The impact of early nutrition on the ageing trajectory

Abstract

Epidemiological studies, including those in identical twins, and in individuals in utero during periods of famine have provided robust evidence of strong correlations between low birthweight and subsequent risk of disease in later life, including type 2 diabetes (T2D), CVD, and metabolic syndrome. These and studies in animal models have suggested that the early environment, especially early nutrition, plays an important role in mediating these associations. The concept of early life programming is therefore widely accepted; however the molecular mechanisms by which early environmental insults can have long-term effects on a cell and consequently the metabolism of an organism in later life, are relatively unclear. So far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification and microRNA) and permanent changes in cellular ageing. Many of the conditions associated with early-life nutrition are also those which have an age-associated aetiology. Recently, a common molecular mechanism in animal models of developmental programming and epidemiological studies has been development of oxidative stress and macromolecule damage, specifically DNA damage and telomere shortening. These are phenotypes common to accelerated cellular ageing. Thus, this review will encompass epidemiological and animal models of developmental programming with specific emphasis on cellular ageing and how these could lead to potential therapeutic interventions and strategies which could combat the burden of common age-associated disease, such as T2D and CVD.

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

“…These findings have been robustly confirmed in both humans and animals (Tarry-Adkins and Ozanne, 2014; Zambrano et al, 2016), and these studies support the ‘thrifty phenotype hypothesis’ (Hales and Barker, 1992), which states that, under conditions of suboptimal nutrition, the fetus permanently alters its organ structure, metabolism and function to ensure immediate survival of the organism. Although beneficial in continued conditions of poor postnatal nutrition, such ‘developmental programming’ is known to be detrimental in postnatal conditions of adequate or over-nutrition, both of which can cause accelerated postnatal growth.…”

“…This makes telomere length measurement a robust marker of aging in many species, including humans and rodents, and this has been shown to be associated with longevity (Haussman et al, 2003; Heidinger et al, 2012). It is known that suboptimal in utero nutrition can lead to accelerated aging in a number of tissues (Tarry-Adkins and Ozanne, 2014). The high metabolic activity of skeletal muscle renders it particularly susceptible to oxidative stress; however, accelerated aging in skeletal muscle as a consequence of developmental programming has never been explored.…”

The age dependent association between aortic pulse wave velocity and telomere length

“…Our data are in agreement with the majority of published studies showing that shorter TL is associated with increased chronological age (Blasco, 2005). TL is also considered to be significantly affected by genetics, (Brouilette et al 2008;, together with psychosocial and environmental factors such as hostility (Brydon et al 2012), educational attainment , sleep duration (Jackowska et al 2011) and oxidative stress (Kiecolt-Glaser et al 2013;Tarry-Adkins & Ozanne, 2014). Moreover, TL has been linked with both metabolic and CV outcomes in recent meta-analyses (Haycock et al 2014;D'Mello et al 2015), albeit with significant heterogeneity between observations within these studies.…”

Promoting Health and Longevity through Diet: From Model Organisms to Humans

“…For instance, undernourished rat and mouse mothers produce offspring with low birth weight and multiple metabolic defects, including early life adiposity, altered pancreatic function and progressive glucose intolerance (Tarry-Adkins and Ozanne, 2014; Vickers, 2014). Maternal effects on offspring can include changes to the composition of the egg, alterations to the environment in utero , and peri-natal effects such as transmission of the microbiome and alterations to lactation, and can be manifest in the offspring as changes in gene expression and epigenetic modifications including DNA methylation, histone modification and expression of microRNAs, as well as evidence of increased cellular ageing (Aiken and Ozanne, 2014; Colaneri et al, 2013; Radford et al, 2012).…”