The Senescence Associated Secretory Phenotype, a key marker of cellular senescence, is elevated in depression and moderated by sex

Int Psychogeriatr. 2025 Jul 12:100113. doi: 10.1016/j.inpsyc.2025.100113. Online ahead of print.

ABSTRACT

OBJECTIVE: Studies have found elevation in a key biomarker of aging (the senescence-associated secretory phenotype (SASP) index) in depression. We investigated whether sex moderates the association between the SASP and major depression in older adults.

METHODS: We included 423 older adults in a current major depressive episode and 140 adults with no history of depression. We measured the plasma levels of SASP biomarkers using multiplex immunoassays. The interaction effect between sex, depression diagnosis, and senescence markers were analyzed by general linear models, adjusted for confounding variables.

RESULTS: Individuals with depression had a higher SASP index than the healthy comparison group (t-test= -3.902, p < 0.001). We found a significant diagnosis by sex interaction (F= 9.112, df= 1540, p = 0.003), with males with depression having the highest SASP index levels (F=20.678, df=1540, p < 0.001).

CONCLUSIONS: In older adults, sex plays a significant role in senescence-related changes in depression. A higher senescence burden in males with depression may be an indicator of greater vulnerability to accelerated biological aging and a marker of elevated risk of adverse outcomes in this sex.

PMID:40653403 | DOI:10.1016/j.inpsyc.2025.100113