"He is the best physician who is the most ingenious inspirer of hope." Samuel Taylor Coleridge, English Poet and Philosopher, 1772-1834 In 1903, Dutch physiologist Willem Einthoven, MD, PhD invented the electrocardiograph, a machine that measures the minute electrical currents generated by the heart. Initially, it was a cumbersome and costly device, taking five technicians to operate. During the procedure, patients had to place both hands and both feet in buckets of water.But as a result of this advance cardiologists began, for the first time, to fully understand the electrical processes involved in generating the heart beat.With this knowledge, they were able to more precisely diagnosis certain cardiovascular problems.

Willem Einthoven,MD,PhD, Dutch physiologist.

No doubt about it, doctors know more about the heart and how to keep it healthy than at any other time in history. In just the past 30 years, gerontologists have revolutionized ideas about what happens in the older heart. They’ve learned, for instance, that age-related changes in the structure and function of the heart occur in virtually every person.Mounting evidence suggests that some of these changes, previously thought to be a part of normal aging, precede and predict the onset of cardiovascular diseases, even among those who do not yet have signs or symptoms of disease. But they’ve also learned that preventive measures, such as getting regular exercise, eating a healthy diet, and not using tobacco, can have a profound impact on the aging cardiovascular system.

In the future, interventions to slow accelerated aging of the heart and arteries in apparently healthy young and middle-age people could prevent or delay the onset of heart disease, stroke, and other cardiovascular disorders in later life, Dr. Lakatta says. These interventions may take many forms. For instance, the more we understand about the changes that take place in cells and molecules during aging, the closer we get to the possibility of designing drugs targeted to those changes. Gene therapies can also target specific cellular changes and could potentially be a way to intervene in the aging process.

Achieving these goals will likely require considerable effort and as much, or perhaps even more, ingenuity and innovation in the coming years as has been shown in the past. NIA investigators and others are already taking steps to meet these challenges. They still have many questions to answer and mysteries to solve. But as this work progresses and scientists unravel more of the aging heart’s secrets, the hope of forestalling cardiovascular disease and improving the quality of life for older people may come closer to reality.

Glossary

ADVENTITIA – The outermost layer of arterial wall; it is composed of connective tissue.

AFTERLOAD – The mechanical load encountered by the heart following the onset of contraction; the forces that resist the flow of blood from the heart. The afterload may increase with age due to increasingly stiff arteries and an increased tone of the smaller arteries.

ANGIOTENSIN – A chemical that constricts blood vessels, which raises blood pressure.

AORTA – The largest artery in the body. It conducts blood away from the heart, then branches into many smaller arteries that take blood to the rest of the body. The diameter of the aorta enlarges with age and its walls become stiffer.

ARTERIES – Blood vessels that carry blood away from the heart to all parts of the body. Some enlarge with age and become thicker and stiffer. Arterial walls consist of three layers: the intima, media, and adventitia.

ARTERIOLES – The very small arteries that take blood from the arteries to the capillaries.

ATHEROSCLEROSIS – A condition of the arteries in which the interior of the artery wall is made thick and irregular by deposits of fatty substances and invasive cells from the blood and arterial wall and matrix substances synthesized by the cells.

ATRIOVENTRICULAR NODE – A group of special conduction fibers at the base of the wall between the right atrium and ventricle. They relay the electrical impulses to the ventricle to initiate contraction. These electrical impulses originate in the heart’s pacemaker, the sinoatrial node within the right atrium.

ATRIUM – One of the two upper chambers of the heart. The right atrium receives blood depleted of oxygen from the veins; the left atrium receives blood with fresh oxygen from the lungs. The left atrial cavity enlarges with age.

AUTONOMIC NERVOUS SYSTEM – That part of the nervous system that controls involuntary muscles, such as the heart. It uses chemicals, such as catecholamines, to send messages from the brain to the heart.With age, the body’s response to cathecholamines withers.

BARORECEPTOR RESPONSE – The body’s response to pressure sensitive nerves in the carotid artery that help regulate heart rate and arterial pressure; the response grows weaker with age.

BLOOD PRESSURE –The force that flowing blood exerts against artery walls. Systolic blood pressure occurs when the heart contracts and pumps blood into the aorta. Diastolic blood pressure occurs when the aortic valve closes and the heart relaxes and refills with blood.

CALCIUM PUMP PROTEINS – Proteins on the sarcoplasmic reticulum that remove calcium from the cell cytosol after a contraction. The number of these pump proteins declines with age.

CALCIUM TRANSIENT – The transient increase in calcium in the cytosol following excitation, which causes a contraction. It grows longer with age.

CAPILLARIES – The smallest blood vessels that take blood from the arterioles to cells in the body.

CARDIAC CYCLE – The cycle of synchronized activities that occurs during one heart beat.

CARDIAC OUTPUT – The amount of blood a heart pumps each minute. It is calculated by multiplying heart rate by stroke volume.

CARDIOVASCULAR – Of or pertaining to the heart and blood vessels.

CHEMOKINES – A type of cytokine that carries messages between cells. In a sense, they tell cells where to go. If chemokines are increased in a particular tissue, such as an artery, the cell with the receptor, or partner, for that particular molecule is attracted to move into that tissue.

CHOLESTEROL – A waxy, fat-like substance present in cell walls or membranes everywhere in the body, including the heart. Excess cholesterol is deposited in arteries, including the coronary arteries, where it contributes to the narrowing and blockages that cause the signs and symptoms of heart disease. Cholesterol is carried in small packages called low density (LDL) and high density (HDL) lipoproteins.

CONTRACTILE (MYOFILAMENT) PROTEINS – Proteins in myocytes that change their configuration in order to bring about a shortening or contraction of the cell. This may change with age.

CONTRACTILE STATE – The ability of the heart muscle cells to contract, also referred to as contractility.

CORONARY HEART DISEASE – Also called coronary artery disease ischemic heart disease. A narrowing of the coronary arteries due mostly to atherosclerosis resulting in a decreased flow of blood to the heart muscle and thus lower levels of oxygen reaching the heart.

ECHOCARDIOGRAM (ECG OR EKG) – A visual record of the heart’s electrical activity.

EJECTION FRACTION – The fraction of end diastolic volume pumped out with each beat.

ELECTROCARDIOGRAPHY – A method of graphically recording the structure and movement of the heart by the echo caused by beams of ultrasonic waves.

END DIASTOLIC VOLUME – The volume of blood in the left ventricle at the end of diastole, just before the next beat.

ENDOTHELIUM – The smooth inner lining of many body structures, including the heart and blood vessels. Endothelial cells are a primary component of the intima.

END SYSTOLIC VOLUME – The volume of blood left in the heart at the end of the heartbeat.

ENZYME – A protein that promotes a specific biochemical reaction in the body without itself being permanently changed or destroyed. Enzymes may have an important role in the ageassociated changes in structure and function that occur in the heart and arteries.

FRANK-STARLING LAW OF THE HEART – A phenomenon in which the more the heart muscle is stretched the more vigorously it contracts.

FREE RADICALS – Molecules with unpaired electrons that react readily with other molecules. Free radicals can damage myocytes as well as the membranes and DNA of endothelial cells in the intima and smooth muscle cells in the media. This damage can promote stiffening and thickening of arterial walls. Free radicals also can contribute to atherosclerotic plaque build up.

GENE – A segment of DNA that codes for a specific protein or other molecule. Each gene contains a specific sequence of chemicals. The sequence is referred to as a “code” because it specifies the order of amino acids (chemical building blocks of proteins) in the end product.

GENE EXPRESSION – The process by which the information contained in genes is transcribed and translated into proteins. Age-related changes in gene expression may account for some changes in heart and artery function.

HEART ATTACK – The death of a portion of heart muscle, resulting when an obstruction in one of the coronary arteries prevents an adequate oxygen supply to that muscle. Heart attacks may be referred to in terms of obstruction (coronary thrombosis) or in terms of the damage done (myocardial infarction).

HEART FAILURE – A condition in which the heart is unable to pump the amount of blood needed by the body. Heart failure can develop from many heart and circulatory disorders, such as high blood pressure heart attack. It often leads to congestion in the body tissues, with fluid accumulating in the abdomen and legs and/or in the lungs. This condition is often called congestive heart failure.

HEART RATE – The number of beats per minute.

HIGH BLOOD PRESSURE – An unstable or persistent elevation of blood pressure above the normal range. Blood pressure often increases with age. High blood pressure increases the risk of heart disease and stroke; also known as hypertension.

HIGH DENSITY LIPOPROTEINS (HDL) – The "good" cholesterol. HDL carries cholesterol in the blood from other parts of the body back to the liver, which leads to its removal from the body. HDL helps keep cholesterol from building up in the walls of the arteries.

HYPERTROPHY – Enlarge or enlargement. The myocytes that make up the walls of the heart hypertrophy with age.

ISCHEMIA – Decreased blood supply to the heart muscle.

INTIMA – The innermost layer of arterial wall closest to the blood. It is composed of a single layer of specialized cells, called endothelial cells, which sit atop the sub-endothelial space and a wall called the basement membrane.

LOW DENSITY LIPOPROTEIN (LDL) – The “bad” cholesterol.High LDL cholesterol leads to a build up of cholesterol in arteries. The higher the LDL level in your blood, the greater chance you have for getting coronary heart disease.

LUMEN – The tube-like opening in arteries and other vessels that blood flows through on its journey throughout the body.

MAXIMUM HEART RATE – The number of beats per minute during rigorous exercise. It declines by about 25 to 30 percent between the ages 20 and 80, regardless of physical fitness status. Scientists estimate maximum heart rate by subtracting your age from 220.

MAXIMUM OXYGEN CONSUMPTION – The amount of oxygen used by the body at peak exercise capacity. Also known as VO2 max, it is considered the best measure of cardiorespiratory physical fitness. Women tend to have less lean muscle mass than men, and it is lean muscle mass that needs the most oxygen. When studies compare oxygen consumption based on the amount of lean muscle rather than overall body size, the gender differences disappear.Women, in other words, use the same amount of oxygen as men.

MEDIA – The middle layer of the arterial wall. It is composed of smooth muscle cells surrounded by a network of fibers primarily made of two proteins, collagen, and elastin. The elastin forms concentric rings within the vessel wall.

MITRAL VALVE – The valve between the left atrium and ventricle. It closes more slowly with age because the rate of blood flow into the left ventricle that pushes it closed decreases with age.

MYOCARDIUM – The heart muscle.

MYOCYTE – A heart muscle cell.Myocytes decline in number but grow larger with age.

NONINVASIVE TECHNIQUES – Medical procedures that do not require needle puncture, surgery, or entering the artery.

ORGANELLE – A structure inside a cell, such as the sarcoplasmic reticulum.

OXYGEN CONSUMPTION – The amount of oxygen the entire body uses in a certain time period. It is calculated by taking the amount of oxygen in the arteries and subtracting the amount left in the veins after the body’s cells have taken out oxygen. The result is then multiplied by cardiac output.

PRELOAD – The amount of blood in the left ventricle before contraction.

PROTEINS – Molecules composed of amino acids arranged in a specific order. Certain proteins, such as the calcium pump protein and the contractile protein myosin, appear to change with age which may account for some alterations in the function of the aging heart.

SARCOPLASMIC RETICULUM – A structure or organelle inside a myocyte. Its function is to store and release calcium for use during a contraction and to remove calcium after calcium transient causes a contraction. It removes calcium more slowly with age.

SINOATRIAL NODE – The heart’s pacemaker. A group of specialized cells in the right atrium wall that give rise to the electrical impulses that initiate contractions.

STROKE VOLUME – The amount of blood pumped with each heart beat.

SYSTOLE – The period during a heart beat when the heart muscle contracts and blood is pumped out.

VEINS – The blood vessels that return blood to the heart after the body’s cells have extracted oxygen.

VENTRICLE – A chamber of the heart that pumps blood out. The right ventricle pumps blood to the lungs where it picks up oxygen; the left ventricle pumps blood into the aorta, which distributes it to the rest of the body.

Acknowledgements

Writer
Doug Dollemore
Office of Communications and Public Liaison
National Institute on Aging
National Institutes of Health

Design
Megan Riordan, Designer
John Vance, Managing Art Director
Levine & Associates, Inc.
Washington, DC

Photography/Illustrations

“Anatomy of the Heart” illustration, Levine & Associates

Heart woodcut, courtesy of the National Library of Medicine, National Institutes of Health; MRI image, courtesy of Dynamic Graphics, Inc.

John Bicknell, illustration, Levine & Associates, photo courtesy of Doug Dollemore

John Bicknell photo, courtesy of Doug Dollemore

Edward Lakatta photo, courtesy of Edward Lakatta

“Heart Dynamics” illustration, Levine & Associates

Gary Gerstenblith photo, courtesy of Gary Gerstenblith

“In a Heart Beat” illustrations, Levine & Associates

PET/CT scan images of resting and stressed heart, courtesy of Swiss National Science Foundation, University Hospital, Zurich

“The Heart: Young and Old” illustration, Levine & Associates

Water aerobics photos, courtesy of the National Institute on Aging, National Institutes of Health

“When the Brain Talks to the Heart” illustration, Levine & Associates

Scientist at microscope, illustration, Levine & Associates, photo courtesy of Getty Images, Inc.

Myocyte, courtesy of Edward Lakatta

Calcium release in myocyte images, courtesy of the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia

“How a Myocyte Contracts” illustration, Levine & Associates

“Contractile Proteins” illustration, Levine & Associates

“Opposing Pressures” illustration, Levine & Associates

Christiaan Leewenburgh photo, courtesy of Christiaan Leewenburgh

Piero Anversa photo, courtesy of Piero Anversa

Stem cell, courtesy of Piero Anversa

Happy couple, illustration, Levine & Associates, photo courtesy of Getty Images, Inc.

Heart blood vessel photo, courtesy of the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia

Inflammation in the atherosclerosis process illustrations, courtesy of the Massachusetts Medical Society, The New England Journal of Medicine

“Age and Arteries” illustration, Levine & Associates

Magnified arterial wall section, courtesy of the University of Western Australia

Man getting blood pressure checked, courtesy of the National Institute on Aging, National Institutes of Health

“Production of Nitric Oxide” illustration, Levine & Associates

“Young and Old Arteries” illustration, Levine & Associates

DNA, courtesy of Getty Images, Inc.

C-reactive protein structure, adapted from original by Paul Ridker, Harvard University Medical School, Pathology Department

Endothelial cell, courtesy of Molecular Expressions: http://www.microscopy.fsu.edu, Florida State University

Exercise, courtesy of the National Institute on Aging, National Institutes of Health

Metabolic syndrome graph, Levine & Associates; Angelo Scuteri photo, courtesy of Angelo Scuteri

Man in kitchen, courtesy of Dynamic Graphics, Inc.

Crystallized cholesterol under the microscope, courtesy of Molecular Expressions: http://www.microscopy.fsu.edu, Florida State University

Nutrition label, courtesy of Getty Images, Inc.

Heart researchers, illustration, Levine & Associates, photos courtesy of Getty Images, Inc.

Willem Einthoven and early electrocardiograph, circa 1907, courtesy of the Heart Rhythm Foundation

Thanks to David Burton and Nancy Clark, JBS, Inc.
Special thanks to Edward G. Lakatta, M.D., chief of the Laboratory of Cardiovascular Science at the National Institute on Aging and to Jerome Fleg, M.D., medical officer at the National Heart, Lung and Blood Institute.