The energetic cost of allostasis and allostatic load.

Chronic psychosocial stress increases disease risk and mortality, but the underlying mechanisms remain largely unclear. Here we outline an energy-based model for the transduction of chronic stress into disease over time. The energetic model of allostatic load (EMAL) emphasizes the energetic cost of allostasis and allostatic load, where the “load” is the additional energetic burden required to support allostasis and stress-induced energy needs. Living organisms have a limited capacity to consume energy. Overconsumption of energy by allostatic brain-body processes leads to hypermetabolism, defined as excess energy expenditure above the organism’s optimum. In turn, hypermetabolism accelerates physiological decline in cells, laboratory animals, and humans, and may drive biological aging. Therefore, we propose that the transition from adaptive allostasis to maladaptive allostatic states, allostatic load, and allostatic overload arises when the added energetic cost of stress competes with longevity-promoting growth, maintenance, and repair. Mechanistically, the energetic restriction of growth, maintenance and repair processes leads to the progressive wear-and-tear of molecular and organ systems. The proposed model makes testable predictions around the physiological, cellular, and sub-cellular energetic mechanisms that transduce chronic stress into disease risk and mortality. We also highlight new avenues to quantify allostatic load and its link to health across the lifespan, via the integration of systemic and cellular energy expenditure measurements together with classic allostatic load biomarkers.

慢性心理社会应激会增加疾病风险和死亡率，但其潜在机制在很大程度上仍不明确。在此，我们概述了一个基于能量的模型，用于解释慢性应激如何随时间推移转化为疾病。稳态负荷的能量模型（EMAL）强调了稳态和稳态负荷的能量成本，其中“负荷”是支持稳态和应激诱导的能量需求所需的额外能量负担。生物体消耗能量的能力是有限的。稳态的脑 - 体过程过度消耗能量会导致代谢亢进，即超出生物体最佳状态的能量消耗过剩。反过来，代谢亢进会加速细胞、实验动物和人类的生理衰退，并可能推动生物衰老。因此，我们提出，当应激的额外能量成本与促进长寿的生长、维持和修复过程相互竞争时，就会出现从适应性稳态到适应不良的稳态、稳态负荷以及稳态超负荷的转变。从机制上讲，生长、维持和修复过程的能量受限会导致分子和器官系统的渐进性损耗。所提出的模型围绕将慢性应激转化为疾病风险和死亡率的生理、细胞和亚细胞能量机制做出了可检验的预测。我们还强调了通过整合全身和细胞能量消耗测量以及经典的稳态负荷生物标志物，在整个生命周期中量化稳态负荷及其与健康的联系的新途径。