Acute cold exposure in humans shifts the circulating proteome to a cardioprotective and anti-aging profile

Plucinska, K.; Chen, Z.-Z.; Xiang, R.; Zaman, S.; Yan, L.; Hurson, C.; Peterson, C.; Fredrickson, K.; Farrell, L.; Walker, J.; Kars, M. E.; Tiwari, G.; Pourquie, O.; Itan, Y.; Carroll, T.; Chen, K. Y.; Cypess, A. M.; Gerszten, R. E.; Cohen, P.

doi:10.1101/2025.06.30.662436

bioRxiv · 10.1101/2025.06.30.662436

Acute cold exposure in humans shifts the circulating proteome to a cardioprotective and anti-aging profile

Plucinska, K.·Chen, Z.-Z.·Xiang, R.·Zaman, S.·Yan, L.·Hurson, C.·Peterson, C.·Fredrickson, K.·Farrell, L.·Walker, J.·Kars, M. E.·Tiwari, G.·Pourquie, O.·Itan, Y.·Carroll, T.·Chen, K. Y.·Cypess, A. M.·Gerszten, R. E.·Cohen, P.

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Abstract

Cold exposure has been proposed to provide a constellation of salutary effects, yet its molecular correlates remain largely unknown. Brown adipose tissue (BAT) is the main site of adaptive thermogenesis, and its prevalence is linked with cardiometabolic health. Since the benefits of BAT activation and cold exposure more generally may be mediated through blood-borne factors, we conducted an extensive analysis of the circulating proteome linked with an acute cold challenge in healthy adults. Our goal was to uncover early molecular changes triggered by cooling and establish their specific relationships with the human brown adipocyte secretome as well as various phenotypic traits. Based on comprehensive inter-cohort validations, we provide the first reproducible proteomic signature of cold exposure in humans. Our data demonstrate that cooling favorably modulates circulating mediators linked with chronological aging, as well as metabolic and cardiovascular diseases, providing new potential biochemical transducers of the benefits associated with cold therapy. HighlightsO_LICooling alters the plasma proteome with striking concordance in independent human cohorts. C_LIO_LICooling represses circulating proteins linked with type 2 diabetes, hypercholesterolemia, hypertension, coronary heart disease and heart failure. C_LIO_LIThe circulating signature of cooling resembles a cardioprotective and anti-aging profile. C_LI

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Plucinska, K., Chen, Z.-Z., Xiang, R., Zaman, S., Yan, L., Hurson, C., Peterson, C., Fredrickson, K., Farrell, L., Walker, J., Kars, M. E., Tiwari, G., Pourquie, O., Itan, Y., Carroll, T., Chen, K. Y., Cypess, A. M., Gerszten, R. E., Cohen, P.. 2025-07-04. Acute cold exposure in humans shifts the circulating proteome to a cardioprotective and anti-aging profile. https://doi.org/10.1101/2025.06.30.662436

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