The energetic stress cytokine GDF15 is elevated in the context of chronic and acute psychosocial stress.
Level 3 - non-randomized controlled study
Multi-cohort observational association studies combined with non-randomized acute laboratory stress experiments.
PubMed 38659958 · doi:10.1101/2024.04.19.590241
What was done
The authors investigated whether Growth Differentiation Factor 15 (GDF15), a marker of mitochondrial energetic stress, responds to psychosocial stress using observational and experimental designs. They analyzed plasma GDF15 in two large cohorts—the UK Biobank (n=53,026) and the Framingham Heart Study (FHS) Offspring cohort (n=3,460)—evaluating links to depression, anxiety, socioeconomic stressors, and epigenetic aging clocks. They also conducted an intensive saliva sampling study in 2 participants over 112 days and two laboratory acute social-evaluative stress experiments in 148 participants measuring plasma and saliva GDF15.
What was found
In both UK Biobank and FHS cohorts, plasma GDF15 was significantly elevated in participants with depression and anxiety symptoms. In FHS, GDF15 was higher among individuals with lower educational attainment, lower family income, and higher job strain, and it correlated positively with epigenetic clocks measuring biological aging. In the 2-participant intensive study, salivary GDF15 peaked at awakening and declined by 42% to 92% within 30 to 45 minutes. In the laboratory experiments (n=148), acute stress significantly increased GDF15 in plasma and saliva within minutes. Exact numerical effect sizes and p-values for cohort associations and experimental increases were not reported in the abstract.
Why it matters
This study links both acute and chronic psychosocial stress to GDF15, suggesting that psychological stress may directly induce mitochondrial energetic strain and accelerate biological aging. It also demonstrates that GDF15 can be measured non-invasively in saliva to track acute stress responses.
Limits
The large cohort analyses are observational, precluding causal inferences. The diurnal awakening response study included only 2 participants. The abstract does not report exact numerical effect sizes, test statistics, or confidence intervals for the cohort associations or the acute stress experiments. Finally, this record is a preprint that has not undergone peer review.
Cited by
- supports Acute laboratory psychosocial mental stress induces a measurable increase in circulating blood levels of GDF15.
- supports Data from the UK Biobank with 14 years of follow-up demonstrates that high baseline GDF15 levels are associated with higher rates of mental illness, cardiovascular disease, hypertension, and all-cause mortality.