The developmental origins of ageing: study protocol for the Dutch famine birth cohort study on ageing

Abstract

IntroductionEvidence from animal studies suggest that the rate of ageing may be influenced not only by genetic and lifestyle factors, but also by the prenatal environment. We have previously shown that people who were exposed to famine during early gestation performed worse on a selective attention task, which may be a first sign of cognitive decline, and were on average 3 years younger at the time of coronary artery disease diagnosis. Women in this group seem to die at a younger age. We hypothesise that an accelerated ageing process, set in motion by the poor prenatal environment, underlies these findings.Methods and analysisThe Dutch Famine Birth Cohort consists of 2414 men and women born in Amsterdam as term singletons around the time of the Dutch famine. In a subsample of 150 cohort members, who now are about 68 years of age, we are currently measuring cognitive decline and the incidence of white matter hyperintensities and cerebral microbleeds (through MRI), incidence of fractures, grip strength and physical performance, visual acuity and incidence of cataract operations. In this same subgroup, we will assess telomere length, oxidative stress and inflammatory status as potential underlying mechanisms. Furthermore, in the entire cohort, we will assess mortality as well as hospital admissions for age-related diseases up to the age of 68 years.Ethics and disseminationThe study was approved by the local medical ethics committee (Academic Medical Centre, University of Amsterdam) and is being carried out in agreement with the Declaration of Helsinki. All participants give written informed consent. Study findings will be widely disseminated to the scientific public as well as to the medical society and general public.

Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise

“…In the same study, at the organ/system level, the authors demonstrated larger increases in levels of aging biomarkers in the brain, bone, skeletal muscle and the eye. At the cellular level, increased inflammation, oxidative stress and decreased telomere length of DNA, a hallmark of cellular senescence, were evident (de Rooij & Roseboom, ). Overall, this evidence has led to the emergence of the notion that, even decades later, organs, tissues and even cells can be programmed as a result of early‐life foetal environmental encounters.…”

Differences between biological and chronological age‐at‐death in human skeletal remains: A change of perspective

“…Taking the opposite view, this research maintains that ‘inaccuracy’, i.e., the difference between CA and BA, is a repercussion of individual variations in longevity as well as individual differences in the onset and variations in the aging processes due to genetic, epigenetic, and environmental conditions (Bae et al, ; Belsky et al, ; Cho, Park, & Lim, ; de Rooij & Roseboom, ; Levine, ). Indeed, research in living populations found the estimated standard deviation of the difference between CA and BA varies between three and 10 years (Belsky et al, ; Hochschild, ; Klemera & Doubal, ), and because the health of individuals is highly heterogeneous, as is the rate of aging, discordances between BA and CA can take place from a young age (Belsky et al, ; Molinari, Gasser, & Largo, ; Wiweko et al, ) not just among older individuals as is often assumed.…”

“…When genes appear to be altered in expression, it is not “age” per se to which they are responding but “state,” e.g., an accumulation of DNA damage (Kirkwood & Melov, ). Hence, the discordance between CA and BA is due to the individual continuous interaction between physiological, morphological, and social spheres—together with lifestyle and living conditions—experienced by an individual since early fetal development (de Rooij & Roseboom, ; Mitnitski et al, ). Thus, the synchronicity between CA with growth trajectories, body composition, and development, from the early stages of life can be interrupted by a stochastic dynamic of environmental (intrinsic and extrinsic), genetic, and epigenetic factors (Bline, Dylewski, Driscoll, & Fuzaylov, ; Lei, Simons, Beach, & Philibert, ; Liston & Rotroff, ; Mitnitski et al, ; Richmond & Rogol, ).…”

Epigenetic inheritance of proteostasis and ageing

“…This accelerated ageing and loss of fertility may be linked to increased oxidative stress [ 51 , 54 ], which is known to contribute to ageing. New studies are planned to address the possibility of an accelerated ageing phenotype in humans in response to maternal nutrition [ 55 ]. Most of the aforementioned studies have addressed inter-generational memory of phenotypes and very few studies have assessed whether environmentally induced transgenerational inheritance of phenotypes persists beyond F2.…”