Epigenetic inheritance of proteostasis and ageing

Abstract

Abundant evidence shows that the genome is not as static as once thought and that gene expression can be reversibly modulated by the environment. In some cases, these changes can be transmitted to the next generation even if the environment has reverted. Such transgenerational epigenetic inheritance requires that information be stored in the germline in response to exogenous stressors. One of the most elusive questions in the field of epigenetic inheritance is the identity of such inherited factor(s). Answering this question would allow us to understand how the environment can shape human populations for multiple generations and may help to explain the rapid rise in obesity and neurodegenerative diseases in modern society. It will also provide clues on how we might be able to reprogramme the epigenome to prevent transmission of detrimental phenotypes and identify individuals who might be at increased risk of disease. In this article, we aim to review recent developments in this field, focusing on research conducted mostly in the nematode Caenorhabditis elegans and mice, that link environmental modulators with the transgenerational inheritance of phenotypes that affect protein-folding homoeostasis and ageing.

Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species

“…In evolutionary terms, the transmission of the adaptive transcriptional patterns acquired throughout the parental life course in subsequent generations via the mechanism of epigenetic memory can enable the organism to better survive in potentially adverse environments [ 84 ]. In particular, it has been repeatedly reported that offspring of parents exposed to nutritional stresses exhibit altered expression of genes related to metabolic functions including those implicated in pro-longevity metabolic pathways [ 6 ]. The mechanisms potentially responsible for such inter- and transgenerational effects are currently the subject of active investigation [ 5 , 14 , 85 – 89 ].…”

“…It should be taken into consideration that when discussing such effects in any species that the first generation’s primordial germ cells can be affected by in utero exposure. Thus, we must distinguish between parental effects triggered by certain environmental cues in the developing fetus, including the germline (i.e., intergenerational effects), from truly transgenerational effects induced in subsequent generations that were not exposed to the initial environmental triggers [ 6 ]. Most literature on transgenerational effects is focused mainly on maternal contribution to offspring phenotypes, while paternal effects are considered quite rare.…”

“…In several recent studies, the potential importance of non-genomic transgenerational effects in the inheritance of age-related characteristics has been highlighted [ 6 ]. In particular, the evidence for transgenerational effects of maternal diet on reproductive and metabolic aging in offspring has been obtained in various mammalian species such as guinea pigs, rodents, and sheep [ 17 ]; however, the transgenerational effects on longevity have been reported only rarely to date.…”

Empirical Validation of a Hypothesis of the Hormetic Selective Forces Driving the Evolution of Longevity Regulation Mechanisms

“…Indeed, recent evidence indicates that various environmental, dietary, genetic, and pharmacological interventions elicit certain epigenetic changes that can influence the aging process and define longevity in evolutionarily distant eukaryotic organisms (Dang et al, 2009; Greer et al, 2010; Li et al, 2011; Moskalev et al, 2014; Benayoun et al, 2015; Li and Casanueva, 2016; Pal and Tyler, 2016; Sen et al, 2016). Some of these epigenetic changes can be epigenetically inherited for several generations, thus they can act in a transgenerational manner to affect the rate of aging and define the lifespan of the offspring (Greer et al, 2011; Benayoun et al, 2015; Li and Casanueva, 2016; Pal and Tyler, 2016). …”

Epigenetics of Subcellular Structure Functioning in the Origin of Risk or Resilience to Comorbidity of Neuropsychiatric and Cardiometabolic Disorders

“…Epigenetic markers and their inheritance can contribute to proteostasis-related phenotypes determined by the response to stress of the ER across generations [ 26 ]. The epigenetic markers on ER stress might contribute to metabolic diseases.…”