Early-life Diet Research Articles

Lasting effects on body weight and mammary gland gene expression in female mice upon early life exposure to n-3 but not n-6 high-fat diets.

Exposure to an imbalance of nutrients prior to conception and during critical developmental periods can have lasting consequences on physiological processes resulting in chronic diseases later in life. Developmental programming has been shown to involve structural and functional changes in important tissues. The aim of the present study was to investigate whether early life diet has a programming effect on the mammary gland. Wild-type mice were exposed from 2 weeks prior to conception to 6 weeks of age to a regular low-fat diet, or to high-fat diets based on either corn oil or flaxseed oil. At 6 weeks of age, all mice were shifted to the regular low-fat diet until termination at 10 weeks of age. Early life exposure to a high-fat diet, either high in n-6 (corn oil) or in n-3 (flaxseed oil) polyunsaturated fatty acids, did not affect birth weight, but resulted in an increased body weight at 10 weeks of age. Transcriptome analyses of the fourth abdominal mammary gland revealed differentially expressed genes between the different treatment groups. Exposure to high-fat diet based on flaxseed oil, but not on corn oil, resulted in regulation of pathways involved in energy metabolism, immune response and inflammation. Our findings suggest that diet during early life indeed has a lasting effect on the mammary gland and significantly influences postnatal body weight gain, metabolic status, and signaling networks in the mammary gland of female offspring.

Neuroimaging, a new tool for investigating the effects of early diet on cognitive and brain development.

Nutrition is crucial to the initial development of the central nervous system (CNS), and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of “programming” where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism's structure or function. Nutrition was first shown to be a programming stimulus for growth, and then for cognitive behavior, in animal studies that were able to employ methods that allowed the demonstration of neural effects of early nutrition. Such research raised the question of whether nutrition could also programme cognition/brain structure in humans. Initial studies of cognitive effects were observational, usually conducted in developing countries where the presence of confounding factors made it difficult to interpret the role of nutrition in the cognitive deficits that were seen. Attributing causality to nutrition required randomized controlled trials (RCTs) and these, often in developed countries, started to appear around 30 years ago. Most demonstrated convincingly that early nutrition could affect subsequent cognition. Until the advent of neuroimaging techniques that allowed in vivo examination of the brain, however, we could determine very little about the neural effects of early diet in humans. The combination of well-designed trials with neuroimaging tools means that we are now able to pose and answer questions that would have seemed impossible only recently. This review discusses various neuroimaging methods that are suitable for use in nutrition studies, while pointing out some of the limitations that they may have. The existing literature is small, but examples of studies that have used these methods are presented. Finally, some considerations that have arisen from previous studies, as well as suggestions for future research, are discussed.

Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50% of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate-high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORMHCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P<0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P<0·05), increased neonatal appetite for fat-(P=0·004) rather than carbohydrate-rich feeds (P<0·001) and reduced deposition of subcutaneous fat in both sexes (P<0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P<0·001). Postnatal overfeeding (HCHF) resulted in obesity (.30% fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.

Diet, residential origin, and pathology at Machu Picchu, Peru

Pathological conditions in human skeletal remains provide a wealth of information about archaeological populations, but many are limited in their interpretive significance by their nonspecific etiologies. This study analyzes three common pathological conditions known to manifest in infancy and childhood in the skeletal population from Machu Picchu, Peru (N = 74) with published carbon, nitrogen, oxygen, strontium, and lead isotopic data (Turner et al.: J Archaeol Sci 36 (2009) 317-332; Turner et al.: Chungara: Revista de Antropología Chilena 42 (2010) 515-524) to distinguish early-life diet from residential origins as significantly associated with pathologies among the site's inhabitants. Analyses of variance indicate highly significant variation between enamel δ(18)O values, which serve as a rough proxy of local environment, and both cribra orbitalia (CO) and porotic hyperostosis (PH), generally understood to be markers of anemia. Results tentatively suggest that individuals manifesting these lesions may have lived closer to the arid coasts; however, no significant variation was found in parameters of diet (enamel δ(13) C(carbonate), dentin δ(13) C(collagen), dentin δ(15)N) by either CO or PH, suggesting that the primary factors causing anemia may have been more significantly related to residential origin rather than diet. Linear enamel hypoplasia (LEH) frequency significantly varied by both dietary and residential parameters, supporting models of LEH formation from a synergy of dietary and environmental factors. These results support previous research on the etiology of PH in the Andes; they also represent a useful approach to refining site-specific interpretations of pathological conditions in archaeological populations, and exploring etiological variation between populations.

Arachidonic acid/docosahexaenoic acid‐supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3Leiden mice

This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and mild obesity. Four-week-old male ApoE*3Leiden mice were fed chow diet with or without a mixture of ARA (0.129 wt%) and DHA (0.088 wt%) or Omacor (0.30 wt% EPA, 0.25 wt% DHA). At age 12 weeks, mice were fed high-fat/high-carbohydrate (HFHC) diet without above supplements until age 20 weeks. Control mice received chow diet throughout the study. Mice receiving ARA/DHA gained less body weight compared to control and this effect was sustained when fed HFHC. Omacor had no significant effect on body weight gain. Plasma cholesterol and triglycerides were significantly lowered by both supplementations. At 20 weeks, epididymal fat mass was less in ARA/DHA-supplemented mice, while Omacor had no significant effect on fat mass. Both ARA/DHA and Omacor reduced inguinal adipocyte cell size; only ARA/DHA significantly reduced epididymal macrophage infiltration. This study shows that early life ARA/DHA, but not Omacor supplementation improves body weight gain later in life. ARA/DHA and to a lesser extent Omacor both improved adipose tissue quality.

Histone deacetylase 3 (HDAC3) participates in the transcriptional repression of the p16INK4a gene in mammary gland of the female rat offspring exposed to an early-life high-fat diet

Maternal exposure to environmental agents throughout pregnancy and lactation may affect offspring’s mammary gland growth and alter the epigenome. This may predispose the offspring’s mammary glands to be more susceptible to carcinogenesis. The purpose of this study was to examine the effect of a maternal high-fat diet on the regulation of p16INK4a gene expression in the mammary gland of rat offspring. Timed-pregnant Sprague-Dawley rats were fed one of the two diets, a control (C, 16% of fat) or a high fat (HF, 45% of fat) diet, throughout gestation and lactation and sacrificed at 12 weeks of age. Compared with C, HF offspring showed a decrease of p16INK4a gene expression in the mammary gland at both mRNA and protein levels. Chromatin immunoprecipitation (ChIP) assay demonstrated that the downregulation of p16INK4a transcription in HF offspring was associated with reduced acetylation of histone H4 and increased recruitment of histone deacetylase 3 (HDAC3) within the p16INK4a promoter region, but was not associated with acetylation of histone H3 or HDAC1. Methylated DNA immunoprecipitation (MeDIP) did not detect differences in methylation at different regions of the p16INK4a gene between C and HF offspring. We conclude that maternal high fat exposure represses p16INK4a gene expression in the mammary gland of offspring through changes of histone modifications and HDAC3 binding activity within the regulatory regions of the p16INK4a gene.

Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet

In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.

IGF-I and IGFBP-3 in healthy 9 month old infants from the SKOT cohort: Breastfeeding, diet, and later obesity

BackgroundHigh IGF-I concentrations in infancy have been associated with later obesity but the interactions between diet, IGF-I concentrations and growth in early life are complex and involve programming of the IGF-I axis. ObjectiveThis paper examines how IGF-I and IGFBP-3 concentrations measured at age 9months are related to diet and growth in infancy. DesignIn the Danish SKOT cohort healthy term infants were included at age 9months with follow-up at age 18months. Total 252 infants had a full data set and were included in the analysis. Measurements include weight, length, skinfold thickness, waist circumference, 7-d food records, and blood analysis of IGF-I, and IGFBP-3. ResultsInfants not being breastfed at 9months of age (46%) had higher median IGF-I concentration than breastfed infants (51.6 vs. 44.2ng/mL, P=0.0005) and there was a negative dose response effect of daily numbers of breastfeedings on IGF-I concentration. IGF-I concentration was negatively associated with birth weight and positively related to increase in weight, length and BMI between birth and 9months. Between 9months and 18months of age increase in length was positively and increase in BMI was negatively related to IGF-I concentration. ConclusionBreastfeeding has a strong negative effect on IGF-I concentrations in late infancy. Although IGF-I concentrations at 9months of age were negatively associated with change in BMI during the following 9months we speculate that this could reflect an early adiposity rebound and thereby an increased risk of obesity later in life.

Maternal Nutrient Restriction During Late Gestation and Early Postnatal Growth in Sheep Differentially Reset the Control of Energy Metabolism in the Gastric Mucosa

Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.

Thrifty development: early-life diet restriction reduces oxidative damage during later growth

1. Conditions during early stages of life may have an important effect on phenotype, by inducing programmed responses that may remain throughout the lifetime of an animal. One very important factor that can promote long-term changes in phenotype is restriction of food intake (dietary restriction, DR). 2. Recently, it has been shown that DR may induce an increase in antioxidant and repair mechanisms as a result of hormetic responses. Interestingly, the induction of antioxidant and repair mechanisms may be triggered by transitory increases in reactive oxygen species. Dietary-derived antioxidants, such as vitamin E, may be important to determine the compensatory effect of DR. 3. To investigate the effect of DR on attenuation of oxidative damage, we manipulated dietary intake (by restricting food ingestion) and antioxidant availability (by vitamin E supplementation) during the first days of life of yellow-legged gull (Larus michahellis) chicks. We then measured oxidative status and body mass during the early development of chicks. 4. We found that an early short event of food shortage strongly affected the oxidative status of the chicks and their growth patterns. We observed less oxidative damage to proteins and DNA in dietary restricted chicks, after the period of food restriction, than in non-restricted chicks. Unexpectedly, vitamin E supplementation did not suppress the hormetic effect of DR, but instead increased it. 5. These novel results support the idea that short events of DR during early development induce a reduction in oxidative damage in wild animals. The results suggest that DR promotes the induction of an early hormetic response in some antioxidant defence processes and/or repair mechanisms. These findings have important implications for our understanding of how early conditions may shape the phenotype of an organism, and also for the study of evolutionary trade-offs during early growth.

Breastfeeding, IGF‐I, adiposity rebound and childhood obesity in the Danish SKOT cohort

High IGF-I concentrations in infancy has been associated with later obesity but the interactions between diet, IGF-I and growth in early life are complex as it also include early programming of the IGF-I axis. The objective was to examine diet, IGF-I, and growth in a cohort of healthy term infants in the Danish SKOT cohort. 252 infants were included at age 9 mo and followed up at age 18 mo. Plasma IGF-I was measured at 9 mo and anthropometry at 9 and 18 mo. Infants not being breastfed at 9 mo of age (46%) had higher median IGF-I concentration than breastfed infants (51.6 vs. 44.2 ng/mL) and there was a strong negative dose response effect of daily number of breastfeeding's on IGF-I concentration. IGF-I was negatively associated with birth weight and positively with increase in weight, length and BMI between birth and 9 mo. Between 9 and 18 mo IGF-I was positively related to increase in length, but negatively to change in BMI. Although infants with high IGF-I at 9 mo thus became thinner during the following 9 mo we speculate that this could reflect an early adiposity rebound and thereby an increased risk of obesity later in life.

Exposure of the Pregnant Rat to Low Protein Diet Causes Impaired Glucose Homeostasis in the Young Adult Offspring by Different Mechanisms in Males and Females

The understanding of the mechanisms by which gender dimorphisms are involved in the modulation of insulin sensitivity and glucose tolerance can be crucial to unravel the development of type 2 diabetes. Rats treated with a low protein diet (LP, 8% protein content) during pregnancy and lactation have a reduced beta-cell mass at birth and a reduced insulin secretion at weaning. In this study we examined the effect of LP diet on glucose homeostasis from birth to adulthood when offspring previously exposed to LP were subsequently switched to control diet (C, 20% protein content) at weaning. The LP group had a reduced body weight after weaning compared to the C-fed rats, although their food intake was not significantly different. Furthermore, LP males had a significant increase in visceral adiposity relative to their body weight (P < 0.05). Intraperitoneal glucose tolerance test (IGTT) showed that glucose clearance was unchanged until 130 days of age when LP-fed females showed elevated blood glucose compared to C, despite similar plasma insulin levels. Females also demonstrated a significant reduction in mean pancreatic islet number, individual islet size and beta cell mass. However, no differences in IGTT or islet morphometry were observed in LP males, although basal insulin levels were twofold higher. Akt phosphorylation in response to insulin was reduced in adipose and skeletal muscle of adult rats following exposure to LP diet in early life when compared to control-fed animals, but this was only apparent in males. Plasma testosterone levels were also reduced in males at 130 days age. These data suggest that the development of impaired glucose homeostasis in offspring of LP-fed rats is likely to occur by different mechanisms in males and females.

Effect of the early-life nutritional environment on fecundity and fertility of mammals

The early-life developmental environment is instrumental in shaping our overall adult health and well-being. Early-life diet and endocrine exposure may independently, or in concert with our genetic constitution, induce a pathophysiological process that amplifies with age and leads to premature morbidity and mortality. Recently, this has become known as ‘programming’ but is akin to ‘maternal effects’ described for many years in the biological sciences and is defined as any influence that acts during critical developmental windows to induce long-term changes in the organisms' phenotype. To date, such delayed maternal effects have largely been characterized in terms of susceptibility to cardiovascular or metabolic disease. Here, we review evidence from experimental animal species, non-human primates and man for an effect of the early-life nutritional environment on adult fecundity and fertility. In addition, using a database of pedigree sheep, we also specifically test the hypothesis that being born small for gestational age with or without post-natal growth acceleration directly programmes fertility. We conclude that there is a lack of compelling evidence to suggest pre-natal undernutrition may directly reduce adult fecundity and fertility, but may exert some effects secondarily via an increased incidence of ‘metabolic syndrome’. Possible effects of being born relatively large on subsequent fecundity and fertility warrant further investigation.

A low protein diet in early life delays the onset of diabetes in the non-obese diabetic mouse

Dietary insult in early life can affect the development and future function of the endocrine pancreas. We maintained pregnant non-obese diabetic (NOD) mice on a low protein (LP, 8% protein versus control, 20%) diet from conception until the weaning of pups at day 21. Serum insulin and pancreatic insulin content were reduced in LP-fed NOD offspring at 8 weeks, as were serum interferon gamma and pancreatic tumor necrosis factor alpha, while the number of pancreatic islets demonstrating peri-insulitis, and the degree of invasiveness were reduced. To determine if LP caused early morphometric changes in the pancreas, we measured mean islet area at days 3 and 21. Mean islet size did not differ with diet, but by 8 weeks of age LP-fed NOD females exhibited a significantly reduced islet number and mean islet area, and a lower fractional area of pancreas occupied by both alpha- and beta-cells than control-fed mice. The onset of diabetes was delayed in NOD mice of both genders fed LP diet. The mechanism is likely to involve both altered beta-cell morphology and function and changes in cytotoxic cytokines.

Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming – long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research

Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.

Early life events in asthma—diet

It has been hypothesized that the recent increase in the prevalence of asthma may, in part, be a consequence of changing diet. There is now increasing interest in the possibility that childhood asthma may be influenced by maternal diet during pregnancy and/or diet during early childhood. A number of observational studies and a childhood fish oil supplementation study provide little support for the notion that early childhood intake of polyunsaturated fatty acids (PUFAs) influence the development of childhood asthma. Recent work however, suggests that supplementation of maternal diet with fish oil is associated with altered neonatal immune responses to allergens. Further work is required to establish whether this immunological observation is translated into clinical outcomes. Two birth cohorts have now reported reduced maternal intake of vitamin E, zinc and vitamin D during pregnancy to be associated with increased asthma and wheezing outcomes in children up to the age of 5 years. Early life diet could modulate the likelihood of childhood asthma by affecting fetal airway development and/or influencing the initial early life interactions between allergens and the immune system. In animal models, vitamin E, zinc and vitamin D have been shown to modify fetal lung development and vitamin E, zinc, vitamin D and PUFA can modulate T-cell responses. Further research, particularly, early life intervention studies need to be carried out to establish whether early life dietary intervention can be used as a public health measure to reduce the prevalence of childhood asthma.

Early life diet enrichment with arachidonic and docosahexaenoic acids attenuates the effects of intrauterine growth restriction on bone mass in weanling guinea pigs

Early life diet enrichment with arachidonic and docosahexaenoic acids attenuates the effects of intrauterine growth restriction on bone mass in weanling guinea pigs

Early Life Diet and the Risk for Adult Breast Cancer

: A hypothesis postulating intrauterine and early life influences on the occurrence of breast cancer in adult life has received considerable support in the literature. We present alternative or complementary ways through which diet could affect breast cancer risk in this context. Emphasis is placed on evidence that reduced energy intake in early life is associated with smaller body size, which, in turn, constrains birth weight and subsequent development of offspring and is associated with reduced breast cancer risk.

Adult sterol metabolism is not affected by a positive sterol balance in the neonatal Golden Syrian hamster

Dietary components impact metabolism early in life. Some of the diet-induced effects are long lasting and can lead to various adult-based diseases. In the current studies, we examined the short-term effects of dietary cholesterol on neonatal hepatic sterol metabolism and the long-term effects that those early-life diets had on sterol metabolism in adulthood. Neonatal hamsters began consuming solid food as a supplement to milk by 5 days of age; diets contained 0 or 2% added cholesterol (wt/wt). By 10 days of age, plasma and liver cholesterol concentrations were 3.2- and 2.5-fold greater, respectively, in the neonates fed cholesterol. Hepatic sterol synthesis rates were suppressed 65% in cholesterol-fed neonates compared with control neonates. By 20 days of age, plasma and liver cholesterol concentrations were still greater and sterol synthesis rates were now suppressed maximally in neonates fed cholesterol compared with control neonates. The expression level of an apolipoprotein B-containing lipoprotein receptor (low-density lipoprotein receptor-related protein) was greater and the mature form of the sterol regulatory element-binding protein-2 was similar in livers of 20-day-old control neonates compared with control neonates at 10 days of age. To test whether the change in sterol balance in the neonatal period had a lasting effect on hepatic sterol metabolism, all animals were weaned on a low-cholesterol diet. At 70 days of age, hepatic sterol synthesis rates, plasma lipoprotein and liver cholesterol concentrations, and bile acid pool sizes and compositions were measured. Sterol balance in the adults was similar between animals fed either diet early in life, as demonstrated by a lack of difference in any parameter measured. Thus, even though dietary cholesterol suppressed hepatic sterol synthesis rates dramatically in the neonatal hamster, the change has little impact on sterol balance later in life.

The Cohort Effect: Insights and Explanations

ABSTRACTThe purpose of the report is to achieve a greater understanding of the United Kingdom ‘cohort effect’ by exploring research in other fields and analysing population mortality data by cause of death in more detail. The ‘cohort effect’ in this context is the observed phenomenon that people born in the U.K. between 1925 and 1945 (centred on the generation born in 1931) have experienced more rapid improvement in mortality than generations born either side of this period.In a Continuous Mortality Investigation (CMI) Bureau working paper published in 2002, a similar trend was noted in the mortality experience of male pensioners and males with life assurance policies. The CMI Bureau investigation showed peak rates of improvement for the cohort born in 1926. Interim projection bases for future mortality experience were produced as a result of the study. The projections made various assumptions about the extent to which the observed cohort effect would continue to shape the pattern of future mortality improvement.This report suggests that it is highly likely that the cohort effect has been caused by a number of different factors in combination. Prevalence of smoking from one generation to the next has certainly been one such factor. Furthermore, an analysis of patterns of cigarette smoking suggests that there is a degree of inevitability in some element of likely future improvement, especially for mortality at older ages from conditions strongly linked to smoking.However, trends in heart disease and breast cancer mortality suggest that smoking is not the only factor. The differences between lung cancer and heart disease trends by year of birth are especially interesting. The report shows that there are two ‘sub-cohorts’ of the 1925 to 1945 cohort: an earlier group where the improvements may be largely due to smoking; and a later one where other factors, such as diet in early life, may have played a greater role.Historic patterns of smoking behaviour by socio-economic class provide an explanation for the five-year difference in the year of birth showing the fastest improvements, i.e. the difference between 1926 for the CMI Bureau investigation and 1931 for the general population. It is also notable that the second ‘sub-cohort’ of high improvement, applying to people born in the early 1940s, can be seen in both population and CMI experience.A case study examining Japanese mortality experience shows that strong cohort trends can be projected well into old age. This does not provide proof that the U.K. cohort effect will do the same. However, it does counter arguments that year of birth effects will inevitably wear off with age. It is especially interesting given recent epidemiological research linking early life experience with markers of ageing.There are a number of reasons to believe that the U.K. cohort effect will have an enduring impact on rates of mortality improvement in future decades. These include historical patterns of smoking behaviour and the impact of early life experience on health in later life. There appears to be little evidence to support the idea that the width of the generation experiencing rapid improvement will reduce with time.