Aging is a universal trait that is characterized by a progressive loss of physiological integrity, leading to declined function in tissues and increased vulnerability to disease and death. It has been long hypothesized that the functional decline in aging is caused by genome instability. The general interest of the Zhang Laboratory focuses on the somatic genome and epigenome instability in aging and longevity. More specifically we study somatic DNA mutations and epi-mutations and their effects on cellular functional decline in normal aging process or age-related diseases. We have been developing experimental approaches of single-cell multi-omics and applying them to discover interactions of genome, transcriptome and epigenome in individual cells from different tissues of humans during aging or species with different maximum life spans.