Epigenetic responses to heat: From adaptation to maladaptation

Abstract

New Findings What is the topic of this review?This review outlines the history of research on epigenetic adaptations to heat exposure. The perspective taken is that adaptations reflect properties of hormesis, whereby low, repeated doses of heat induce adaptation (acclimation/acclimatization); whereas brief, life‐threatening exposures can induce maladaptive responses. What advances does it highlight?The epigenetic mechanisms underlying acclimation/acclimatization comprise specific molecular programmes on histones that regulate heat shock proteins transcriptionally and protect the organism from subsequent heat exposures, even after long delays. The epigenetic signalling underlying maladaptive responses might rely, in part, on extensive changes in DNA methylation that are sustained over time and might contribute to later health challenges. Abstract Epigenetics plays a strong role in molecular adaptations to heat by producing a molecular memory of past environmental exposures. Moderate heat, over long periods of time, induces an ‘adaptive’ epigenetic memory, resulting in a condition of ‘resilience’ to future heat exposures or cross‐tolerance to other forms of toxic stress. In contrast, intense, life‐threatening heat exposures, such as severe heat stroke, can result in a ‘maladaptive’ epigenetic memory that can place an organism at risk of later health complications. These cellular memories are coded by post‐translational modifications of histones on the nucleosomes and/or by changes in DNA methylation. They operate by inducing changes in the level of gene transcription and therefore phenotype. The adaptive response to heat acclimation functions, in part, by facilitating transcription of essential heat shock proteins and exhibits a biphasic short programme (maintaining DNA integrity, followed by a long‐term consolidation). The latter accelerates acclimation responses after de‐acclimation. Although less studied, the maladaptive responses to heat stroke appear to be coded in long‐lasting changes in DNA methylation near the promoter region of genes involved with basic cell function. Whether these memories are also encoded in histone modifications is not yet known. There is considerable evidence that both adaptive and maladaptive epigenetic responses to heat can be inherited, although most evidence comes from lower organisms. Future challenges include understanding the signalling mechanisms responsible and discovering new ways to promote adaptive responses while suppressing maladaptive responses to heat, as all life forms adapt to life on a warming planet.

Impact of passive heat stress and passive heat acclimation on circulating extracellular vesicles: An exploratory analysis

“…Regardless of the potential functional significance of an increase in total and platelet EVs during heat stress, a new observation of the present analysis is that heat acclimation does not minimize this increase. Animal models have shown that heat adaptation upregulates cytoprotective pathways that lead to greater cellular resilience to various stressors (Murray et al., 2022 ). The cellular adaptations of human heat adaptation are less understood, although several studies have considered elements of the heat shock response (Amorim et al., 2015 ; Hoekstra et al., 2020 ).…”

“…The cellular responses to heat stress progress along a continuum, from improved cellular thermotolerance following repeated moderate heat exposure to cellular apoptosis during severe heat strain. These cellular outcomes are mediated by intra‐ and extracellular signals, including alarmins, endotoxins, microRNAs and chromatin modifiers (Bouchama et al., 2022 ; Horowitz, 2014 ; Murray et al., 2022 ). Accumulating, albeit still limited, evidence suggests that extracellular vesicles (EVs) might also contribute to cellular signalling and therefore the cellular adaptations in response to heat stress (Bain et al., 2017 ; Bouchama et al., 2008 ; Coombs et al., 2019 ; Wilhelm et al., 2017 ).…”

Exertional Heat Stroke and Rhabdomyolysis: A Medical Record Review and Patient Perspective on Management and Long-Term Symptoms

“…However, we found that ambient temperatures on the day of the event were higher than what is typically expected [ 31 ]. The role of heat acclimatization in the pathophysiology of EHS has been investigated, and studies have noted epigenetic adaptations facilitating the regulation of heat shock proteins that protect individuals from heat illness after exposure to heat [ 47 – 49 ]. In most individuals, adaptations to heat exposure develop during the first 4 days and are completed within 3 weeks [ 50 ].…”

Thyroid hormone links environmental signals to DNA methylation

“…For example, unusually warm winters cause a mismatch between seasonal light cycles and temperature cycles that impacted thyroid hormone signalling in mosquitofish ( Gambusia holbrooki ) [91] and caused physiological dysfunction in mice [92]. Similarly, heatwaves can have a broad range of epigenetic effects [93] and caused changes to methylation patterns in a polychaete ( Spiophanes tcherniai ) [85] that can potentially be passed across generations [94].…”