Human microphysiological systems of aging recreate the in vivo process expediting evaluation of anti-geronic strategies.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The search for biological mechanisms of human aging is stalled by a lack of suitable models, and it remains unknown whether and to what degree rejuvenation reported in rodents translates to people. Here we report a human induced pluripotent stem cell-derived microphysiological system modelling the white adipose tissue-liver axis in the presence of heterochronic human serum to study aging and rejuvenation in humans. We reveal changes in functional and molecular hallmarks of aging and rejuvenation. We also investigate unknown biomarkers and mechanisms of plasticity in human tissue aging and potential rejuvenation strategies. The microphysiological chip recapitulates, in 4 days, aging-associated hallmarks that occur after decades of aging in people, including gerontic shifts in gene expression and oxidative DNA damage. We uncover unknown signalling networks in human aging, knock-on effects of aging in fat on liver, sexual polymorphisms of aging and tissue memory of age, and develop a custom machine learning model for biological age. Combining heterochronic human serum with the microphysiological system allows for rapidly establishing human tissue aging, discovering clinically relevant mechanisms and biomarkers, and testing of anti-geronic approaches.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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