Naturally occurring decline in cardiovascular reserve with age associates with a combination of the reduction in
cardiomyocyte number and altered cardiomyocyte function. Recent investigations suggested that about half of the cardiomyocytes
is the same as at birth, while the other half of the cardiomyocytes is the result of cardiomyocyte renewal in the
senescent heart. In addition, the total number of cardiomyocytes is estimated to be less by one third in the old heart than
the number of cardiomyocytes at birth. Thus, the reduction in cardiomyocyte number of the aging heart cannot be fully
compensated by cardiomyocyte renewal. Aging of long-lived differentiated myocardial cells, as well as of cardiac progenitor
stem cells may contribute to an increased rate of apoptosis, and decreased capacity of cell duplication and/or differentiation.
In addition, differentiated cardiomyocytes are prone for accumulating biological by-products of cellular metabolism
and of incompletely processed oxidative insults. In this context, interactions between lysosomes and mitochondria
may provide a mechanistic background for the age-dependent alterations in cardiac macromolecules. This reasoning
postulates a direct relationship between the number of pro-oxidative, ill-functioning mitochondria and the amount of ballast-
overloaded lysosomes in long-lived cardiomyocytes. Accumulation of biological garbage and telomere shortening
might be considered as hallmarks of cardiomyocyte aging with implications for depressed cardiac function and cardiomyocyte
renewal. Changes in protein expression together with posttranslational modifications of myocardial proteins affect
excitation-contraction coupling and explain the declining mechanical function of the cardiomyocytes. Altogether,
these changes represent a significant part of the reduced cardiovascular reserve in aged individuals.