Denham Harman
Encyclopedia
Denham Harman MD, PhD, FACP, FAAA biogerontologist is Professor emeritus
at the University of Nebraska Medical Center
. Harman is widely known as the "father of the free radical theory of aging".
and his M.D. from Stanford University
, finishing his internship in 1954.
Immediately after earning his Ph.D., in 1943, Harman joined the reaction kinetics
department of Shell Oil in Emeryville, California
. He worked for six years as a Shell research chemist
, in part studying free radical reactions
in petroleum products. During that period he was granted 35 patent
s, one for a compound used in plastic strips to kill flies
("Shell No Pest Strip").
Harman became fascinated with the phenomenon of aging
, its cause and possible cure. To assist him in understanding this problem he went to medical school at Stanford University. Harman became chair
of cardiovascular research at the University of Nebraska College of Medicine
in 1958.
Harman has been married to the same woman for most of his life, a journalism
student who he met at a fraternity
dance while at the University of California. The couple has four children and four grandchildren. Harman maintained a healthy lifestyle throughout his life. He has never smoked
and drinks alcohol
in moderation. He ran two miles a day until he was 82. He quit because of a back injury, but he continued to take regular walks to help him maintain a weight of 140 pounds on his 5-foot-10 frame.
and residency
in internal medicine
, Harman became a research associate at the Donner Laboratory of Medical Physics
at UC Berkeley
, where he was able to pursue the puzzle of the cause of aging
. After four months of frustration he hit upon the idea of free radicals
as cause of the damage to macromolecules known as "aging
". Although other scientists were reluctant to accept his theory he was finally able to get it published in what is now a much-cited article in the Journal of Gerontology.
Harman attempted to detect free radicals in association with the enzyme
catalase
, but without success. He attempted to do life span
studies with short-lived strains of mice
subject to radiation
and given the radiation protection compound 2-MEA (2-mercaptoethylamine
), and was able to show a 30% increase in average life expectancy
. He was able to show extension of life expectancy with a number of antioxidant
s.
In 1961, Harman published a study showing that the degree of polyunsaturation in fats had a dramatic effect on cancer
rates in mice. The most highly polyunsaturated dietary fats
were found to be the most carcinogen
ic.
In 1968 Harman published a dietary antioxidant study showing that the food preservative BHT
fed over a lifetime to mice produced a 45% increase in life span. Harman became concerned that although many of his studies showed an increase in average lifespan
by antioxidants, none showed an increase in maximum life span
.
After years of frustration over his inability to increase maximum lifespan with antioxidant supplements, Harman came to the conclusion that mitochondria were producing as well as being damaged by free radicals, but that exogenous
antioxidants don't enter the mitochondria. And that it is mitochondria that determine lifespan. He published his ideas on what he called the "Mitochondrial Theory of Aging" in the April 1972 issue of the Journal of the American Geriatrics Society.
were studying the biological
aspects of aging
, and fewer still had a serious interest in discovering the cause of aging. In 1970 he became a founder of the American Aging Association
(AGE) to create a society of scientists focused on aging research and advocacy of aging research. In 1985 he became a founder of the International Association of Biomedical Gerontology (IABG).
Emeritus
Emeritus is a post-positive adjective that is used to designate a retired professor, bishop, or other professional or as a title. The female equivalent emerita is also sometimes used.-History:...
at the University of Nebraska Medical Center
University of Nebraska Medical Center
The University of Nebraska Medical Center is a public academic health sciences center located on 42nd and Emile Streets in Midtown Omaha, Nebraska. UNMC is the only public academic health science center in Nebraska.-Academics and rankings:...
. Harman is widely known as the "father of the free radical theory of aging".
Background
Harman earned his BS and Ph.D. in 1943 from the College of Chemistry at the University of California, BerkeleyUniversity of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...
and his M.D. from Stanford University
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
, finishing his internship in 1954.
Immediately after earning his Ph.D., in 1943, Harman joined the reaction kinetics
Chemical kinetics
Chemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...
department of Shell Oil in Emeryville, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
. He worked for six years as a Shell research chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
, in part studying free radical reactions
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
in petroleum products. During that period he was granted 35 patent
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
s, one for a compound used in plastic strips to kill flies
Fly
True flies are insects of the order Diptera . They possess a pair of wings on the mesothorax and a pair of halteres, derived from the hind wings, on the metathorax...
("Shell No Pest Strip").
Harman became fascinated with the phenomenon of aging
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...
, its cause and possible cure. To assist him in understanding this problem he went to medical school at Stanford University. Harman became chair
Chair (official)
The chairman is the highest officer of an organized group such as a board, committee, or deliberative assembly. The person holding the office is typically elected or appointed by the members of the group. The chairman presides over meetings of the assembled group and conducts its business in an...
of cardiovascular research at the University of Nebraska College of Medicine
University of Nebraska Medical Center
The University of Nebraska Medical Center is a public academic health sciences center located on 42nd and Emile Streets in Midtown Omaha, Nebraska. UNMC is the only public academic health science center in Nebraska.-Academics and rankings:...
in 1958.
Harman has been married to the same woman for most of his life, a journalism
Journalism
Journalism is the practice of investigation and reporting of events, issues and trends to a broad audience in a timely fashion. Though there are many variations of journalism, the ideal is to inform the intended audience. Along with covering organizations and institutions such as government and...
student who he met at a fraternity
Fraternities and sororities
Fraternities and sororities are fraternal social organizations for undergraduate students. In Latin, the term refers mainly to such organizations at colleges and universities in the United States, although it is also applied to analogous European groups also known as corporations...
dance while at the University of California. The couple has four children and four grandchildren. Harman maintained a healthy lifestyle throughout his life. He has never smoked
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
and drinks alcohol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
in moderation. He ran two miles a day until he was 82. He quit because of a back injury, but he continued to take regular walks to help him maintain a weight of 140 pounds on his 5-foot-10 frame.
Development of the Free Radical Theory of Aging
In 1954, between his internshipMedical intern
A medical intern is a term used in the United States for a physician in training who has completed medical school. An intern has a medical degree, but does not have a full license to practice medicine unsupervised...
and residency
Residency (medicine)
Residency is a stage of graduate medical training. A resident physician or resident is a person who has received a medical degree , Podiatric degree , Dental Degree and who practices...
in internal medicine
Internal medicine
Internal medicine is the medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases. Physicians specializing in internal medicine are called internists. They are especially skilled in the management of patients who have undifferentiated or multi-system disease processes...
, Harman became a research associate at the Donner Laboratory of Medical Physics
Medical physics
Medical physics is the application of physics to medicine. It generally concerns physics as applied to medical imaging and radiotherapy, although a medical physicist may also work in many other areas of healthcare...
at UC Berkeley
University of California
The University of California is a public university system in the U.S. state of California. Under the California Master Plan for Higher Education, the University of California is a part of the state's three-tier public higher education system, which also includes the California State University...
, where he was able to pursue the puzzle of the cause of aging
Senescence
Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...
. After four months of frustration he hit upon the idea of free radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
as cause of the damage to macromolecules known as "aging
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...
". Although other scientists were reluctant to accept his theory he was finally able to get it published in what is now a much-cited article in the Journal of Gerontology.
Harman attempted to detect free radicals in association with the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
, but without success. He attempted to do life span
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
studies with short-lived strains of mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
subject to radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
and given the radiation protection compound 2-MEA (2-mercaptoethylamine
Cysteamine
Cysteamine is the chemical compound with the formula HSCH2CH2NH2. It is the simplest stable aminothiol and a degradation product of the amino acid cysteine. It is often used as the hydrochloride salt, HSCH2CH2NH3Cl....
), and was able to show a 30% increase in average life expectancy
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
. He was able to show extension of life expectancy with a number of antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s.
In 1961, Harman published a study showing that the degree of polyunsaturation in fats had a dramatic effect on cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
rates in mice. The most highly polyunsaturated dietary fats
Unsaturated fat
An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fat molecule is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond. Where double bonds are formed, hydrogen atoms are...
were found to be the most carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
ic.
In 1968 Harman published a dietary antioxidant study showing that the food preservative BHT
Butylated hydroxytoluene
Butylated hydroxytoluene , also known as butylhydroxytoluene, is a lipophilic organic compound that is primarily used as an antioxidant food additive as well as an antioxidant additive in cosmetics, pharmaceuticals, jet fuels, rubber, petroleum products, electrical transformer oil, and embalming...
fed over a lifetime to mice produced a 45% increase in life span. Harman became concerned that although many of his studies showed an increase in average lifespan
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
by antioxidants, none showed an increase in maximum life span
Maximum life span
Maximum life span is a measure of the maximum amount of time one or more members of a population has been observed to survive between birth and death.Most living species have at least one upper limit on the number of times cells can divide...
.
After years of frustration over his inability to increase maximum lifespan with antioxidant supplements, Harman came to the conclusion that mitochondria were producing as well as being damaged by free radicals, but that exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
antioxidants don't enter the mitochondria. And that it is mitochondria that determine lifespan. He published his ideas on what he called the "Mitochondrial Theory of Aging" in the April 1972 issue of the Journal of the American Geriatrics Society.
Organizational Accomplishments
In 1969 Harman became concerned that few of those involved in gerontologyGerontology
Gerontology is the study of the social, psychological and biological aspects of aging...
were studying the biological
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
aspects of aging
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...
, and fewer still had a serious interest in discovering the cause of aging. In 1970 he became a founder of the American Aging Association
American Aging Association
The American Aging Association is a non-profit, tax-exempt biogerontology organization of scientists and laypeople dedicated to biomedical aging studies intended to slow the aging process. The abbreviation AGE is intended to be representative of the organization, even though it is not an acronym...
(AGE) to create a society of scientists focused on aging research and advocacy of aging research. In 1985 he became a founder of the International Association of Biomedical Gerontology (IABG).