SUMOylation is a reversible post-translational modification, where a small peptide (SUMO) is covalently attached to a target protein and changes its activity, subcellular localization and/or interaction with other macromolecules. SUMOylation substrates are numerous and diverse and modification by SUMO is involved in many biological functions, including the response to stress. The SUMO pathway has recently been implicated in the process of cellular senescence, the irreversible loss of cell replication potential that occurs during aging in vivo and in vitro. SUMO peptides, a SUMO E3 ligase and a SUMO-specific peptidase can induce or hinder the onset of senescence, thus supporting an association of SUMOylation with cell growth arrest and organismal aging. Preliminary results on comparative analysis ofproteomics and mRNA levels between young and old human and murine tissues show elevated levels of global protein SUMOylation and a decrease in components of the SUMOylation process with age. Further connections between the SUMO pathway and the aging process remain to be elucidated.