STUDENT PROJECT

OXIDATIVE STRESS AND AGING

SGD B7
Nareswari Pawestri 1902511135
Dwina Hotdiva Debataraja 1902511136
Jonathan Edmund Harianto 1902511137
Anastasia Vania Trixie Kustianto 1902511138
Ayuni Putri Adhini 1902511141
Shanty Dewi 1902511142
Putu Andrea Wisnu Sebastian 1902511143
Aizar Veza Prasetyo 1902511144
Daffa Satria Ananda 1902511146
Giovanca Verentzia Purnama 1902511148
Wilson Halim 1902511149
Yohana Reena Bunyamin 1902511150
Anak Agung Bagus Putra Indrakusuma 1902511151

PROGRAM STUDI SARJANA KEDOKTERAN

DAN PROFESI DOKTER
FAKULTAS KEDOKTERAN
UNIVERSITAS UDAYANA
DENPASAR 2019
 FOREWORD

Praise the presence of The Almighty God for all the abundance and grace, we
can complete the preparation of the Student Project entitled "Oxidative Stress and
Aging" on time. For that reason, the authors thank all the team members who have
worked well in completing this work and for those who help this project.
We are also fully aware that this work is not free from deficiencies and errors.
Therefore, we apologize profusely and hope the reader to provide constructive input
for the perfection of this work going forward. Hopefully this work can provide
information for readers and be useful for the development of insight and
improvement of knowledge for all of us.

Denpasar, 29th October 2019

Writer team

ii
 TABLE OF CONTENTS

Cover Page .......................................................................................................... i

Foreword ............................................................................................................. ii
Table of Content .................................................................................................. iii
Figure List ........................................................................................................... iv
CHAPTER I INTRODUCTION
1.1 Background ................................................................................................... 1
1.2 Research questions ........................................................................................ 2
1.3 Purpose of the Research ................................................................................ 2
1.4 Benefit of the Research ................................................................................. 3
CHAPTER II CONTENT
2.1 Oxidative Stress ........................................................................................... 4
2.2 Aging ............................................................................................................. 10
2.3 The Effect of Oxidative Stress on Aging ...................................................... 12
2.4 The Prevention of Oxidative Stress and Aging ............................................. 14
CHAPTER III SUMMARY
3.1 Conclusion .................................................................................................... 16
REFERENCES .................................................................................................. 17

iii
 FIGURE LIST

Figure 1.1 Benign skin tumors ............................................................................ 1

Figure 2.1 Factor of aging ................................................................................... 11
Figure 2.2 Sun radiation ...................................................................................... 13

iv
 CHAPTER I
INTRODUCTION

1.1 Background
Aging become one of the main problem of people nowadays. Many
people try to prevent aging. Aging could be the biggest problem for people who
maintain their appearance. Aging is a change in human body that happen
because of the oxygen reactivity.1 Aging could cause DNA damage and
fragmentation, and it causes apoptosis (programmed cell death) also produce a
visibly older looking face.1 Aging that occurs will accumulate over time to
cause significant physiological, psychological, and social changes.1 Aging also
can cause cellular responses disrupted.1
The main cause of aging is free radicals and reactive oxygen species
(ROS).2 Free radicals themselves are produced by our body every day as a result
of cell metabolism.2 If the level of free radicals exceeds the limit of antioxidant
defenses, oxidative stress will occur.2 Oxidative stress will cause aging which
will have an impact on someone’s appearance. Aging makes someone look
much older than their actual age. This could be dangerous, because appearance
become one of the most important things to people nowadays.

Figure 1.1 Benign skin tumors

Source: Jurnal Generasi Kampus
Aging can cause skin aging and the appearance of wrinkles.2 This wrinkle
causes a person look older than their actual age. Besides wrinkles, aging also

1
 2

causes the skin to lose its moisture so the skin tends to have dry texture. 2 Dry
skin will cause irritating itching.2 Benign skin tumors can also occur due to
excessive oxidative stress.2 This benign tumor will disturb our appearance
because of its shape in the form of bulges with red to brownish black.2
Besides causing appearance problems, aging can also cause muscle
fatigue because oxidative stress reduces muscle endurance during physical
activity.3 This condition must be avoided, especially for athletes. Oxidative
stress causes a person cannot do physical activity with maximum energy. Even
ordinary people will have difficulty carrying out daily physical activities. Aging
also causes oxygen consumption increase sharply 10-15 times the normal rate
when doing physical activities.3
Because the problem of aging due to oxidative stress is very much
experienced and becomes a common problem, our group wants to make a study
of aging and oxidative stress. In this study we will discuss what is the meaning
of oxidative stress and aging. We will also describe about the relation between
aging and oxidative stress. We will also describe about how to prevent oxidative
stress and reduce aging.

1.2 Research questions

1. What is oxidative stress?
2. What is aging?
3. How does oxidative stress correlate with aging?
4. How to prevent oxidative and stress aging?

1.3 Purpose of the Research

The purpose of this research is:
1. To introduce oxidative stress generally
2. To develop a deeper understanding of aging
3. To understand the impact oxidative stress has on aging
4. To develop understanding of the oxidative stress and aging prevention
 3

1.4 Benefit of the Research

As people nowadays strives for everlasting beauty, understanding the
information behind the secret to beauty really helps. In general, studying
oxidative stress and aging benefitted the public. Through this study, one would
have a deeper understanding of the oxidative stress and aging. One would know
how to maintain a healthy and fresh look and this will lead them to search and
conduct even a deeper and more complex research about the oxidative stress
and aging.
 CHAPTER II
CONTENT

2.1 Oxidative Stress

2.1.1 Definition of Oxidative Stress
Oxidative stress is a condition when free radicals and the stabilizing
agent’s antioxidant enzymes in the body are imbalance.4 The main factor of
oxidative stress are lack of antioxidants or excess free radicals production.
Other definition of oxidative stress is a condition where the level of Reactive
Oxygen Species (ROS) increase – In normal quantities, ROS have some
physiology functions such as for protection, hormone biosynthesis,
fertilization, and cellular signal. Oxidative stress causes successive damage
from body’s cells to higher level of the body, for example: the basis of
pathogenesis of chronic diseases such as cardiovascular, autoimmune,
pulmonary, metabolic disorders, and aging.5

2.1.2 Etiology of Oxidative Stress

In aerobic metabolic process, produce 2.5% (3.4 kg/24) ROS from the
total need of oxygen.6 ROS are unpaired molecules so that very reactive and
unstable. ROS can stand only for milliseconds before they react with other
molecules to make them stable.6 The most dangerous and destructive are
superoxide, hydroxyl, and perhydroxyl, these molecules will attack body’s
cells and cause oxidative stress.6 Some tissues will be damaged by ROS, for
example DNA, lipid, and protein. The antibody also will react from the
normal tissue and this is the beginning of autoimmune disorder.6 ROS
interaction with DNA will change the chemical structure of DNA and causing
mutation. ROS reaction to lipid and plasma lipoproteins cause the formation
of lipid peroxide which can modify the protein and nucleid acid base so that
the protein is no longer known as their own by the immune system (considered
as a foreign cell). Modification between protein and lipoprotein (LDL) make
the liver’s LDL not recognizing themselves so that the liver can not clean

4
 5

them up, then macrophage will catch the LDL and make the macrophage
bigger so the blood vessels will be clogged up – causing the cholesterol.6

2.1.3 Risk Factor of Oxidative Stress

The simple free radicals that can be found in our environment are ozone,
certain pesticides and cleaners, cigarette or smoke, radiation, pollution, a diet
high in sugar, fat, and alcohol. High intensity of exercise can cause stress
oxidative because of the oxygen volume which enter the body.5

2.1.4 Pathophysiology of Oxidative Stress

Free radicals are atoms or molecules that highly reactive and
unstabilized because of having unpaired electron in their outer orbital. These
molecules can be formed when oxygen oxidizes with certain molecules.
These radicals produced in cells by losing or accepting a single electron, as
oxidants or reductants. A cell or a tissue can be damaged by lipid peroxidation
and even mutated when free radicals oxidize DNA in cell and eventually
cause cancer.
Reactive oxygen species (ROS) are produced by living organisms in
normal cellular metabolism. ROS function in physiological cell processes at
low and moderate concentrations, but at high concentrations, they modificate
cell components, such as lipids, proteins, and DNA. ROS plays an important
role in aging and in age-related diseases. Aerobic organisms have integrated
antioxidant systems, which include enzymatic and nonenzymatic antioxidants
that effective in blocking harmful effects of ROS. However, in pathological
conditions, the antioxidant systems can be overwhelmed7. There are
endogenous and exogenous sources of ROS:
1. Endogenous Source
ROS are produced from molecular oxygen in normal cellular
metabolism. The 3 major ROS that are of physiological significance are
superoxide anion (O2-.), hydroxyl radical (●OH), and hydrogen peroxide
(H2O2).
 6

Superoxide anion is formed by the addition of 1 electron to the

molecular oxygen. This process is mediated by nicotine adenine
dinucleotide phosphate [NAD(P)H] oxidase or by mitochondrial electron
transport system. Normally, electrons are transferred through
mitochondrial electron transport chain for reduction of oxygen to water,
but approximately 1% to 3% of all electrons leak from the system and
produce superoxide. NAD(P)H oxidase can be found in leukocytes,
monocytes, and macrophages. These cells produce a burst of superoxide
in phagocytosis. Superoxide is converted into hydrogen peroxide by
superoxide dismutase enzyme. Hydrogen peroxide is also produced by
xanthine oxidase, amino acid oxidase, and NAD(P)H oxidase.
In a reactions called Haber-Weiss and Fenton reactions, H2O2 that
react with Fe2+ or Cu2+ can breakdown to hydroxyl (OH-). O2- that react
with H2O2 also generate OH-. Hydroxyl radical is the most reactive of
ROS and can damage proteins, lipids, and DNA. For example, it can
\start lipid peroxidation by taking an electron from polyunsaturated fatty
acids.
The reactivity of H2O2 is expanded via eosinophil peroxidase and
myeloperoxidase (MPO). In activated neutrophils, H2O2 is consumed by
MPO. With chloride ion, H2O2 is converted to hypochlorous acid
(HOCl). HOCl is highly oxidative and has function in killing of the
pathogens in the airways.
Other oxygen-derived free radicals are the peroxyl radicals
(ROO••). Simplest form of these radicals is hydroperoxyl radical
(HOO••) and has a role in fatty acid peroxidation. Free radicals can
trigger lipid peroxidation chain reactions. Lipid peroxidation chain
reaction is happen when ROS take an electron from lipid in cell
membrane, which leaves that lipid with an unpaired electron itself. That
lipid do the same thing to another lipid and it can propagate this process
in sort of chain reaction. Peroxidation of lipids can damage the cell
membranes and leads to rearrangement of membrane structure.
 7

2. Exogenous Sources
a. Cigarette Smoke
Cigarette smoke contains many free radicals. In addition, inhalation
of cigarette smoke into the lung also activates some endogenous
mechanisms, such as accumulation of neutrophils and macrophages,
which further increase the oxidant injury.
b. Ozone Exposure
Ozone exposure can cause lipid peroxidation and induce influx of
neutrophils into the airway epithelium. Exposure to ozone also causes
the release of inflammatory mediators, such as MPO, eosinophil
cationic proteins and also lactate dehydrogenase and albumin.
c. Hyperoxia
Hyperoxia is a condition of higher oxygen levels than normal partial
pressure of oxygen in the lungs or other body tissues. It leads to
greater production of reactive oxygen.
d. Ionizing Radiation
Ionizing radiation converts hydroxyl radical, superoxide, and organic
radicals to hydrogen peroxide and organic hydro peroxides. These
hydro peroxide species react with redox active metal ions, such as Fe
and Cu and induce oxidative stress.
e. Heavy Metal Ions
Heavy metal ions, such as iron, copper, cadmium, mercury, nickel,
lead, and arsenic, can induce generation of reactive radicals and cause
cellular damage via depletion of enzyme activities through lipid
peroxidation and reaction with nuclear proteins and DNA.
One of the most important mechanisms of metal-mediated free
radical generation is via a Fenton-type reaction. Superoxide ion and
hydrogen peroxide can interact with transition metals, such as iron
and copper, via the metal catalyzed Haber-Weiss/Fenton reaction to
form OH radicals8.
 8

Antioxidant defense protects biological systems from free

radical toxicity and includes both endogenous and exogenous
molecules.
1) Endogenous antioxidants include enzymatic and non-enzymatic
pathways.
2) The primary antioxidant enzymes are superoxide dismutase
(SOD), catalase (CAT), and glutathione peroxidase (GSH-Px).
SOD takes care of superoxide, catalase takes hydrogen peroxide,
and GSH-Px for hydroxyl radical.
3) The non-enzymatic antioxidants are molecules that terminate the
free radical chain reactions: bilirubin, α-tocopherol (vitamin E),
and β-carotene are present in blood while in plasma, albumin and
uric acid account for 85% of antioxidant capacity.
4) Exogenous antioxidants include ascorbic acid (vitamin C), which
scavenges hydroxyl and superoxide radical anion, α-tocopherol
(vitamin E), that against lipid peroxidation of cell membranes,
and phenolic antioxidants, which include stilbene derivatives oil
lecitinas, selenium, zinc, and drugs such as acetylcysteine.
Oxidative stress occurs when there is an imbalance between the
formation and the removal of ROS because of an overproduction
and/or an impaired ability to neutralize them or to repair the
resulting damage7.

2.1.5 Phatogenesis of Oxidative Stress

1. Cancer
Cancer as human health problem cause is create trough a complex
process. Oxidative DNA damage one of coding protein which result in
cancer development. DNA oxidation mostly produce hydrolyzed DNA
as a product, it is considered as a relevant carcinogenic chemical. Not
only that, but Oxidation stress also tribute to the DNA damage that cause
the tumor onset.
 9

2. Cardiovascular Disease
This disease has a multifactorial etiology, but since last year oxidative
stress considered as a primary or a secondary cause of many CVD.
Oxidative stress stimulates the atherosclerosis with atheromatous plaque
which result in early endothelial inflammation that leads to Reactive
Oxygen Species (ROS) formation by the macrophages. Its oxidized the
low-density lipoprotein and cause the formation of foam cell and lipid
accumulation.
3. Neurological disease
Oxidative stress itself already known being responsible for the cause of
several neural disease such as Alzheimer’s disease (AD), amyotrophic
lateral sclerosis, depression, and memory loss. Oxidative stress damage
neuron and cause the progression to dementia example - amyloid, a
toxic peptide in brain which produced by neurodegeneration observed.
4. Respiratory
In respiratory oxidative stress also provide several disease such as asthma
and chronic obstructive pulmonary disease (COPD)
5. Rheumatoid Arthritis
It is a chronic inflammatory disorder that affect the joints and
surrounding tissue.it cause by the T cell infiltration that initiate and
progress by the free radical that can be seen by the increase of isoprostane
6. Kidney disease
Oxidative stress involved in large amount area of renal apparatus such as
glomerulus and nephritis of interstitial tubule, renal failure, proteinuria
and uraemia. Reactive oxygen Species production persuade the
recruitment of the inflammatory cell and proinflammatory cytokine and
cause the kidney negatively affected. Certain drugs such as cyclosporine,
tacrolimus, gentamycin dan bleomycin are known to be nephrotoxic and
increase the free radical levels and oxidation stress by lipid peroxidation.8
 10

7. Sexual maturation
Oxidative stress are founded to be responsible for a delayed sexual
maturation and puberty. It can be seen by exposing children or pregnant
in pubertal age to the cd.9

2.2 Aging
2.2.1 Definition of Aging
According to the U.S. Department of Health & Human Services, aging
is associated with changes in dynamic biological, environmental,
physiological, behavioral, psychological, and social processes. The changes
are sometimes benign, such as having wrinkles, but some can cause the
muscles capability to decline, processing information, the increased
susceptibility of disease, frailty, or even disability.10
Aging is a result from the impact of the accumulation of a wide variety
of cellular and molecular damage. These changes are neither consistent nor
linear and they are only slightly associated with someone’s age in years.
While some 65 year-olds enjoy a wonderful life with an amazing health
conditions, some 65 year-olds are frail and require help from other people.11
Besides biological changes, ageing is also associated with other life
transitions such as moving to a different place, retirement, and the death of a
loved one. When developing a public health response to aging, it is important
to not just consider approaches that improve the losses associated with older
age, but also those that may reinforce recovery, psychosocial growth, and
adaptation.11

2.2.2 Factors of Aging

Aging can occur because a lot of factors. The factors are divided into
two types, environmental and genetical. For example, cells that are exposed
to a harmful environment will cause a mutation. The mutation will damage
DNA of the cell. Harmful environmental exposure can shorten the telomere,
DNA-Protein complexes that cap the ends of linear DNA Strands, stabilizing
 11

and preventing chromosome instability12. Shortening of the telomeres can

cause cell’s apoptosis, the death of cell.
Progeroid syndrome is an example of aging which is caused by genetic
factor. Progeria or progeroid syndrome is a genetical disease which causes
hair loss, short stature, skin tightness, cardiovascular diseases and
osteoporosis13. Progeria is a disease which accelerates aging. This condition
appears because of gen mutation in the body. Accelerated aging can cause a
lot of disease, such as cancer and even death. Mutation can cause the growth
of cancer cells. Oxidative stress, imbalance between antioxidants and free
radicals, can also contribute to cause aging.

Figure 2.1 Factor of aging

Source: stemcureformula.com
Free radicals can arise from metabolism in the human body or from
external factors such as X-rays, ozone, cigarette smoke, air pollution, and
factory chemical waste. Free radicals will continue to appear in cells as waste
from enzymatic and non-enzymatic reactions. The human body will never
stop to metabolize. This metabolism process will always produce free
radicals, both positive and negative. Metabolic processes such as those that
occur in the respiratory chain, in phagocytosis, in the process of
prostaglandins can produce free radicals14. The above metabolic process will
continue to maintain the homeostasis of the body. Therefore, free radicals will
 12

continue to be formed as waste from processes that support our survival. In

addition, non-enzymatic reactions such as organic compounds that react with
oxygen can also become free radicals when they pass the ionic reactions
stage. Free radicals that accumulate in the body can harm the body. Aging is
indeed normal for everyone. Some internally generated sources of free
radicals are14:
1. Mitochondria
2. Xanthine oxidase
3. Peroxisomes
4. Inflammation
5. Phagocytosis
6. Arachidonate pathways
7. Exercise
8. Ischemia/reperfusion injury
Some externally generated sources of free radicals are14:
1. Cigarette smoke
2. Environmental pollutants
3. Radiation
4. Certain drugs, pesticides
5. Industrial solvents
6. Ozone
Free radicals produced by each of the above processes will have a
different impact on the body that leads to oxidative stress in the event of an
imbalance in the concentration of free radicals produced and lead to aging.

2.3 The Effect of Oxidative Stress on Aging

Oxidative stress is the unbalance of pro-oxidants which likely the free
radicals and antioxidants for neutralizing the free radicals. The unbalance of it
causes by excessive of the free radicals (mainly produced by ETS
mitochondrion) or lack of antioxidants that will caused oxidative damage to
macromolecules (proteins, lipid, carbohydrates, and nucleic acid). Oxidative
stress will caused DNA lesions, such as DNA strand breaks and transverse
 13

mutations, resulting accumulation of irritative effect from free radicals and

failure in tissue homeostasis leading to premature skin aging.15 Oxidative stress
in skin play a major role in the intrinsic aging even more in extrinsic aging,
althought the result in skin are quiet different in dermis and epidermis.16 Skin
aging is characterized with changing of visual appearance (elasticity, texture,
etc conditions like solar radiation and tobacco smoke which induced the free
radicals c). As we know that skin covers all our body, so skin is exposed to
many environmental alled extrinsic aging. Solar radiation (UV- radiation) that
have many waveleght, which is UV-A and UV-B will directly go through our
skin that will produce free reactive radicals, causing oxidative damage in DNA
mitochondrium, DNA nucleus, and disruption of extracelullar matrix (ECM)
resulting in skin aging (usually called as photoaging). This photoaging
accelerates the degradation of ECM which these UV-A and UV-B will produce
reactive oxygen species (ROS) that will leads to the expression of the
transcription factor activator protein 1 (AP-1). This protein will inhibit the
collagen production in the ECM and increase degradation of the ECM, leading
to aging.

Figure 2.2 Sun radiation

Source: ncdc.noaa.gov
Tobacco smoke have tar and gases that really rich in radical oxidants and
the other various compound capable to induces of various ROS like superoxide
anion that cause oxidative stress in cell membrane and leading to apoptosis of
the cell (cell death).17
 14

2.4 The Prevention of Oxidative Stress and Aging

1. Lifestyle
Oxidative stress and aging can be prevented by adopting a healthy
lifestyle, such as not smoking, not drinking alcohol, and regulating body
weight to prevent obesity. Oxidative stress is positively associated with
smoking lifestyle and cotinine (the major metabolite of nicotine) levels.18
Smoking will result in an increase in free oxygen radicals through increased
exposure to cumulative reactive oxygen species (ROS). Increased oxidative
stress due to smoking can occur due to the content of free radicals found in
cigarettes. The tar content in cigarettes contains semiquinone free radicals,
which can reduce oxygen to superoxide that will cause dismutation and
form hydrogen peroxide when dissolved in aqueous solutions such as lung
fluid and blood plasma.19
Previous studies states that alcohol can increase oxidative stress
levels. Consumption of ethanol can increase free radicals in the body due to
ethanol can stimulate cytochrome P450 produce superoxide radicals.
Acetaldehyde produced from oxidation ethanol binds to glutathione
decrease the ability of deep glutathione protect the body from H2O2 so that
it can increase the formation of hydroxyl radicals.20 Previous studies also
show that there is an increase of oxidative stress in obese individuals
compared to normal weight individuals that characterized by increased lipid
peroxide; such as MDA (malondialdehyde) products. Superoxide dismutase
(SOD) is an antioxidant enzyme that acts as the first defense system against
free radical compounds. However, some studies show antioxidant activity
such as SOD in obesity is lower than at normal body weight. Consuming
foods / drinks rich in antioxidants can increase the body's antioxidant
defenses which can further reduce oxidative stress.21
2. Diet
A healthy diet full of anti-aging foods can boost skin quality,
improve immunity, and more. Also, keep the healthy food can reduce
oxidative stress because our body become healthy.
 15

3. Exercise
Lots of things can be induced through exercise. There are lots of
evidence that shows how physical activity and exercise fights back aging.
Physical activity can be defined as bodily movements that are coordinated
by skeletal muscles which will increase energy expenditure over resting
condition. Higher levels of physical activity can result in the reducing of
risks that can cause mortality and increase longevity.
Exercise plays a role in maintaining genomic stability. Exercise can
improve DNA repair mechanism which one of the reason that can affect
aging. Studies said that aerobic exercise induce autophagy which can
prevent the loss of strength and muscle mass through modulation of IGF -
1, protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and
Akt/Forkhead box O3A signaling pathways.
The World Health Organization has identified that physical
inactivity is the fourth leading risk factor of worldwide mortality. Through
this research, it is believed that physical activity and exercise training can
reduce age-associated diseases or even aging itself.
Exercise also mitigates mitochondrial aging and interrupts the vicious
cycle of oxidative damage by stimulating mitochondrial biogenesis and
enhancing mitochondrial oxidative capacity
4. Antioxidants
Ascorbic acid or vitamin C is one of nutrient antioxidants that can
prevent the oxidative stress and aging. Vitamin C is a water-soluble
antioxidant that can be found in raw broccoli, spinach, strawberries,
oranges, tomatoes, etc.5 Vitamin C is a chain breaking antioxidant as a
reducing agent or electron donor. Vitamin C compounds are able to donate
hydrogen atoms to DPPH free radicals to form a stable reduced DPPH
compound (DPPH-H). The higher the vitamin C content, the more DPPH
radicals react so that the concentration decreases. The greater the reduction
in DPPH concentration, the higher its antioxidant activity.6. Vitamin C also
can inhibits lipid peroxidation and promotes the regeneration of α-
tocopherol.
 CHAPTER III
SUMMARY

3.1 Conclusion
Based on our research that have been done, we can conclude several
things. Those are:
1. Oxidative stress is a condition when free radicals and the stabilizing agent’s
antioxidant enzymes in the body are imbalance. The main factor of
oxidative stress are lack of antioxidants or excess free radicals production.
2. Aging is a result from the impact of the accumulation of a wide variety of
cellular and molecular damage. These changes are neither consistent nor
linear and they are only slightly associated with someone’s age in years.
3. Oxidative stress will caused DNA lesions, such as DNA strand breaks and
transverse mutations, resulting accumulation of irritative effect from free
radicals and failure in tissue homeostasis leading to premature skin aging.15
Oxidative stress in skin play a major role in the intrinsic aging even more in
extrinsic aging, althought the result in skin are quiet different in dermis and
epidermis.
4. Oxidative stress and aging could be prevented by healthy lifestyle, diet,
routine exercise, and consume enough antioxidants.

16
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