Consequences of aging on the adaptative capacity of Microcebus murinus heart to stress
Résumé
Aging is an important risk factor for cardiovascular disease. Regardless of lifestyle,
aged people are subject to a decrease in maximal heart rate (HR) and in HR
Variability (HRV). Mechanisms underlying the decrease in HR and HRV and the
consequences on body physiology are still unclear.
Objective
Our objective is to study the effect of aging on the regulation of and its
modulation by the neuronal environment that modulates HR in aged patients.
Method
To study HR and HRV, we used the small primate Microcebus murinus (ML), which
generates 3 billion heartbeats in a lifetime, as humans (three times more than
mice). To record cardiac activity, we developed a jacket to record surface ECGs in
young (1-5 years) and aged (6-12 years) animals of both genders, under stressful
condition and 3 hours after.
Results
First, we confirmed that HR was decreased 3h post-stress vs. stress in young
females (11.5%, p*=0.01) and also in young males (great tendency: 8%, p=0.06).
Conversely, no changes were observed in aged MLs (p=ns) both genders. The
analysis of the Coefficient of Variability of RR intervals (CVRR), which mainly
reflects sympathetic tone, showed that under stress it was higher in aged vs.
young MLs (46%, p*=0.03), suggesting an impaired response to stress (loss of β-
adrenergic regulation). Despite this difference, the CVRR was increased 3h after
stress in young (males, 80 %, p***=0.0007; females, 76%, p*=0.01) and aged
(males, 55%, p*=0.04; females, 61% p*=0.03) animals of both genders, compared
with the stress condition, as expected. However, the RMSSD (Root Mean Square
of Successive Differences between normal heartbeats), an index of the
parasympathetic tone, was increased in young (males, 65%, p*=0.04; females,
66%, p*=0.03) but was unchanged in aged MLs (males, 23%; p=ns; females, 40%,
p=ns), suggesting that the difficulty to recover from stress was related to an
impaired vagal modulation in aged animals.
Conclusion
Our results show that cardiac activity was not able to adapt to stress response
due to aging through a β-adrenergic and vagal impairment. For the first time,
these results pave the way to the understanding of why HRV decreases in aged
patients.