After I began researching this answer, I was hesitant to post my
answer, as answers that are contrary to what the customer expects are
sometimes not welcome. However, it appears the idea of free radicals
and their association with cell damage and aging is more than a fad
theory. There is a plethora of research proving it. Near the end of
the answer I posted a few articles that dispute it. Here is what I
As in many things scientific, one can often find studies
disproving previous studies. However, in this case, the free radicals
that are blamed for aging are oxygen-free radicals, known as reactive
oxygen species, or ROS. Oxygen, in the form our body uses, is in a
different form than the oxygen found in some free radicals.
?Oxygen is what is known as a free radical; it is highly unstable.
Oxygen is life saving but if you give 100% oxygen it is highly toxic.
Why does oxygen become toxic? It is a molecule which consists of two
atoms of oxygen, and when they are combined they balance each other
out. But it is unstable, and if the two atoms are separated, they
become two free radicals. But free radicals are not limited to oxygen.
Any molecule, any atom in the body can become a free radical, and when
it does it will try to balance itself by picking up an electron from
the neighbouring molecule which in turn becomes a free radical and the
vicious cycle continues until it is checked and controlled. If it is
not controlled, damage occurs in different parts of the body.?
?Free radicals are atoms or groups of atoms with an odd (unpaired)
number of electrons and can be formed when oxygen interacts with
certain molecules. Once formed these highly reactive radicals can
start a chain reaction, like dominoes. Their chief danger comes from
the damage they can do when they react with important cellular
components such as DNA, or the cell membrane. Cells may function
poorly or die if this occurs. To prevent free radical damage the body
has a defense system of antioxidants.?
It appears that free radicals have been proven to damage cells. Here?s one example:
?Researchers based at the University of Pennsylvania School of
Medicine have combined the precision of antibodies with the power of
an antioxidant enzyme to create a new way to protect transplanted
lungs from oxidative stress ? also known as free radical damage ?
before and during transplantation.?
?Free radicals can cause damage to parts of cells such as proteins,
DNA, and cell membranes by stealing their electrons through a process
called oxidation. (This is why free radical damage is also called
?oxidative damage.?) When free radicals oxidize important components
of the cell, those components lose their ability to function normally,
and the accumulation of such damage may cause the cell to die.
Numerous studies indicate that increased production of free radicals
causes or accelerates nerve cell injury and leads to disease.
Antioxidants , also known as ?free radical scavengers,? are compounds
that either reduce the formation of free radicals or react with and
neutralize them. Antioxidants often work by donating an electron to
the free radical before it can oxidize other cell components. Once the
electrons of the free radical are paired, the free radical is
stabilized and becomes non-toxic to cells. Therapy aimed at increasing
the availability of antioxidants in cells may be effective in
preventing or slowing the course of neurological diseases like HD.?
?It is a general principle of quantum chemistry that only two
electrons can exist in one bond. Specifically, each electron must have
opposite ?spin? from the other. Like male and female animals, ?up?
electrons pair up with ?down? electrons, and bonds are created. Paired
electrons are quite stable; nearly 100% of all electrons in the human
body exist in a paired state.
When a bond is broken (by radiation, for example), the electrons can
stay together (i.e., both go to one of the atoms and the other atom
gets none) or they can split up (one electron goes to each atom). If
they stay together, the molecular fragments are called ions, and they
are electrically charged (the atom with the electrons is negatively
charged and the one without the electrons is positively charged). A
good example of this is sodium chloride (salt) which splits up into a
chloride anion (Cl?) and a sodium cation (Na+).
If the electrons split up, the atoms are free radicals (molecules with
an unpaired electron). The unpaired electrons are highly energetic and
seek out other electrons with which to pair and stealing them in the
process. This electron ?rip off? is what makes free radicals both
useful and dangerous.
Since most electrons exist in a paired state, free radicals often end
up reacting with paired electrons. When they do so, one of the
electrons pairs with the (former) free radical and the ?odd electron
out? becomes another free radical (odd plus even equals odd). Only
when a free radical pairs up with another free radical is the free
radical terminated (odd plus odd equals even).
Antioxidants (also known as free radical scavengers) function by
offering easy electron targets for free radicals. In absorbing a free
radical, antioxidants ?trap? (de-energize or stabilize) the lone
free-radical electron and make it stable enough to be transported to
an enzyme which combines two stabilized free radicals together to
neutralize both. ??SWF?
?Chemical bonds are usually formed from the sharing of two
electrons, whereas a free radical is a species with one unpaired
electron. This makes many, but not all, free radicals chemically quite
reactive, as the species seek to find another electron to pair up
with. However, the definition includes common chemicals such as
oxygen. Not surprisingly, therefore, oxygen is a common reactant in
free-radical processes, having a propensity to take part in
single-electron transfer or free-radical addition reactions in which
electrons become paired. Another common gaseous chemical which is a
free radical is nitric oxide. It is now recognized to play a critical
role in vascular physiology, and with its molecular formula of NO,?
?In the present context, oxygen itself is one of the commonest
oxidizing agents. When oxygen acts as an oxidizing agent, it gains one
or more electrons from a substance. If it adds a single electron, the
superoxide free radical is formed (O2?- ). This is an extremely common
substance being produced in our bodies all the time: it has been
estimated that up to 2% of the oxygen used in mitochondrial
respiration could end up as superoxide, although the figure may be
less in healthy tissue. Thus oxygen is a common terminal electron
acceptor in biochemical processes. Superoxide radicals are also a key
feature of the phagocytic process (see below). Oxygen itself is a free
radical, but one with two unpaired electrons; reduction by adding one
electron to give superoxide involves the pairing of two of the
electron spins, leaving one unpaired. (Electron spin is a property
seemingly discovered by physicists to make chemistry more complicated,
although the property is put to good use in detecting free radicals,
just as nuclear spin is now widely used as the basis for magnetic
?The production of radical oxygen, the most common radical in
biological systems, occurs mostly within the mitochondria of a cell.
Mitochondria are small membrane-enclosed regions of a cell that
produce the chemicals a cell uses for energy. Mitochondria accomplish
this task through a mechanism called the "electron transport chain."
In this mechanism, electrons are passed between different molecules,
with each pass producing useful chemical energy. Oxygen occupies the
final position in the electron transport chain. Occasionally, the
passed electron incorrectly interacts with oxygen, producing oxygen in
?Whenever a free radical reacts with a non-radical, a chain
reaction is initiated until two free radicals react and then terminate
the propagation with a 2-electron bond (each radical contributing its
single unpaired electron). In biological systems free radicals have a
range of transitory existences depending upon their reactivity. Some
are stable, e.g. melanins can have a long lifetime, moderately stable
ones such as nitric oxide can have lifetimes of ~5 seconds and highly
unstable ones such as hydroxyl radicals exist for only a hundredth of
a microsecond. The free radicals of special interest in aging are the
oxygen free radicals. These free radicals often take an electron away
from a "target" molecule to pair with their single free electron. This
is called "oxidation". There are some closely related oxygen
containing molecules that are not strictly free radicals but
contribute to their production or are strong oxidants themselves, such
as singlet oxygen and hydrogen peroxide. The term "reactive oxygen
species" (ROS) is used to refer to these oxidants and the oxygen free
?Oxygen free radicals or ROS are implicated in many diseases including
neurodegenerative diseases (ALS, Parkinson's, Alzheimer's),
cataractogenesis, atherosclerosis, diabetes mellitus,
ischemia-reperfusion injury, kwashiorkor, certain toxicities, to
mention only a few, as well as in the aging process itself. This has
created the impression that all free radicals are highly damaging--in
short, all bad. A more informed examination of free radicals reveals a
range of unique functions in normal physiology and even in information
processing in the brain. Since free radicals can donate an electron to
an appropriate acceptor ("reduction reaction") or pair their unpaired
electron by taking one from an appropriate donor ("oxidation
reaction") they have major influences on the so-called "redox state"
in cells--important in normal regulatory reactions.?
?Evidence for free radical involvement in aging
The evidence for free radical/ROS involvement in aging is more
correlative than direct. However, there is increasing evidence for the
accumulation over time of damaged DNA and the modification of proteins
and other molecules. It is calculated that endogenously generated
oxygen free radicals make about 10,000 oxidative interactions with DNA
per human cell per day (Ames et al, 1993). These modifications and
damage to such vital molecules would be expected to ultimately lead to
deficiencies in normal functions in a global way--AGING. The least
contested, extensive animal studies on aging clearly demonstrate that
caloric restriction subtantially slows the rate of aging. Furthermore,
it delays the onset of age associated diseases. Weindruch (1996)
concludes that caloric restriction slows aging primarily by an
associated decrease in oxygen free radicals produced by the
?The body?s defense mechanisms against these free radicals are
referred to as antioxidants. When the amount of antioxidants in the
body is insufficient to do battle with the free radicals, these very
reactive molecules easily react with vital molecules in the body, such
as DNA, causing mutations (alterations) in the sequence of genetic
material. The accumulation of changes is then thought to lead to the
development of aging and degenerative diseases.
There are a number of reasons why the free radical theory has remained
popular and withstood the test of time.6 First, it provides many
plausible explanations for the process of aging. Second, there are a
growing number of studies that implicate free radical reactions in the
development of many chronic, age-related diseases (these will be
reviewed in part II of this series). Third, the free radical theory of
aging can easily be tested indirectly, using dietary experiments with
antioxidant supplements. Specific benefits of antioxidant supplements
in the prevention or treatment of age-related diseases will be
discussed in part III of this series. Fourth, the free radical theory
is the only one that encompasses all the concepts in almost all the
other theories of aging (except the neuroendocrine theory).
For instance, the free radical theory integrates all the theories
which pertain to metabolism and energy expenditure with the theories
dealing with molecular changes (mutations) at the DNA level. Thus, it
is easy to see how increasing the metabolic rate would generate an
explosion of free radicals or reactive oxygen species (ROS). The
reactive oxygen species would, in turn, react with DNA to cause
mutations which could lead to the development of disease?especially
?What are the major sources of free radical production (reactive
oxygen species or reactive nitrogen species) when we age? Oxidative
damage, particularly to proteins, has been widely postulated to be a
major causative factor in the loss of functional capacity during
senescence. It is hypothesized that as we age the defense mechanisms
preventing oxidation decline, and accelerated oxidative damage may,
therefore, trigger the deterioration in physiological function. Many
lines of evidence implicate, at least in part, oxidative damage to
proteins, lipids and nucleic acids as an important component of the
aging process. The main source of oxidant formation is believed to be
generated by the mitochondria, which could, therefore,play an
important role in the aging process.
The mitochondria's mainfunction is energy production. However, during
oxidative phosphorylation, highly reactive oxygen radicals are
generated and subsequently attack cellular components such as
respiratory chain proteins and mitochondrial DNA. It has been
estimated that the release of reactive intermediate accounts for 2-5%
of the oxygen consumed during respiration. Mutations in mitochondrial
DNA can lead to the production of less functional respiratory chain
proteins, resulting in an increased free radical production and
possibly more mitochondrial DNA mutations. This phenomenon is often
referred to as the mitochondrial theory of aging, which may lead to
random accumulation of mitochondrial DNA mutations. This could
ultimately reduce energy output and contribute to the common signs of
normal aging. We, therefore, closely investigate the oxidants
generated by the mitochondria, energy production, and the antioxidant
defenses in the mitochondria.?
?Normally, bonds don?t split in a way that leaves a molecule with
an odd, unpaired electron. But when weak bonds split, free radicals
are formed. Free radicals are very unstable and react quickly with
other compounds, trying to capture the needed electron to gain
stability. Generally, free radicals attack the nearest stable
molecule, "stealing" its electron. When the "attacked" molecule loses
its electron, it becomes a free radical itself, beginning a chain
reaction. Once the process is started, it can cascade, finally
resulting in the disruption of a living cell.
Some free radicals arise normally during metabolism. Sometimes the
body?s immune system?s cells purposefully create them to neutralize
viruses and bacteria. However, environmental factors such as
pollution, radiation, cigarette smoke and herbicides can also spawn
Normally, the body can handle free radicals, but if antioxidants are
unavailable, or if the free-radical production becomes excessive,
damage can occur. Of particular importance is that free radical damage
accumulates with age.?
?The mitochondrial respiratory chain plays a key role in the cell.
It is responsible for the conversion of oxygen to two molecules of
water. This direct reduction reaction involving four electrons is made
possible by a complex system of proteins and enzymes (cytochromes)
located in the inner membrane of the mitochondrion. The consequences
of this mitochondrial activity are dual and paradoxical. On the one
hand, the mitochondrion provides the cell with an important source of
energy, since oxygen reduction generates 36 molecules of adenosine
triphosphate, a high-energy compound. On the other hand, about 0.4 to
4% of the oxygen is not correctly converted to water, because of
electron leakage resulting from imperfections in the respiratory
chain. By reduction involving a single electron, oxygen gives rise to
activated oxygen species (AOS), among which are free radicals such as
the superoxide anion or the hydroxyl radical. In chemistry, a free
radical is an atom or a molecule whose chemical structure is
characterised by the presence of an unpaired electron that makes this
chemical species much more reactive than the atom or molecule from
which it derives. Other, non-radical oxygen-containing entities can
also be produced, such as hydrogen peroxide (H2O2) or singlet oxygen
(1O2). The formation of AOS requires the presence of transition metals
such as iron or copper, acting as necessary catalysers throughout the
chemistry of free radicals?
Eating fruits and veggies can reduce cell levels of oxidised DNA.
Oxidized DNA is blamed for it?s role in causing cancer.
?Oxygen free radicals produced endogenously and via the action of
pro-inflammatory cytokines play a major role in ? cell destruction in
type I diabetes as well as following islet cell transplantation, as
depicted in the model below.?
?An example is Fenton's reaction, the reduction of peroxide to
water and hydroxyl radical by ferrous iron. Hydroxyl radical is one of
the most powerful oxidizing agents known. Simply put, reducing agents
act as prooxidants by reducing nonradical forms of oxygen to radical
forms, usually with heavy atom involvement. Similarly, they can act as
antioxidants by reducing radical forms of oxygen, by terminating
radical chain reactions, or by, for example, reducing hydroperoxides.
This dual property can be of great significance. For example, in
humans uric acid is probably the primary extracellular antioxidant. On
the other hand, a Fenton-type reaction of phagocytized urate with
granulocyte-produced peroxide may contribute to the etiology of gout.?
?Chemical antioxidants act by donating an electron to a free radical
and converting it to a nonradical form. Likewise, such reducing
compounds can terminate radical chain reactions and reduce
hydroperoxides and epoxides to less reactive derivatives. However,
chemical antioxidant defense is a double-edged sword. When an
antioxidant scavenges a free radical, its own free radical is formed.
Many antioxidants can act as pro-oxidants by, for example, reducing
nonradical forms of oxygen to their radical derivatives, particularly
if redox cycling occurs. The exact mix of pro- and antioxidant
properties of a reducing compound is a complex interaction involving
pH, relative reactivities of radical derivatives, availability of
metal catalysts, and so forth. For example, the anti- or pro-oxidant
properties of sulfhydryl compounds depend upon pH (29-31), those of
beta carotene upon oxygen concentration (69). Likewise, uric acid,
probably a significant antioxidant in higher primates (32-36)
participates in a Fenton-type reaction with peroxide(35, a property
which may be important in the etiology of gouty inflammatory disease.?
?For many years the existence of free radicals in biological
systems was dismissed as either non-existent or simply an unimportant
curiosity. However, more recently due to improved investigational
techniques, this view has changed rather dramatically. Currently, free
radicals have found a place in the aetiology of many diseases and
there is a great deal of enthusiasm regarding the role of free
radicals in many previously unexplained disease phenomena. To name a
few important areas; free radicals have found a role in the rheumatoid
arthritis, Alzheimer's disease, hypertension, myocardial ischemia,
liver cell injury and carcinogenesis. The reason as to why the role of
free radicals has been so ambiguous is probably due to their
ultra-short half-life. However, free radicals have finally come into
existence through the use of more sophisticated methods of assay.?
?The fact that they are highly reactive means that they have low
chemical specificity; i.e. they can react with most molecules in its
vicinity. This includes proteins, lipids, carbohydrates and DNA. It
also means that in trying to gain stability by capturing the needed
electron they don't survive in their original state for very long and
quickly react with their surroundings. Hence, free radicals attack the
nearest stable molecule, "stealing" its electron. When the "attacked"
molecule loses its electron, it becomes a free radical itself,
beginning a chain reaction. Once the process is started, it can
cascade, finally resulting in the disruption of a living cell.?
Further Information on Free Radicals and Disease
?In results that counter the idea that oxygen free radicals cause
aging, an MIT researcher reports in the July 18 issue of Nature that
calorie restriction prolongs life because it increases respiration,
not because it decreases oxygen free radicals.
MIT biologist Leonard Guarente believes "the conventional wisdom on
oxygen radicals is dead wrong. Our results (in yeast) are contrary to
the frequent suggestion that calorie restriction functions by slowing
metabolism and thereby slowing the generation of free radicals."
Guarente, who is working on a book on aging to be published this fall,
discovered in 2000 that calorie restriction activates the silenced
information regulator (SIR2) gene, which has the apparent ability to
slow aging. This gene makes a protein called Sir2, which Guarente has
shown is integrally tied to extending life span in yeast and in the
roundworm. Humans carry a similar gene.?
?There is no doubt that routine metabolic chemistry in each cell
produces legions of free-radicals every hour, in the process of "just
living." And there is no doubt that exposure to ionizing radiation
produces some extra free-radicals in irradiated cells. And so
radiation scientists such as Dr. Daniel Billen (1990) have tried to
argue that low-doses of ionizing radiation must be inconsequential
because they add so few free-radicals to a cell, by comparison with
the number of free-radicals naturally in each cell anyway.
1c The hidden (and false) assumptions in such reasoning
are (1) that the nature of damage done by ionizing radiation is the
same as the nature of damage done by routine metabolic free-radicals,
and (2) that damage therefore can be compared by comparing the
relative numbers of free-radicals. The erroneous "same-nature"
assumption is at the heart of the Free-Radical Refrain, and has been
disseminated by statements like "We are irradiating ourselves by
living" (Dr. Bruce Ames 1994, p.18; Ames 1995, p.5259).
1d Using numbers from Dr. Billen's own presentation, plus
a reality-check with actual observations, we can demonstrate that the
nature of damage from ionizing radiation cannot possibly be the same
as the nature of the damage from routine metabolic free-radicals. We
have not seen this demonstration elsewhere, but perhaps someone else
has put it forth, too. We use nothing but simple multiplication and
division (Part 3).?
I?m afraid I found very little online about debunking the idea of
free radicals causing cell damage and aging. Please read each site
for complete information. Copyright restrictions prevent me from
posting more than I have. Also, please note that I omitted any
information found on junk science sites, or sites that sell products
such as antioxidants and supplements, and used reliable sites.
I hope this information has helped you. It certainly appears that free
radicals do cause cell damage, disease, and aging. If anything is
unclear, please request an Answer Clarification, and allow me to
respond, before you rate.
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