Skin aging is determined by a combination of endogenous and environmental influences, including epigenetic, posttranslational, microbial, and lifestyle factors. In particular genetic changes, programmed or not, play a pivotal role and understanding of these complex mechanisms may contribute to the prevention of age-related diseases and extension of healthy lifespan. In this article, new knowledge about genes and biological processes that can significantly affect skin homeostasis in old age and can lead to the typical morphological and physiological characteristics of aging skin are summarized.