Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory/bench study using human cell culture lines.
PubMed 37423094 · doi:10.1016/j.psyneuen.2023.106322
What was done
Researchers longitudinally profiled three unrelated primary human fibroblast cell lines across their lifespan during chronic glucocorticoid exposure to model cellular allostatic load. They evaluated changes in cellular energy expenditure, metabolic shifts between glycolysis and mitochondrial oxidative phosphorylation (OxPhos), mtDNA stability, cytokine secretion, DNA methylation clocks, telomere shortening rates, and overall cellular lifespan, including testing pharmacological normalization of OxPhos activity.
What was found
Chronic glucocorticoid exposure increased cellular energy expenditure by ~60% and shifted cellular metabolism from glycolysis toward OxPhos. This stress-induced hypermetabolism was linked to mtDNA instability, altered age-related cytokine secretion, and accelerated cellular aging, reflected by accelerated DNA methylation clocks, faster telomere shortening, and shortened cellular lifespan. Pharmacologically normalizing OxPhos while further increasing energy expenditure exacerbated the accelerated aging phenotype.
Why it matters
This study provides cellular-level evidence connecting chronic stress-hormone signaling to hypermetabolism and accelerated biological aging, pointing to elevated cellular energy expenditure as a possible driver of allostatic load.
Limits
The study is restricted to an in vitro model utilizing only three primary fibroblast lines, which does not capture complex systemic neuroendocrine interactions, tissue-specific differences, or whole-organism physiology. Specific statistical parameters, dosage concentrations, and confidence intervals were not reported in the abstract.
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