Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases

Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca²⁺ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca²⁺/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca²⁺/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca²⁺/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.