Myocardial Changes With Adult Aging In Rodents
Structural Change | Functional Change | Ionic, Biophysical/Biochemical Mechanisms | Genetic Mechanisms |
---|---|---|---|
SR, sarcoplasmic reticulum; SERCA, Sarco/endoplasmic reticulum calcium ATPase; MHC, myosin heavy chain; RXR, retinoid X receptor; β AR, β -adrenergic receptor; AC, adenylyl cyclase; BARK, β -adrenergic receptor kinase; Gi , inhibitory G protein; TNI, troponin-I; ICa , calcium influx; Cai , intracellular calcium concentrations, HSF, heat shock factor; RYR2, cardiac ryanodine receptor, AT1R, Angiotensin II type 1 receptor; RAS, Renin-Angiotensin system. | |||
↑ Myocyte size | Prolonged Contraction | Prolonged cytosolic Ca2+ transient | |
↓ Myocyte number | ↓ SR Ca2+ pumping rate | SERCA mRNA | |
↓ Pump site density | No Δ calsequestrin mRNA | ||
Prolonged Action Potential | ↓ ICa inactivation | Na+ -Ca2+ exchanger mRNA | |
↓ ITo density | |||
Diminished Contraction | ↓α MHC protein | ↓ MHC mRNA | |
Velocity | ↑β MHC protein | ↑β MHC mRNA | |
↓ Myosin ATPase activity | No Δ Actin mRNA | ||
↓ RXRβ 1 and γ mRNA | ↓ RXRβ 1 and γ mRNA | ||
↓ RXRβ 1 and γ protein | |||
↓ Thyroid receptor protein | |||
Diminished β -adrenergic | ↓ Coupling β AR-AC | β1 AR mRNA | |
Contractile Response | No Δ Gi activation | no Δ BARK mRNA | |
No Δ β ARK activity | |||
↓ TNI, phospholamban | |||
↓ Phospholamban phosphorylation | |||
↓ ICa augmentation | |||
↓ Cai transient augmentation | |||
↑ Enkephalin peptides | |||
↑ Proenkephalin mRNA | |||
↑ Matrix connective tissue | ↑ Myocardial Stiffness | ↑ Hydroxyproline content | ↑ Collagen mRNA |
↑ Activity of myocardial RAS | ↑ Fibronectin mRNA | ||
↑ AT1R mRNA | |||
↑ Atrial naturetic peptide | ↓ Atrial naturetic peptide mRNA | ||
↓ Growth Response | ↓ Induction of immediate early genes | ||
↓ Heat Shock Response | ↓ Activation of HSF |