Myocardial adaptations in advanced age

Area of Science:

• Cardiovascular Physiology
• Aging Biology
• Cellular Cardiology

Background:

• Arterial stiffening and increased systolic pressure are hallmarks of aging in humans.
• The aging heart shows left ventricular wall thickening and myocardial cell enlargement as adaptations.
• Cellular studies in animal models reveal a prolonged excitation-contraction coupling cycle with aging.

Purpose of the Study:

• To investigate the cellular mechanisms underlying age-related cardiovascular changes.
• To understand how cellular calcium handling is altered in the aging heart.
• To examine the impact of aging on cardiac response to stress and beta-adrenergic stimulation.

Main Methods:

• Analysis of cellular calcium (Ca2+) cycling in animal models.
• Investigation of transcriptional regulation of sarcoplasmic reticulum Ca2+ pump density.
• Assessment of beta-adrenergic stimulation effects on cardiac function in aging.
• In situ studies of cardiac adaptation during stress in older animals and humans.

Main Results:

• Aging prolongs the cytosolic calcium transient, enhancing force-bearing capacity for ejection into stiff arteries.
• Reduced sarcoplasmic reticulum Ca2+ pump gene expression leads to slower Ca2+ removal from the cytosol.
• Older humans exhibit diminished heart rate and contractility increases under stress due to reduced beta-adrenergic stimulation efficacy.
• Cardiac dilatation occurs during stress in older hearts, maintaining stroke volume.

Conclusions:

• Age-related cardiovascular changes involve cellular adaptations in calcium handling and response to stress.
• Transcriptional downregulation of Ca2+ pumps contributes to altered cellular Ca2+ dynamics in aging.
• Despite reduced adrenergic response, cardiac adaptations like dilatation maintain function in older individuals.
• Chronic pressure overload accelerates these age-related cardiovascular adaptations.