Early Adversity and Accelerated Brain Aging: A Mini-Review

Abstract

Early adversity is an important risk factor that influences brain aging. Diverse animal models of early adversity, including gestational stress and postnatal paradigms disrupting dam-pup interactions evoke not only persistent neuroendocrine dysfunction and anxio-depressive behaviors, but also perturb the trajectory of healthy brain aging. The process of brain aging is thought to involve hallmark features such as mitochondrial dysfunction and oxidative stress, evoking impairments in neuronal bioenergetics. Furthermore, brain aging is associated with disrupted proteostasis, progressively defective epigenetic and DNA repair mechanisms, the build-up of neuroinflammatory states, thus cumulatively driving cellular senescence, neuronal and cognitive decline. Early adversity is hypothesized to evoke an “allostatic load” via an influence on several of the key physiological processes that define the trajectory of healthy brain aging. In this review we discuss the evidence that animal models of early adversity impinge on fundamental mechanisms of brain aging, setting up a substratum that can accelerate and compromise the time-line and nature of brain aging, and increase risk for aging-associated neuropathologies.

Oligodendrocytes matter: a review of animal studies on early adversity

“…Considering that growth as well as formation of important neuronal networks and circuitries is linked to myelinization (Tau and Peterson 2010 ; Almeida and Lyons 2017 ), abnormalities in oligodendrocyte maturation or differentiation may play a significant role in the development of cognitive or emotional alterations such as increased anxiety or reduced memory performance. The reported earlier maturation of oligodendrocytes (Teissier et al 2020 ) is in line with accelerated brain maturation as a consequence of early adversity observed in several species (Callaghan and Tottenham 2016 ; Chaudhari et al 2022 ). Earlier maturation of oligodendrocytes along with simpler morphology and reduced differentiation may lead to dysfunction and long-lasting alterations in structural brain development as found in humans after early deprivation in childhood due to institutionalization (Kumsta et al 2017 ; Sheridan et al 2022 ).…”

A method for measuring mitochondrial DNA copy number in pediatric populations

“…There is growing evidence that mitochondrial adaptation as part of the cell danger response (36, 37) may play a central role in various pathophysiological states, including cancer, cardiovascular disease, metabolic disorders and chronic stress (16,19,(38)(39)(40)(41)(42)(43). Mitochondrial DNA copy number is a critical determinant of mitochondrial function, influencing cellular energy production and metabolism (3).…”

Alcohol and stress exposure across the lifespan are key risk factors for Alzheimer's Disease and cognitive decline

“…The disruption of normative adolescent development via stress and/or alcohol use has been implicated in the development of numerous psychiatric disorders ( Brière et al, 2014 ; Fergusson et al, 2013 ; Goodyer et al, 1985 ; Guessoum et al, 2020 ; Pedrelli et al, 2016 ; Rohde et al, 2001 ), and impaired cognitive functioning ( Daughters et al, 2013 ; Ferrett et al, 2010 ; Parada et al, 2012 ; Rahdar and Galván, 2014 ; Sullivan et al, 2016 ). It has been argued that early life adversity, such as adolescent alcohol or stress exposure, may prime the brain for accelerated aging and associated dysfunction ( Chaudhari et al, 2022 ). Few studies have attempted to directly link adolescent alcohol or stress exposure to lifespan cognitive decline due to obvious difficulties in tracking subjects across an entire lifespan, although some have argued for the high likelihood that early life adversity accelerates brain aging and decline ( Chaudhari et al, 2022 ).…”

“…It has been argued that early life adversity, such as adolescent alcohol or stress exposure, may prime the brain for accelerated aging and associated dysfunction ( Chaudhari et al, 2022 ). Few studies have attempted to directly link adolescent alcohol or stress exposure to lifespan cognitive decline due to obvious difficulties in tracking subjects across an entire lifespan, although some have argued for the high likelihood that early life adversity accelerates brain aging and decline ( Chaudhari et al, 2022 ). However, more research has separately examined the effects of adolescent alcohol or stress on early adult cognitive performance and its neurobiological correlates.…”