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Age and the Diurnal Oscillatory Features of the Human Chronobiome

Skarke, C.; Lahens, N. F.; Mrcela, A.; Olsson, N.; Glessner, J.; Naik, A.; Theken, K. N.; Chivily, C.; Douglas, D.; Hess, K. N.; Gaun, A.; Moustafa, A. M.; Daniel, S. G.; Bittinger, K.; Teegarden, S.; Lordan, R.; El Jamal, N.; Meng, H.; Hollingsworth, T.; Woolfork, A.; Sengupta, A.; Brooks, T. G.; Weljie, A.; Grant, G.; O'Brien, J.; McAllister, F.; Melamud, E.; FitzGerald, G. A.

2026-01-23 cardiovascular medicine
10.64898/2026.01.21.26344528 medRxiv
Show abstract

The molecular clock regulates diverse aspects of human biology. As people age, diurnal rhythms deteriorate, most evidently in the daytime napping and nighttime waking of older individuals. To understand how temporal deconsolidation of oscillatory networks could contribute to age-related disease expression, we studied the chronobiome at unprecedented depth in young and old apparently healthy individuals. Transomic integration segregated age groups and identified candidate mechanisms by which oscillatory function might contribute to age dependent distinctions. In an orthogonal approach, we validated as true cyclers many proteins identified in the UK Biobank as predictors of health and disease outcomes. Here, age-specific alterations in the cycling proteome across disease phenotypes is consistent with our hypothesis that deconsolidated circadian programs associate with increased susceptibility to age-related disease.

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