To read this article with accompanying illustrations, as well as all the articles in the series, you can go to the mini-site: "Aging of Your Heart and Blood Vessels is Risky" by clicking here.

Introduction

In the previous article, (" Brain Heart Communication Withers with Aging"), we learned that a division of the central nervous system, the autonomic nervous system, sends signals to the heart to acutely modify its behavior by releasing messenger substances called neurotransmitters. We talked about one particular neurotransmitter, norepinephrine, an adrenaline-like substance elaborated by the beta-adrenergic system. This substance is produced when the body is stressed, such as during exercise. It causes your heart to beat faster and stronger. This article will discuss what happens to this communication with aging.

Aging Effects on Brain-Heart Communication

With aging, this brain-heart communication by means of "messenger substances" becomes partially blocked. This is not because of insufficient production of neurotransmitter messengers, but rather because of an inability of the heart's cells to respond to the messengers. It can be compared to ordering from a mail-order catalogue. The packages arrive at your door, but at the time that they arrive no one is there to open the door and take them inside. This brings us to a discussion of how the old heart receives its "packages" of neurotransmitters and why this effect is blunted with aging.

The Doorman: Heart Cell Receptor Signaling

The heart contains nearly 5 million contractile muscle cells called cardiac myocytes. The membrane on the surface of each cell is lined with protein molecules called receptors. There are hundreds of different types of receptors on a cell's surface membrane; however, each receptor is unique and recognizes "specific" messenger substances. One type of receptor recognizes only the neurotransmitter molecules. This aspect of receptors, i.e. recognizing only "specific" messengers, can be compared to a doorman at an apartment building who is authorized to accept certain deliveries. Think of a heart cell's surface membrane as comparable to an apartment building. All the apartments in the building have the same street address (the cell), but each apartment in the building has it's own doorman (the unique receptor) for entry and deliveries of packages addressed specifically to that apartment.

"The Messengers"- Specific Beta-Adrenergic Receptor Signaling Molecules

Specific beta-adrenergic receptor signaling messenger molecules, norepinephrine (noradrenaline), are released from nerve endings near the heart's myocytes, or reach the heart's cells from the blood. These messenger molecules seek out and bind to specific beta-adrenergic receptors that are their "doorways" to enter the cell. This "activates" the receptors by causing them to change their configuration slightly.

Activation allows the receptors to connect with other specific proteins beneath the cell's membrane. Essentially it's like turning the key and unlocking the deadbolt to one of our apartments. The opened doorway (the reconfigured receptor) then becomes a receiving area, called a docking site, for identical signaling molecules (similar packages). Next, this receptor connection at the docking site sets off a chain of biochemical reactions within the cell that activates or deactivates proteins. These reactions govern various aspects of the cell's function.

Remembering the Role of Calcium

Schematically speaking, the process of activation or deactivation of proteins beneath the heart's cell membrane causes these proteins to link together to cause changes in cell behavior. We learned previously that calcium channels on the heart cell's membrane surfaces are shifted into high gear after the beta-adrenergic receptor is activated. This allows more calcium to enter the cells, and fill the calcium storage bins to a greater extent. This movement of calcium in and out of the heart cells, called calcium cycling, is the essence of the "heart beat". See (" The Essence of the Heartbeat Changes with Aging").

Beta Adrenergic Receptor Activation

1. Norepinephrine binds to beta-adrenergic receptors
2. Beta-adrenergic receptors are activated
3. Chain reaction occurs that modifies the hearts cells calcium cycling
4. Calcium channels can open more effectively
5. More calcium can enter the cell
6. Increased calcium entering the cell leads to a stronger and more rapid contraction

A similar process takes place at the heart's pacemaker, that group of cells in the top part of the heart that initiates the signal for the heart to beat and thus determines the heart rate. Beta-adrenergic receptor activation of the pacemaker cells causes their signals to be emitted at a faster rate. When the pacemaker fires faster the result is an increase in the heart rate.

The Receptor Signaling Pathway Can Fail

This beta-adrenergic receptor signaling pathway (or that of any of the other hundreds of specific receptor signaling pathways) can fail if any links in the chain reaction become weak. Over the long haul the body's needs dictate the effectiveness of receptor mediated cell signaling by adjusting the number of receptors or intracellular molecules that link receptors to specific intracellular biochemical pathways. For example, the numbers of beta-adrenergic receptor signaling pathways are regulated around the time of birth, during development, and in response to physical conditioning or prolonged bed rest. And, of importance to our discussions in these articles, the beta-adrenergic receptor signaling pathways are regulated in conjunction with cardiovascular disease and during aging.

Beta-Adrenergic Receptor Signaling Pathways Are Regulated by Body's Needs

Around the time of birth
During development
In response to physical conditioning
During prolonged bed rest
In conjunction with cardiovascular disease
During aging

When the Brain Talks to the Heart, "Age" Makes a Difference!

With aging, the number of beta-receptors is only modestly reduced. The main blockage of the beta-receptor signaling system is due to the failure of the activated beta-receptor to dock to the sub-membrane molecules inside the heart cells and activate the biochemical chain reaction that regulates calcium. With a less robust chain reaction the beta signaling pathway becomes "desensitized".

How does a "desensitized" beta signaling pathway affect the older person's heart?

One example is that during stress, such as vigorous exercise, the cell response is partially blocked, and thus the expected "exercise-induced" increase in heart rate and strength of heart contraction is not achieved. This happens even though the older person produces sufficient neurotransmitters to stimulate their hearts' beta-adrenergic receptors. It's the failure of the heart's beta-adrenergic signaling with aging, not the production of neurotransmitters, that's the major reason why the hearts of older persons, relative to younger persons, dilate and beat less rapidly during vigorous exercise. The end result is a reduction in cardiac reserve which reduces the older person's fight or flight reaction. (" Brain Heart Communication Withers with Aging")

The next article in our series will be "What Was Once Believed To Be Normal Aging Is Now Considered To Be Dangerous!" It will focus primarily on blood pressure changes that were once considered normal with aging, which have now been determined to be harmful to healthy aging.

Dr. Ed is a physician/scientist, who is internationally recognized for studies that range from humans to molecules on how the heart and blood vessels work in health and disease as the body ages.