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The “Heartbreak” of Older Age
Table 2.
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 | ||
