IP₃ Receptors, Mitochondria, and Ca²⁺ Signaling: Implications for Aging

Figure 2

Altered Ca²⁺ signaling during aging and in age-related diseases. The Ca²⁺ dyshomeostasis during age is dependent on the cell type and the context. Most aged cells display decreased ER Ca²⁺ content and release, due to declined IP₃R or RyR levels, reduced SERCA activity, and decreased Ca²⁺ buffering by intraluminal Ca²⁺-binding chaperones. However, in neurons and rat hearts, an enhanced Ca²⁺ signaling is found, caused by increasing IP₃R or RyR activity. Age-related diseases (neurodegeneration, cardiac hypertrophy, and chronic heart failure) are also characterized by enhanced Ca²⁺ signaling. However, this property may be disease dependent, since a mouse model for Huntington’s disease displayed attenuated IP₃R1 activity due to impaired binding of Grp78 to IP₃R1. Hence, caution should be taken with general claims.