scCamAge: A context-aware prediction engine for cellular age, aging-associated bioactivities, and morphometrics.

Current deep-learning-based image-analysis solutions exhibit limitations in holistically capturing spatiotemporal cellular changes, particularly during aging. We present scCamAge, an advanced context-aware multimodal prediction engine that co-leverages image-based cellular spatiotemporal features at single-cell resolution alongside cellular morphometrics and aging-associated bioactivities such as genomic instability, mitochondrial dysfunction, vacuolar dynamics, reactive oxygen species levels, and epigenetic and proteasomal dysfunctions. scCamAge employed heterogeneous datasets comprising ∼1 million single yeast cells and was validated using pro-longevity drugs, genetic mutants, and stress-induced models. scCamAge also predicted a pro-longevity response in yeast cells under iterative thermal stress, confirmed using integrative omics analyses. Interestingly, scCamAge, trained solely on yeast images, without additional learning, surpasses generic models in predicting chemical and replication-induced senescence in human fibroblasts, indicating evolutionary conservation of aging-related morphometrics. Finally, we enhanced the generalizability of scCamAge by retraining it on human fibroblast senescence datasets, which improved its ability to predict senescent cells.