationist interpretations. Neither a random pattern of age preferences more consistent with an arbitrary norms prediction, nor clear evidence for toy boy proclivities in females or males was found. Future studies utilizing the methodology used in this study to examine other human mating decision making processes are proposed.     

Paternal age and Down's syndrome genotypes diagnosed prenatally: No association in New York State data

Summary An investigation of a paternal age effect independent of maternal age was undertaken for 98 cases of Down's syndrome genotypes diagnosed prenatally compared to 10,329 fetuses with normal genotype diagnosed prenatally in data reported to the New York State Chromosome Registry. The mean of the difference (delta) in paternal age of cases compared to those with normal genotypes after controlling for maternal age, was slightly negative,-0.27 with a 95% confidence interval of-1.59 to +1.06. A regression analysis was also done in which the data were first fit to an equation of the type lny=(bx+c) and then to the equation ln y=(bx+dz+c) where y = rate of Down's syndrome, x = maternal age, z = paternal age, and b, d, and c are parameters. This also revealed no evidence for a paternal age effect. The value of d (the paternal age coefficient) was in fact slightly negative,-0.0058, with an asymptotic 95% confidence interval of-0.0379 to +0.0263. Lastly, multiple applications of the Mantel-Haenszel test considering various boundaries in paternal age also revealed no statistically significant evidence for a paternal age effect independent of maternal age. These results are at variance with claims of others elsewhere of a very strong paternal age effect detected in studies at prenatal diagnoses. Five different hypotheses are suggested which may account for discrepancies among studies to date in findings on paternal age effects for Down's syndrome: (i) there are temporal, geographic, or ethnic variations in paternal age effects, (ii) there is no paternal age effect and statistical fluctuation accounts for all trends to date; (iii) methologic artifacts have obscured a paternal age effect in some studies which did not find a positive outcome; (iv) methodologic artifacts are responsible for the positive results in some studies to date; (v) there is a rather weak paternal age effect independent of maternal age in most if not all populations, but because of statistical fluctuation the results are significant only in some data sets. The results of all data sets to date which we have been able to analyze by one year intervals are consistent with a mean delta of +0.04 to +0.48 and in the value of d (the paternal age coefficient) of +0.006 to +0.017, and it appears the fifth hypothesis cannot be excluded. Projections based on this assumption are presented.     

Malnutrition, menarche, and marriage in rural Bangladesh

In order to assess the impact of nutritional status on the onset of menarche and the association between age at menarche and age at marriage, a survey of 1155 girls, ages 10 through 20, was conducted in a rural area of Bangladesh in March 1976. In order to obtain an estimated mean of age of menarche, probit analysis was used. The mean age of menarche using this technique is estimated at 15.65 for Muslims and 15.91 for Hindus. It was learned that in recent years the age of menarche has increased in a rural area. This increase seems to be associated with malnutrition caused by the war, postwar inflation, floods and famines during the 1971-75 period. When age is controlled for, the prominent effect of weight on menstrual status is evident. 98% of the girls whose weights were 88 pounds or greater had reached menarche compared to only 1% of those weighing less than 66 pounds. Body weight appears to be 1 of the most important factors for the determination of onset of menarche. There exists a seasonality of onset of menarche with a peak in winter. Age of marriage among this rural population has increased and may be associated with the increasing age of menarche. Since both age of menarche and age of marriage have increased, fertility among females age 15-19 may be expected to decrease in the future if this pattern continues.