TY - JOUR
KW - Ageing
KW - Experimental models of disease
KW - Lab-on-a-chip
KW - Metabolic diseases
KW - Stem-cell biotechnology
AU - Lin Qi
AU - Yuchen He
AU - Alexandra Sviercovich
AU - Xiaoyue Mei
AU - Erzhen Chen
AU - Yihan Xia
AU - Michael J. Conboy
AU - Irina M. Conboy
AU - Andreas Stahl
AB - 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.
BT - Nature Biomedical Engineering
DA - 2026-03-25
DO - 10.1038/s41551-026-01618-6
LA - en
N2 - 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.
PY - 2026
SP - 1
EP - 18
T2 - Nature Biomedical Engineering
TI - Human microphysiological systems of aging recreate the in vivo process expediting evaluation of anti-geronic strategies
UR - https://www.nature.com/articles/s41551-026-01618-6
Y2 - 2026-04-14
SN - 2157-846X
ER -