To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling >20 million cells from 623 mouse tissues across different life stages, sexes, and genotypes. This comprehensive dataset reveals >3000 different cellular states and >200 aging-associated cell populations. Our panoramic analysis uncovered organ-, lineage-, and sex-specific shifts in cellular dynamics during life-span progression. Moreover, we identify both systematic and organ-specific alterations in immune cell populations associated with aging. We further explored the regulatory roles of the immune system on aging and pinpointed specific age-related cell population expansions that are lymphocyte dependent. Our "cell-omics" strategy enhances comprehension of cellular aging and lays the groundwork for exploring the complex cellular regulatory networks in aging and aging-associated diseases.