The long-term objective of this research is to investigate why there is a detrimental decrease in the synthesis rates of the mixture of all myocardial proteins as the heart ages. The immediate aims of this present project are: (1) to determine whether the synthesis rates of selected specific proteins (cytochrome c, actin, ribosomal proteins, collagen and alpha and beta myosin heavy chains) decrease during senescence. The rationale is that to determine the mechanism for the molecular control of gene expression in the aging heart, correlations must be made between the synthesis rates of specific proteins and the levels of their mRNAs.
Aim (2) is to correlate levels of protein synthesis and mRNA for these specific proteins in adult (1-yr old rat) and senescent (2-yr old rat) hearts. To determine whether a decreased capacity for the synthesis of these proteins is responsible for the decline in their content with aging in the heart, physical exercise and thyroxine will be used as experimental tools to enhance their synthesis. Therefore, aim (3) will be to determine if daily treadmill running will increase cytochrome c synthesis rate and also alter its mRNA level and profile in cardiac muscle.
Aims (4) and (5) will be to determine if there is any defect in the capacity of the senescent heart to synthesize specific proteins and to increase the levels of their mRNAs in response to thyroxine.
Aim (6) correlates the relationships between left ventricular pressure and dp/dt with the synthesis rates of specific proteins, specific mRNAs, age, thyroxine treatment and exercise. The synthesis rates of these proteins will be measured by the constant infusion of 3H leucine into unanesthesized rats in vivo. Specific mRNA levels will be determined in cardiac muscle by dot hybridization techniques using specific cDNA probes. Acute left ventricular cannulae will access pressures. This study will determine whether correlations exist between left ventricular pressures, aging, and factors (thyroxine and exercise) which cause volume overloading of heart and changes in the synthesis rates and mRNA levels of specific myocardial proteins. From such observations, future studies into the regulation of gene expression would be justified to determine the cause of the age- induced impairment in heart pumping capacity.
| Coppola, Jessica D; Horwitz, Barbara A; Hamilton, Jock et al. (2004) Expression of NPY Y1 and Y5 receptors in the hypothalamic paraventricular nucleus of aged Fischer 344 rats. Am J Physiol Regul Integr Comp Physiol 287:R69-75 |
| Biggs, R B; Hanley, R M; Morrison, P R et al. (1991) Cytochrome c mRNA levels decrease in senescent rat heart. Mech Ageing Dev 60:285-93 |
| Biggs, R B; Booth, F W (1990) Protein synthesis rate is not suppressed in rat heart during senescence. Am J Physiol 258:H207-11 |
