Glycative Stress Research
Online edition : ISSN 2188-3610
Print edition : ISSN 2188-3602
Received : April 15, 2018
Accepted : May 2, 2018
Published online : June 30, 2018
doi:10.24659/gsr.5.2_86

Review article

Olive oil and skin anti-aging.
Masamitsu Ichihashi 1), Hiroki Yanagi 2), Satoshi Yoshimoto 2), Hideya Ando 2),
Makoto Kunisada 3), Chikako Nishigori 3)
1) Arts Ginza Clinic, Tokyo, Japan
2) Okayama University of Science
3) Postgraduate School of Medicine, Kobe University, Hyogo, Japan

Abstract

This study compiled functional components and effects of olive oil, focusing on the anti-aging effects in the field of
dermatology. Olive oil is a type of vegetable oil that contains many monounsaturated fatty acids (MUFA) such as oleic acid.
Olive extracts provide beneficial anti-oxidative effects, containing phenolic compounds such as tyrosol, hydroxytyrosol,
caffeic acid, and oleuropein. Health promotion effects of olive oil are well-known in the Mediterranean diet, which has gained
worldwide attention for its contribution to longevity. Olive oil reduces the risk of ultraviolet (UV)-induced carcinogenesis,
affecting DNA damage with the formation of 8-OHdG due to UV exposure. Furthermore, olive oil can induce beneficial
epigenetic modifications with effects of MUFA on DNA methylation and oleuropein on histone acetylation. It has been also
reported that olive oil is effective for diabetic patients, characterized by severe glycative stress, to maintain the function of
pancreatic β-cells, to lower blood glucose level, and to inhibit the formation and to promote the degradation of advanced
glycation end products (AGEs). Therefore, olive oil plays a significant part in this rapidly aging society worldwide to help
people retain and restore youth. Looking young could be inspiring and encouraging to live a positive life.

KEY WORDS: Olive (Olea europaea), oleuropein, skin, ultraviolet exposure, photoaging

1. Introduction
Risk factors to accelerate aging are diversified. Current
theories have demonstrated genomic instability, telomere
attrition, epigenetic alterations, damage of nucleic acid byreactive oxygen species (ROS), accumulation of abnormal
protein, mitochondrial dysfunction, stem cell exhaustion andaltered intercellular signal pathways. A theory was presented
in 2012 which stated that mitochondria, p53, and ROS are
mutually related to inducing aging 1).
Basic and clinical research has been continued over a long
period with a great interest in photoaging, which is referred
to as the acceleration of skin aging due to solar ultraviolet
radiation. The risks of genetic injuries of skin cell nucleus
due to ultraviolet radiation are unavoidable as long as humans
live a life under the sun light. The theory has been acceptedthat DNA damage to skin tissues induces inflammation, which
damages cells and tissues. The repetition of DNA damage
induces gene mutations, and the repetition of inflammation
Contact Address: Masamitsu Ichihashi MD, PhD
Arts Ginza Clinic
2 -20 -15 Shinbashi, Minatoku, Tokyo 105 - 0004 Japan
TEL: +81-3- 6228-5025 eMail: mm_ichihashi@hotmail.com
Phone/Fax: + 81-774 - 65 - 6394 E-mail: myagi@mail.doshisha.ac.jp
Co-authors: Yanagi H, t17am03yh@ous.jp; Yosimoto S, t17sd03ys@ous.jp;
Ando H, ando@dac.ous.ac.jp; Kunisada M, kunisada@med.kobe-u.ac.jp;
Nishigori C, chikako@med.kobe-u.ac.jp

leads to cellular senescence in skin 2, 3). Further, ROS are
inevitably produced as a byproduct in minute cytoplasmic
organs, mitochondria, which generate the energy necessary
for cells to live. Therefore, excessive production of ROS,
exceeding the anti-oxidant capacity of a cell, induces
irreversible damage to cells and nearby tissues. Consequently,
it is indicated that ROS are one of the major causes forskin aging 4-6). Recent studies have revealed that chemokine(C-X-C motif) ligand 1 (CXCL1) plays an important part in
the process of inflammatory responses or carcinogenesis,
which is caused by ultraviolet (UV)-induced DNA damage.
Possibilities are suggested for the regulation of inflammation
through the involvement of chemokine for the purpose ofdelaying aging 7).
More than twenty years have passed since the remarkableeffectiveness of olive, Olea europaea, have been realized. It
was known that olive oil has a strong anti-oxidative effect.
Focusing on 8-hydroxy-2’-deoxyguanosine (8-OHdG), which
was formed due to the oxidation of a base, a gene component,_ 86 _

Glycative Stress Research 2018; 5 (2): 086- 0 94(c) Society for Glycative Stress ResearchGlycative Stress Researchhydroxytyrosol (HT,) caffeic acid, and oleuropein, which
are characterized by their anti-oxidative effects and otherbiological activities for good health. In particular, EVOO
consumption for several months increases the expressionof macrophages and promotes the decrease of cholesterol
mediated by high-density lipoprotein (HDL) 11). Furthermore,
there is a possibility that olive oil can contribute to thealleviation of problems related to cognitive impairment or
muscle weakness in the aging society, as results of animal
experiments have suggested 12, 13). Moreover, in vitro studies
have indicated that olive oil phenols have beneficial effects
to control the signal transmission related to inflammatory
response, prevent apoptosis and regulate the energy metabolic
pathway of the aging process 14, 15).

examinations were conducted to discover whether 8-OHdG
would be produced in skin cells under UV irradiation. It wasclarified that 8-OHdG appeared in the human epidermis
after UVB radiation at the degree of obtaining a suntan,
using anti-8-OHdG antibody 8).
Experiments were performed with mice to clarify
whether UV photocarcinogenesis was affected by oxidized
bases in DNA, other than cyclobutane pyrimidine dimers(CPD) and 6 - 4PP, which have been regarded as themain causes of UV-induced skin cancer. To confirm theinvolvement of UV- induced 8-OHdG in UV- induced
skin carcinogenesis, applying olive oil to the skin was
assumed to reduce the formation of 8-OHdG and suppress
carcinogenesis due to the strong anti-oxidative effect 9). An
increasing number of research laboratories have reported
the effectiveness of the health promotion of olive oil sincethat time. Consequently, theories have been established toprove that olive oil is effective and has dietary benefits which
contribute to good health in everyday life. This research
reported the results of the experiments, which we conducted,
with some recent literature reviews on the health effectsof olive oil relating to lifestyle-related diseases such as
cardiovascular diseases and diabetes.

3. Anti-aging effects of olive oil
It is expected that DNA damage would be a major factor
of inducing senescent cells and identifying the mechanismof DNA stabilization of olive oil would bring meaningfulunderstanding of its anti-aging effects. In particular,
mitochondrial DNA is more susceptible to oxidative attack
than nuclear DNA, as is widely known. It has already beenreported that the administration of olive oil lowered theprobability of DNA damage in peripheral blood cells 16). It isconsidered that H 2 O 2 produced in cells by UVA is a cause ofcellular senescence 17, 18). It has been proven that oleuropein
and other compounds contained in olive oil reduce DNA
damage 19) and scavenge ROS ( Fig. 1 ). However, it is assumed
that a dose of olive oil that we ingest on a daily basis, whichcontains low density phenol compounds, can inhibit the cell
damage induced by H 2 O 2 20). Accordingly, oral administrationof olive oil can be said to have similar effects of applying
a sunscreen agent to prevent sunburn, although SPF (sunprotection factor) is low as 1. 5 to 2, as shown in otherantioxidant materials orally administered.

2. Constituents and health effects of olive oil
The health effects of olive oil are well-known worldwide
with a great deal of attention on the Mediterranean dietcontributing to longevity. Olive oil is a type of vegetable oilthat contains many monounsaturated fatty acids (MUFA),
mainly oleic acid 10). Olive oil is understood to reduce theincidence rate of cardiovascular diseases and cancers,which are the leading causes of death at present. Further,immunological surveillance involving human subjects showedthat virgin olive oil (VOO) and extra virgin olive oil (EVOO)
contain abundant phenolic compounds such as tyrosol,

N= 3＊＊ p < 0.01(vs.Oleuropein)

Anti-oxidant activity (μmol TE/g)

50,000＊＊40,000＊＊30,00020,000＊＊10,0000
Oleuropein

Vitamin C

Fig. 1. Anti-oxidant activities determined by ORAC assay

NAC

Resveratrol

Oleuropein showed a stronger radical scavenging activity compared with vitamin C, and NAC and resveratrol
had the strongest ORAC among our studies. The values were expressed as μmol Trolox equivalents (TE) per
gram of each anti-oxidant. The bars indicate mean values of triplicate determinations ± SD. ORAC, oxygen
radical absorbance capacity; NAC, N-acetyl cysteine; SD, standard deviation.

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Olive Oil and Skin Anti - Aging.

While mitochondria produce ATP, ROS are inevitably
produced as a byproduct. MUFA is less likely to be oxidized
than polyunsaturated fatty acid, which is susceptible to ROSinduced damage of fatty acid in cell membranes. Therefore,
olive oil is favorable to mitochondria.
Telomere attrition is one of the hallmarks of aging.
Telomeres are shortened with aging and are deeply related
to life-span, which is widely understood due to the findingsthat replicative DNA polymerases lack the ability to replicatecompletely the terminal ends of linear DNA molecules 21, 22).
Drinking alcohol and smoking accelerate telomere attrition,
as was previously reported 23). It has also been reported that
Greek people, who consume a Mediterranean diet with
abundant MUFA as a daily food, have longer telomeres inperipheral leucocyte than Dutch people, who have a different
daily diet. Further research is awaited to examine theassociations of telomere shortening with production of ROS
or apoptosis 24, 25).
Recent investigations showed that telomeres weredamaged and bases with a short GGATTG array appeared incells exposed to ultraviolet radiation. Repair of DNA damage
was induced via SOS response 26, 27). It is considered that
telomeres are always engaged in information transmission
and contribute to the maintenance of life in cells 28).
Epigenetics has a great number of factors to influencecell functions. Among these factors, diet is regarded as animportant factor 29). It has been reported that MUFA affects
the methylation of DNA and oleuropein affects histone
acetylation, especially hyperacetylation of H3 histone in
the Mediterranean diet 30). In addition, lipid metabolism isimportant from the viewpoint of aging. It is said that withthe total amount of Mediterranean food for one year, themethylation of SCD-1 (stearoyl CoA desaturase-1) genepromoter was accelerated 31). This phenomenon means thatthe mechanism of the obesity inhibitor of the Mediterranean
diet can be partly explained by epigenetic functions. Recent
studies on the association between miRNA and cerebral
apoplexy reported that ingestion of the Mediterranean diet
reduced the degree of risks of people who had rs13702
Callele carriers of a high-risk factor of cerebral apoplexy 32).
It is also accepted that the Mediterranean diet and olive oil
are involved in the prevention of coronary heart diseases,
altering the expression of genes related to arteriosclerosis 33).
The accumulation of abnormal protein is regarded as a
critical cause of Parkinson’s disease and Alzheimer’s disease(AD). Some in vitro studies of the influences on cells byphenolic materials reported that hydroxytyrosol, oleuropein
and oleuropein aglycone, which are contained in olive
oil, inhibited the fibril change of Tau protein 34). Further,
it is known that olive oil activates SIRT1 and exerts antiaging effects 35, 36). There was an encouraging report of anin vitro experiment where the administration of oleuropein
enabled the subject to maintain proteasome functions for along period, prolonging the life-span of cells and extending
the period to reach senescence by approximately 15% 37).
Removal of abnormal protein is crucial to maintain the
homeostasis of an organism. Olive oil is less susceptible
to endoplasmic reticulum (ER) stress, which is induced bysaturated fatty acid, as olive oil contains a large amount ofshort-chain unsaturated fatty acid. As a result, abnormality is
unlikely to appear in protein folding 38). Advanced glycation
end products (AGEs) are a type of abnormal protein andare formed due to glycative stress. It has been reported
recently that luteolin, which is an extract of olive oil,inhibits the formation of AGEs 39), and oleuropein, which ismain compound of olive oil, promotes the degradation of
α-diketone structure of AGEs and accelerates the metabolism
of AGEs 40).
Developed and developing nations, including Japan,
have health problems not only at present but also in the
future, among which countermeasures against diabetes
would be the greatest concern to focus on. Insulin resistance,
which is strongly associated with aging, is both a reason
for and a result of obesity. Countermeasures must be taken
immediately. We are deeply and seriously concerned about
the present medical environment for diabetes in Japan.
Generally, it is not until people are diagnosed as diabetic that
medical treatments start, such as pharmacotherapy. People
with pre and preliminary diabetes must be encouraged totake preventive measures, eating a healthy diet and becoming
physically active to control the progression of the disease.
It is necessary to help people have a better understanding
for the importance of prevention and treatment other than
medications. Moreover, it is important to educate young
children to realize that appropriate diet, and excise on a daily
basis enables the prevention and the onset of lifestyle-relateddiseases such as diabetes. The decline of somatotropic
hormone and insulin-like growth factor-I (IGF-I) withaging suggested that nutrition uptake similar to young
generations has an abnormal metabolisms due to aging.
Since approximately 1992, there have been reports thatexperiments with diabetic rabbits exhibited the anti-diabetes
effects of olive oil. The point is that the administration ofolive oil can lower blood glucose level and reduce oxidative
stress 41,42). Further, a randomized, double-blind, placebocontrolled trial was conducted in 2013 with patients withobesity among research participants. This trial recognizedthat the administration of olive leaf extracts for 12 weeks
improved insulin sensitivity and accelerated the functionsof pancreatic β-cells 43). In addition, oleuropein reduced theoxidative stress related to diabetes 44). Observing the relation
between longevity and olive oil, some studies showed that
EVOO regulated mTOR pathways and reduced cancer cell
multiplication in cultured cells 45, 46). It is considered that olive
oil, which contains a large amount of short-chain unsaturated
fatty acid, is favorable for the retention of mitochondria
activity, and is expected to play a role as one of the foods foranti-aging.
Regarding cognitive impairment, olive oil is reported
to reduce the deposition and increase the clearance ofamyloid-β, which is regarded as a cause of Alzheimer'sbasket cells (AD) and a critical cause of the onset of AD 47).
There is a great deal of in vitro research regarding humanskin, suggesting that polyphenol contained in olive oil iseffective in the prevention and treatment of AD.

4. Preventive effects of olive oil on
ultraviolet radiation carcinogenesis
UV radiation of sunlight is a major cause of skin cancer
and photo-aging. The energy of UVB (wavelength, 290-320nm) is directly absorbed by bases, which form genes, andinduces cyclobutane pyrimidine dimer (CPD), a typical typeof UV-induced DNA damage. The CPD formation by UVA(wavelength, 320- 400 nm) is remarkably low in comparison
with UVB, yet induces mutations, which is particular in
UVA 48, 49). However, the ultraviolet rays, which reach thesurface of the earth, deliver its energy to energy-absorbing_ 88 _Glycative Stress Researchmaterials, which exist in skin cells and tissues. The energy istransferred, via transfer of electron or activation of oxygen,to nucleic acid, protein, lipid, and carbohydrate and induces
damage in these components of skin. As a result, skin cells
have diverse reactions, such as inflammatory responses via
signal transduction, leading to immunological abnormalities
and destruction of dermal components which initiate photoaging of the skin 50, 51).
We had an interest in reports that ROS were involved in
UV-induced carcinogenesis. We studied the effect of UV on
8-OHdG, an oxidized guanine product, induced via electrontransfer and ROS. Another inspiring piece of researchsuggested that oral administration of green tea with highanti-oxidant capacity or Vitamin E lowered the incidenceof UV-induced skin cancer in experiments with mice 52, 53).
Mutations of p53 and ras in UV-induced cancer tissuesof humans and mice were G : C → T : A transversion, andthere was a possibility of 8-OHdG involvement. When we
began investigating olive oil, some studies in epidemiology
with human subjects had already reported that research
participants who ingested ample vegetables with high antioxidative activity had low incidence of skin cancer 54).
However, as far as is known, there were no research data atthat time which clearly showed that 8-OHdG ( Fig. 2 ) was
involved in ultraviolet radiation carcinogenesis. Firstly, we
conducted an experiment with human and mouse skin, using
artificial UVB radiation to clarify whether 8-OHdG would
appear in the nucleus of skin, by immunohistochemical
staining method with anti- 8- OHdG antibody ( Fig. 3 ) 8).

8-OHdG chemical structure

O
HO
HOCH 2
O

N
N

N
N

NH 2

HO
8-Hydroxy-2 -deoxyguanosine (8-OHdG)
Fig. 2. Oxidation of base Guanine (G)Base guanine exists as a gene component or gene pool in cell
nucleus. Guanine is oxidized via electron transfer or oxygen
molecule due to ultraviolet (UV) radiation, and 8-hydroxy-2’deoxyguanosine (8-OHdG) is produced. Oxidative DNA damageis repaired by an enzyme, OGG1 (coding 8-oxoguanine-DNA
glycosylase).

It was proven that three hours after UVB irradiation, agreat number of 8-OHdG positive cells were observed in
the UVB irradiated epidermis. Antibody positive cells,
however, were not observed at 72 and 96 hours after
UV irradiation, which indicated that 8-OHdG had been
repaired. Next, to study the possible inhibitory effects ofolive oil on UVB-induced 8-OHdG, olive oil was applied
to mice skin before and after UV irradiation. To confirm
its effects on DNA damage induced by UV light, CPD and
8-OHdG formed in epidermal cell nucleus were analyzed
immunohistochemically, using antibodies against CPD and
8-OHdG. Furthermore, either before or after UV radiation,
150 μl of oleuropein ( Fig. 4 ), hydroxytyrosol, or squalene,
which were known as components of olive oil, were applied
to mouse skin. Following this, the amount of CPD and
8-OHdG formation was compared among the groups. The
inhibitory effects of olive oil application on the formation of
CPD were not observed either before or after UV irradiation.
However, in the formation of 8-OHdG, the group with olive
oil applied immediately following UV irradiation revealed
that the number of 8-OHdG positive cells had been distinctly
reduced. Contrarily, as for the group with the olive oilapplication prior to UV irradiation, no effects were shownto decrease the number of 8-OHdG positive cells ( Fig. 5 ).
As for the examinations of olive oil component, only theoleuropein showed a reduction of 8-OHdG positive cells
applied only after UV irradiation ( Fig. 6, unpublished data).
Afterward, a comparative experiment was conducted on
the number of days until the onset of skin cancer among threegroups. Group Ⅰ: UV irradiation, Group Ⅱ: application of olive
oil before UV irradiation, and Group Ⅲ: application of olive
oil after UV irradiation. Mice underwent UVB irradiation of
343.0 mJ/cm 2 on the skin three times a week for 32 consecutive
weeks. Thirty-two weeks after the start of UV irradiation,
the number of neoplastic cells per mouse was 8.53 in Group Ⅰ
of UV irradiation without olive oil application, 9.53 in GroupⅡ of application before UV irradiation, and 3.36 in GroupⅢ of application after UV irradiation. These data confirmedthat the application of olive oil after UV irradiation
significantly reduced the number of tumors ( Fig. 7 ) 9).
From these data, we believed that oleuropein, whichis contained in olive oil with strong anti-oxidant effects,
inhibited the formation of UV-induced 8-OHdG. The effectsof oleuropein application led to the reduction of skin tumor
formation in mice. In addition, it was recognized that olive
oil, which had been irradiated with UVB 343.0 mJ/cm2
once, had lower anti-oxidant effects, because unlike fresh
olive oil, the formation of 8-OHdG was not reduced by
the application of UV-treated olive oil to the skin of UVirradiated mice. However, in these experiments with mice,detailed examinations on different doses of UV or different
periods between UV irradiation and application of olive oil
were not performed.
These investigations are believed to have revealed
that DNA oxidative damage by 8-OHdG was significantly
involved in UV-induced carcinogenesis, in addition to
CPD being regarded as the main cause of UV-induced
carcinogenesis, which formed instantaneously with UVradiation. Subsequently Kunisada et al. conducted research
on UV-induced skin cancer formation using OGG1 geneknockout mice, which were deficient in the repair ofoxidative base damage, to show that 8- OHdG, oxidative
DNA damage was deeply correlated with UV-induced
carcinogenesis ( Fig. 8 ) 55, 56).

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Olive Oil and Skin Anti - Aging.

Fig. 3. 8-OHdG is formed in skin keratinocyte due to UV radiation)

a: target skin without UV irradiation. b: skin at 30 minutes after UV irradiation. c: skin at 24 hours after UV irradiation;
many positive cells remain. d: skin at 72 hours after UV irradiation; almost all 8-OHdG positive cells were not observed,
which revealed that damage had been repaired. Findings of skin samples were collected by punch biopsy 30 minutes after
UV radiation of a double dose of minimal erythema dose (MED) to the inside section of the upper arm of a human. Samples
were processed with paraffin after formalin- fixation and was followed by being dyed with 8-OHdG antibody. Agreat
number of 8-OHdG were formed in the nucleus dyed blown. Photos are quoted from Reference 8). 8-OHdG, 8-hydroxy-2’deoxyguanosine; UV, ultraviolet.

Dihydroxy
phenol moiety

HO

Oleuropein
Secoiridoid
glycoside moiety

O

C
COCMe

HO
O

Fig. 4. Chemical constitution formula of oleuropein

OGic

Oleuropein is a smallmolecule contained in olive oil and has anti-oxidative activity. Gic, glucose.

_ 90 _Glycative Stress Research

Fig. 5. Effects of olive oil application on DNA damage formation (CPD: A-C and 8-OHdG: D-F) whichappeared in the epidermal cell nucleus of mice back after UVB irradiation of 3.43 kJ/m2

Two sets of mouse skin samples were collected 30 minutes after irradiation. Samples were taken from mice skin where
olive oil had been applied immediately before irradiation (B, E) and also from mice skin where olive oil had been applied
immediately after irradiation (C, F). Skin samples treated with the olive oil immediately after UVB irradiation showed asignificantly lower number of 8-OHdG positive cells, but no change in the number of CPD positive cells. Photos are quoted
from Reference 9). CPD, cyclobutane pyrimidine dimers; 8-OHdG, 8-hydroxy-2’-deoxyguanosine; UV, ultraviolet.

Fig. 6. Inhibitory effects of oleuropein on the formation of 8-OHdG

Oleuropein, in the amount of 0.1 mg (0.1 mL), was applied to the mice skin immediately after UVB irradiation of 3.4 kJ/m 2.
The number of positive 8-OHdG cells and 8-OHdG antibody 30 minutes after UVB irradiation was distinctly smaller than
the target skin without olive oil application. 8-OHdG, 8-hydroxy-2’- deoxyguanosine; UV, ultraviolet.

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Olive Oil and Skin Anti - Aging.

Fig. 7. Influences of olive oil application on the UV-induced carcinogenesis in skinMice were classified into four groups: 1) group with UVB irradiation of 3.43 kJ/m 2, 2) group with application with 150 μL
of olive oil immediately prior to UV irradiation, 3) group with application of olive oil immediately following UV irradiation,and 4) group with application of UVB-treated olive oil (3.43 kJ/m 2) immediately following UV irradiation. All groups had
15 mice, compared in the shortest period of days by the formation of tumor, the number of tumor-bearing mice and thenumber of tumors per mouse 32 weeks after the irradiation. Groups with olive oil application before and after irradiation
showed inhibitory effects of carcinogenesis, especially the group with application immediately after irradiation showedstrong inhibitory effects. UV, ultraviolet.

Fig. 8. Influences on UV-induced skin carcinogenesis by repair enzyme on oxidative base damages

Comparison experiments in carcinogenesis were performed between OGG1 knockout (KO) mice and normal mice,
irradiated with UVB (2.5 kJ/m 2) three times a week for 40 weeks and observing the carcinogenesis process for 45 weeks
after the start of irradiation. Tumors clearly appeared sooner in KO mice (30 weeks). As for normal mice, tumor-bearing
mice appeared at 36 weeks. Comparing the time for each group when 60% of specimens exhibited tumors, the KO micegroup was 35 weeks and normal mice group was 41 weeks. Forty-five weeks after irradiation, both groups had 100 % tumor
occurrence. Moreover, the mean of the number of tumors per mouse was 3.7 in the KO mice group and 1.71 in the normal
mice group. The KO mice group had approximately twice as many tumor-bearing mice as the normal mice group. Photos
are modified from References 5 and 6). UV, ultraviolet.

_ 92 _Glycative Stress Research

5. Future perspective:
applying olive oil effects to thephoto-aging inhibition in skin
It is believed that further studies are neccessary to
examine influences to skin tissues by oleuropein and othersmall-sized materials contained in olive oil, focusing on
the anti-oxidative and anti-glycative effects. Considering
the rapidly aging society, the role of olive oil is significant,especially to help individuals retain and restore youth.
Looking young may be inspiring and encouraging to live
a positive life. We hope to fully understand the influencesof UVA and UVB radiation on ROS formation in cells,
mitochondria activities and apoptosis. How longevity ofskin stem cells is affected by olive oil must be clarified.

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The researches that we have conducted strongly suggest
the importance of ideal conditions to apply olive oil toskin against environmental stresses. A great number of
researchers in the world also have found preventive effects
for lifestyle-related diseases using oral administration ofolive oil. By carefully observing and analyzing these researchdata, we would like to examine the optimum condition ofolive oil for skin health both in oral administration andtopical application to the skin.

Conflict of Interest Statement

We state that the performance of this study entailed noissues representing a conflict of interest.

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