INTRODUCTION Cellular senescence is involved in important biological processes, e.g., development, aging, and tumorigenesis, and is induced by activation of the p53-21 WAF1 or p16 INK4a-pRB axis [1]. Repression of p16 INK4a expression delays senescence and regulates the replicative senescence phenotype [2]. Expression of p16 INK4a is regulated by complex pathways involving lymphoid-specific helicase (Lsh), which binds to the p16 INK4a promoter and creates a repressive chromatin structure by recruiting HDAC1 [3]. The free-radical theory of aging [4] proposes that progressive accumulation of mitochondrial dysfunction in aged cells might be due to increased production of reactive oxygen species (ROS). Not only in senescent cells, but also in vivo skeletal muscle, mitochondrial bioenergetics and mitochondrial membrane potential differences (Δψm) are significantly impaired in aged www.aging-us.com