The hunger strikes back: an epigenetic memory for autophagy

Abstract

Historical and demographical human cohorts of populations exposed to famine, as well as animal studies, revealed that exposure to food deprivation is associated to lasting health-related effects for the exposed individuals, as well as transgenerational effects in their offspring that affect their diseases’ risk and overall longevity. Autophagy, an evolutionary conserved catabolic process, serves as cellular response to cope with nutrient starvation, allowing the mobilization of an internal source of stored nutrients and the production of energy. We review the evidence obtained in multiple model organisms that support the idea that autophagy induction, including through dietary regimes based on reduced food intake, is in fact associated to improved health span and extended lifespan. Thereafter, we expose autophagy-induced chromatin remodeling, such as DNA methylation and histone posttranslational modifications that are known heritable epigenetic marks, as a plausible mechanism for transgenerational epigenetic inheritance of hunger.

The Metabolic Syndrome, a Human Disease

“…The epidemiology of MS shows that, in a few generations, a society may often pass from a survival stage, under the permanent danger of famine, (nutrition transition) to high food availability [952] and gluttony-overeating [953], helping to induce a massive development of obesity [954,955]. Probably, the sociobiological roots of these (social evolution) sudden shifts may lie in 'epigenetic hunger': memories and functional/behavioral patterns acquired from prenatal experiences or transmitted from previous generations [956,957]. The relative coincidence of increases in MS expansion in countries that have recently endured harsh stress and starvation conditions hints at learned overeating as a precaution [953], but also at overfeeding of children, as is the common situation of proudly showing-off chubby babies (linked to a positive view of children obesity) [958].…”

“…hunger': memories and functional/behavioral patterns acquired from prenatal experiences or transmitted from previous generations [956,957]. The relative coincidence of increases in MS expansion in countries that have recently endured harsh stress and starvation conditions hints at learned overeating as a precaution [953], but also at overfeeding of children, as is the common situation of proudly showing-off chubby babies (linked to a positive view of children obesity) [958].…”

Longevity extension in rats via improved redox homeostasis with high carbohydrate diet intervention from weaning to adulthood: a comprehensive multi-omics study

“…13 Current research suggests that dietary energy restriction, rhythmic eating, and fasting are recognized dietary structures that can improve health and extend lifespans. 2,14,15 However, the restrictive conditions present in these dietary structures are difficult to meet in daily life. 16,17 Energy restriction and regular eating times are even more challenging to sustain in adolescents with high growth and developmental needs and low self-control.…”