Human and other multi‐cellular life species age and the aging processes become dominant in a late phase of lives. However, recent studies challenged the dogma suggesting that ageing in some animal species may never occur, but mammals undertake cell replicative senescence as early as before birth in embryos under physiological conditions. How the molecular machineries operate, and why aging cells dominate under some circumstances, are intriguing. Recent studies show that cell aging involves extensive cellular remodeling, including telomere attrition, heterochromatin formation, endoplasmic reticulum stress, mitochondrial disorders, lysosome processing organelles and chromatins. This article provides an update in the molecular mechanisms underlying aging of various cell types, the newly described developmental and programmed replicative senescence, and the critical roles of cellular organelles and effectors in Parkinson's disease, diabetes, hypertension and dyskeratosis congenita. This article is protected by copyright. All rights reserved.