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ANTI-AGEING NATURAL HERBS: A SYSTEMIC REVIEW

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Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
et.al
Sept’18
Ind Res J Pharm & Sci|2018: Sept.: 5 (3)
1589
ANTI-AGEING NATURAL HERBS: A SYSTEMIC REVIEW
Atyurmila Chakraborty*, Mitali Sahoo, Saumendu Deb Roy, Ramesh Kumari Dasgupta
Dept. of Pharmacognosy, Bharat Technology, Uluberia, Howrah
ABSTRACT: Skin is the largest organ of the integumentary system. The overall well-being& perception of health
in humans, very much depends on skin health & beauty. Skin plays a vital role in immunity& protects the body
against pathogens, maintains water and electrolyte balance & also regulates body temperature. Epidermis is the
protective covering over the body surface which serves as a barrier to infection. Thinning of this epidermal layer,
loosening of collagen & elastic fiber, leads to the wrinkle formation and causes ageing. Ageing occurs due to the
intrinsic factors like genetics, cellular metabolism, hormone & metabolic process or extrinsic factors like sun
exposure, smoking, diet and pollution. In this era of modern science, people choose natural herbs rather than plastic
surgery or laser therapy for not only looking younger but also to reduce complications. Herbs help in biological
functioning of the skin & supplies nutrients required for healthy skin. Herbs contain several phytochemicals like
carotenoids, terpenoids, polyphenols which possesses anti-aging activity. A few herb which shows anti-aging
activity includes, Aloe, Cucumber, Ginseng, Honey, Wheat, Liquorice, Arjuna, Jatamansi etc.
KEYWORDS: Herbs, Anti-aging, Skin, Phytochemicals
Corresponding Author: Atyurmila Chakraborty
E-Mail: milachakraborty1996@gmail.com
Phone: +91-8617390669
REVIEW
Submitted on: 12.08.18; Revised on: 19.08.18; Accepted on: 28.08.18
Indian Research Journal of Pharmacy and Science; 17(2018)1589-1598
;
Journal Home Page: https://www.irjps.in
DOI: 10.21276/irjps.2018.5.3.4
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Ind Res J Pharm & Sci|2018: Sept.: 5 (3)
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INTRODUCTION:
Ageing is an unavoidable process for all living
organisms. Ageing phenomena starts from the
moment of our birth and is markedly visible on the
skin in progressive years. Based on increased life
expectancy, it is estimated that there will be over 1.2
billion older adults (over 60 years old) worldwide in
2025.
1
Ageing is at least partially attributed to an age
related increase in weakness and immunosenscence
and perhaps mitochondrial dysfunction.
2
Maintenance of the physical function in older adults
is therefore a major public and clinical priority. In
humans the skin is the tissue most markedly affected.
Skin is a protective barrier against the external
environment. Its function is to regulate temperature,
fluid balance & to protect from harmful microbes and
UV radiation in sunlight. Two types of skin ageing
exist: age-dependent/chronological ageing and
premature ageing/photoageing. Photoageing is caused
by extrinsic factors and includes signs such as a
leathery appearance, dark/light pigmentation and
deep furrows.
Natural ageing is visible as wrinkling
of the skin. The skin is divided into three layers; the
epidermis, dermis and subcutaneous tissue.
3
The extracellular matrix (ECM) is the outermost part
of the skin and is composed of fibroblasts and
proteins including collagen and elastin. After the age
of 20, its symptoms appears as the collagen content
per unit area starts decreasing, there is 1% decrease
in collagen content per unit area of the skin every
year. The ECM provides a structural supporting
structure which is essential for growth and elasticity
of the skin and plays an important role in the
maintenance of physiological functions of the body.
Degenaration of the ECM has directly been linked to
skin ageing and is correlated with an increase in
activity of certain enzymes involved in skin ageing,
which includes hyaluronidase, elastase and
collagenase. Collagen is one of the major building
blocks of the skin, which is responsible for the
elasticity and strength of the skin and maintains its
flexibility. Hyaluronic acid performs a role in
retaining the moisture of the skin, as well as its
structure and elasticity. It also facilitates the
exchange of nutrients and waste products and is
participating in rapid tissue proliferation,
regeneration and repair. With ageing, collagen,
elastin and hyaluronic acid levels declines, leading to
a loss of strength and flexibility in the skin which
results in visible wrinkles associated with the
thickened epidermis, mottled discoloration, laxity,
dullness and roughness of the skin.
4
Reactive oxygen species (ROS) play an important
role in many cellular mechanism . When UV
radiation is absorbed by the skin, it leads to enhanced
ROS generation and induction of oxidative stress.
Oxidative damage may lead to lipid peroxide
formation, mitochondrial and DNA damage, and
protein and gene modification which change protein
structure and function. High levels of ROS lead to the
activation of hyaluronidase, collagenase and elastase,
which can further contribute to skin ageing.
5
The enzyme angiotensin 2 also plays a vital role in
photoaging of skin as it involved in healing wounds
and scar formation, appearance of scars leads to
wrinkles. So by using angiotensin converting enzyme
(ACE) inhibitors which prevent the conversion of
angiotensinogen (inactive) to angiotensin (active) we
can decrease the effect of angiotensin 2 induced skin
ageing and wrinkles.
The modern science and technology provides plastic
surgery, laser rejuvenation, and many more invasive
techniques. Noninvasive techniques do not involve
any risks or complications and mostly free of side
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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Sept’18
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effects as compared to the invasive techniques which
are more painful and laborious. Over the last decade,
there has been an increase in the use of herbal
extracts in cosmetics to reduce the ageing process.
The extracts of Aloe Vera, Amla, Turmeric,
Cucumber, Ginseng, Honey, Wheat, Liquorice,
Arjuna, Jatamansi are extensively used in herbal
cosmetic industries due to their skin beneficial
properties.
6
MECHANISM OF SKIN AGING
Extrinsic skin ageing:-
This is caused by environmental factors, such as
exposure to the sun rays, repetitive facial expressions,
gravity, sleeping positions and smoking.
7
Extrinsic
ageing is caused by chronic exposure to UV light, so
it is also known as photoageing.
8
Extrinsic skin
ageing is a collective process and depends mostly on
the degree of sun exposure and skin pigment. With
chronic skin exposure to UV rays, the stratum
corneum layer of skin thickens, the epidermis is
damaged and there is progressive dysplasia with
cellular atypia and anaplasia, reduction in collagen
and degradation of elastic fibres.
9
a. Membrane/ nuclear signaling:-
UV irradiation provokes reactive
oxygen species (ROS) which repress the
activity of enzyme protein tyrosine
phosphatase κ. This enzyme maintains
cell surface receptors of skin, including
receptors for epidermal growth
factor(EGF), interleukin (IL)-1,
keratinocyte growth factor and tumour
necrosis factor (TNF)-α in an inactive
(hypophosphorylated) state.
10
Activated
receptors impel to intracellular
signaling through stimulation of the
stress-associated mitrogen activated
protein (MAP) kinases p38 and c-Jun
amino terminal kinase (JNK). Kinase
activation induces the transcription of
MMPs (matrix metalloproteinase) and
decreases expression of the procollagen
I and III and TGF-β receptors, with
afinal outcome of reduced dermal
matrix formation and hence, it reduces
the synthesis of collagen.
11
Fig.1: Nuclear Signaling
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b. Mitochondrial damage :-
Mitochondria are cellular organelles
that generate energy (ATP) by
compelling oxygen. UV effect on the
mitochondria electron transport chain
produces abundant ROS that can
damage mitochondrial DNA
(mtDNA).The mitochondrial genome
encodes 13 components of the electron
transport chain and oxidative damage
may be foremost to deletions or
rearrangements of the DNA, most likely
due to double-strand breaks which may
affect mitochondrial ability to generate
energy for the cell. It is inferred that the
consequent decrease in mitochondrial
function photodamaged skin leads to
additional accumulation of ROS and
further compromises the cell’s ability to
initiate energy.
12
Fig. 2: Mitochondrial damage.
c. Protein oxidation :-
Oxidative damage can also affect
proteins and photodamaged skin.
Oxidative protein impair may result in
loss or gain of activity (i.e. enzymes),
loss of structural protein function and
increased/decreased susceptibility to
degradation.
13
d. Telomere :-
Telomeres are tandem repeats of a short
sequence TTAGGG. It exists in a loop
configuration. Telomeres become
critically short when these loop is
disrupted by cell division or UV
irradiation. During cell division
telomeres cap (the terminal portion of
chromosomes, preventing the fusion of
telomeres with each other) cannot be
replicated, so the bases of the telomeres
caps are lost with each cell division and
finally enters a state of senescence or
apoptosis. When telomeres are damaged
by UV irradiation the loops
configuration becomes disclosed and
through interaction with the protein
activates the tumour suppressor protein
p53 and other proteins which
responsible for DNA damage and also
induces senescence or apoptosis.
14
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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Fig.3: Telomerase induced skin aging
Intrinsic skin ageing: -
Intrinsic skin ageing, also known as natural ageing
mostly found in sun protected area. It is due to the
passage of time or by the inherited gene, therefore
also termed as chronological ageing. Basically the
molecular machanisms of both the type of skin
ageing (extrinsic and intrinsic) are similar, for
example shortening of telomeres, mutations of
mitochondrial DNA, oxidative stress, genetic
mutations and decrease of many hormone levels.
According to the free radical theory of ageing, ROS,
chiefly commencing from oxidative cell metabolism,
play a notable role in both chronological ageing and
photoageing. ROS influence the transcription factor
c-Jun via MAPK (mitrogen activated protein
kinase).Intrinsic skin ageing as same like extrinsic
ageing and collagen is degraded present in
intrinsically aged skin similar to photoaged skin.
12
Hormonal changes can also alter intrinsic skin
ageing. The exhibition of sex hormones in the
gonads, the pituitary and adrenal glands already
gradually decline in the mid-twenties. The hormone
oestrogen and progesterone start decreasing during
menopause. In particular, the imperfection in
oestrogens and androgens cause dryness, wrinkling,
epidermal atrophy, collagen breakdown and loss of
elasticity.
15
NATURAL HERBS USED FOR ANTI-
AGEING:-
Herbal cosmetics play a leading role in impeding and
reversing ageing of skin. Ingredients present in herbal
cosmetics impact biological functions of skin and it
also provide required nutrition for healthy skin. It
has been estimated that more than 50% of all the
drugs in the world are natural products and their
derivatives, and plant-based health remedies are
promising. The application of herbal anti ageing
products has been proliferated to many folds in
personal care practices. The recent trends in anti-
ageing skin care products is focussed on developing
new plant extracts and botanical ingredients based on
their traditional medicinal uses which leads to the
emergence of several cosmoceuticals that prevent
wrinkles and protect the skin from any kind of
unwanted symptoms.
17
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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NA TURAL ANTI_AGING HERBS
14 , 15 , 16
AL OE V ERA
Biological Source: Aloes are the dried juice of
leaves of Aloe barbadensis, belonging to the family
Liliaceae.
Phyto-constituents: All the varieties of aloe are the
major sources of anthraquinone glycosides. The
principal active constituent of aloe is aloin, which is a
mixture of glycosides, among which barbaloin is the
chief constituent. Along with barbaloin, the drug also
contains isobarbaloin, β- barbaloin, aloe-emodin and
resins.
Ro le i n Anti-ageing:
The leaves of aloes are commonly used in anti-aging
and anti-wrinkle creams and moisturizers. In the
treatment of aging and wrinkles the constituents of
aloe Vera such as aloin A and B have shown the
property to inhibit the activity of collagenase, the
enzyme which causes degradation of collagen fibres.
Fig.5: Aloe Fig.6: Amla
Fig. 4: Mechanism of action of Herbs in Anti-a
geing
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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AMLA
Biological Source: This consists of dried as well as
fresh fruits of the plant Emblica officinalis belonging
to the family Euphorbiaceae.
Phyto-constituents: Amla fruit is a natural source of
vitamin C (Ascorbic acid) and also contains fat,
phyllembelin and tannins. Amla fruit is also rich in
mineral matters like phosphorus, iron and calcium.
Role in anti-ageing:
Amla, being a rich source of vitamin C, is considered
important to slow ageing process. It improves skin
health. Ageing is a cumulative result of damage to
various cells and tissues, mainly by oxygen free
radicals. Vitamin C is a scavenger of free radicals
which breaks them down.
TURMERIC
Biological Source: Turmeric consists of dried as well
as, fresh rhizomes of the plant Curcuma longa
belonging to the family Zingiberaceae.
Phyto-constituents: Turmeric contains a yellow
coloured substance known as curcuminoids. The
chief component of curcuminoids is known as
curcumin (50-60%). It also contains volatile oil,
resin, camphor, camphene etc.
Role in anti-ageing:
The chief constituent of Turmeric is curcumin which
acts as a superoxide scavenger & as a singlet oxygen
quencher. Therefore, the anti-ageing property of
Turmeric is mainly due to the curcumin.
Fig.7: Turmeric Fig.8: Honey
HONEY
Biological Source: Honey is a sugar secretion
deposited in honey comb by the bees, Apis mellifera
and other species of Apis, belonging to the family
Apidae.
.Phyto-constituents: Honey is an aqueous solution
of glucose (35%), fructose (45%) and sucrose (2%).It
also contains maltose, gum, polyphenols, flavonoids,
vitamins, proteins etc.
Role in anti-ageing:
The antioxidant property of Honey is due to the
phenolic compounds (benzoic acid and cinnamic
acid) and flavonoids present in it, which helps to
prevent wrinkles in our skin.
GINSENG
Biological Source: Ginseng is the dried root of
various species of Panax, like P. ginseng (Korean
ginseng), P. japonica (Japanese ginseng), P.
notoginseng (Chinese ginseng), belonging to the
family Araliaceae.
Phyto-constituents: Ginseng contains a mixture of
several saponin glycosides, belonging to triterpinoid
group. These are Ginsenosides, Panaxosides and
Chikusetsusaponin which are responsible for various
activity of ginseng.
Role in anti-ageing:
The chief constituent of Ginseng is Ginsenoside
which is responsible for the anti ageing activity of the
ginseng. It improves the blood circulation and skin
tone and also moisturizes the skin.
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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Fig.9: Ginseng Fig.10: Liquorice
LIQUORICE
Biological Source: Liquorice consists of dried,
unpeeled, roots and stolons of Glycyrrhiza glabra,
belonging to the family Leguminosae.
Phyto-constituents: The chief constituent is of
liquorice is a triterpenoid saponin known as
glycyrrhizin ( glycyrrhizic acid),which is a potassium
and calcium salt of glycyrrhizinic acid. It also
contains flavonoids, liquiritin and isoliquiritin.
Role in anti-ageing:
The anti ageing activity of liquorice is due to the
presence of phenylflavonoids (dehydroglyasperin C,
dehydroglyasperin D and isoangustone A, which are
acts as superoxide scavenger and prevent wrinkles.
JATAMANSI
Biological Source: Jatamansi consists of dried
rhizomes of Nardostachys jatamansi belonging to the
family Valerianaceae.
.Phyto-constituents: It contains volatile oil, resin,
sugar, starch and also contains jatamansic acid and
ketones, jatamansone and nardostachnone.
Role in anti-ageing:
Jatamansi triggers fibroblasts to increase the
synthesis of collagen and elastin fibres, due to which
skin elasticity increases and wrinkles formation
(ageing) decreases.
Fig.11: Jatamansi Fig.12: Arjuna
ARJUNA
Biological Source: Arjuna consists of dried stem
bark of the plant known as Terminalia arjuna,
belonging to the family Combretaceae.
.Phyto-constituents: Arjuna contains tannins,
triterpenoid saponins, arjunolic acid, arjunic acid,
arjungenin. It also contains ellagic acid, arjunine,
arjunolone.
Role in anti-ageing:
Aging occurs due to decrease in the collagen
production. Collagen synthesis and epidermal barrier
function is improved by pentacyclic triterpenoids
found in Terminalia arjuna. It also increases skin
moisturization and decreased scaliness. It strengthens
the skin barrier and induces sebum production to
reduce the signs of dry skin and protect the skin from
external challenges. It also contributes to an
improved blood circulation for better nutrient supply.
Indian Research Journal of Pharmacy and Science; Editorial; A. Chakraborty
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DI SCUSSION:
Phytochemicals derived from plants have a lot of skin
beneficial properties related to UV protection,
antioxidant action, matrix protection and skin
hydration. Over the past decade, a lot of
phytochemicals from the plant extracts have been
explored and their biological activities well-studied
in vitro. Therefore, there is a continuous requirement
for more clinical studies with emphasis on the
concentration of the ingredient in herbal products,
their formulation, safety, and the anti-ageing effect
duration.
ACKNOWLEDGEMENT:
The authors are very much thankful to the
Management of Bharat Technology for providing the
necessary facilities to carry out the study.
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conflict of interest reported: nil ; source of funding: nil
... There are four main ageing mechanisms that are listed here. [2,14] 3.1 Failure of natural selection: Natural selection has no capacity to eliminate some alleles and mutations, which may either have no beneficial effects on fitness in the early stages of development or lead to ageing. ...
... Aloe vera also provides antiviral, anti-inflammatory, and suppress the activity of collagenase, the enzyme that destroys collagen fibres, in the treatment of ageing and wrinkles. [14,17] ...
... Free radicals are destroyed by vitamin C, which scavenges them. [14] Free radical build-up in diverse tissues is linked to a variety of stress-induced situations, which accelerate the ageing process. Due to their antioxidant properties, tannins derived from E. officinalis also have a protective effect in a tardive dyskinesia rat model. ...
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... Amla (Emblica officinalis). [39]  Having the property of Neuroprotection e.g Kalonji (Nigella sativa). [40,41]  Having the property of Cardioprotection e.g. ...
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... There is a large variety of holistic and therapeutic applications of natural bioactive compounds (e.g., [6][7][8][9][10][11][12]). One of the specific targets is the bio-derived compounds with anti-aging and rejuvenation potential [13][14][15][16][17][18][19][20][21][22]. Although there exists a large number of compounds claiming such activities, the issue of their assessment is extremely complicated [1,14,23,24]. ...
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... Herbs supply nutrients necessary for healthy skin and further aid in skin functioning. These possess numerous phytoconstituents such as terpenoids, polyphenols, and carotenoids, which show anti-aging potential [76]. Sharma and Kaur investigated the anti-aging potential of SES. ...
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Natural plants and their products continue to be the major source of phytoconstituents in food and therapeutics. Scientific studies have evidenced the benefits of sesame oil and its bioactives in various health conditions. Various bioactives present in it include sesamin, sasamolin, sesaminol, and sesamol; among these, sesamol represents a major constituent. This bioactive is responsible for preventing various diseases including cancer, hepatic disorders, cardiac ailments, and neurological diseases. In the last decade, the application of sesamol in the management of various disorders has attracted the increasing interest of the research community. Owing to its prominent pharmacological activities, such as antioxidant, antiinflammatory, antineoplastic, and antimicrobial, sesamol has been explored for the above-mentioned disorders. However, despite the above-mentioned therapeutic potential, its clinical utility is mainly hindered owing to low solubility, stability, bioavailability, and rapid clearance issues. In this regard, numerous strategies have been explored to surpass these restrictions with the formulation of novel carrier platforms. This review aims to describe the various reports and summarize the different pharmacological activities of sesamol. Furthermore, one part of this review is devoted to formulating strategies to improve sesamol’s challenges. To resolve the issues such as the stability, low bioavailability, and high systemic clearance of sesamol, novel carrier systems have been developed to open a new avenue to utilize this bioactive as an efficient first-line treatment for various diseases.
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Ayurveda, Unani, Siddha, and homeopathy are natural herb-based health sciences that are being developed with a focus on India (AYUSH). In the Ayush Pharmaceutical industry, the saundarya prasad category of herbal cosmetics has a lot of space to expand. Cosmetics help to highlight and improve a person's psychological and aesthetic characteristics. The Saundarya Prasadak formulation is a cosmetic base that corresponds to known active components in Ayurvedic, Siddhanic, and Unani (ASU) medicine (references to which are easily accessible in Schedule 1st Book of the Drug and Cosmetic Act of 1940 and Rule 1945). For saundrya prasadan karma, people in the past used a variety of lepas, including Alepas, Pralepas, Udavartans, and Prakshalans, among others.One such tactic is the use of herbs. A plant or a plant extract that contains plant elements such as leaves, bark, berries, roots, gums, seeds, stems, and flowers and has a significant amount of therapeutic and dietary benefits is called a herb. It is necessary to incorporate active ingredients into cosmetics to stop skin aging and damage. Cosmetics by themselves are unable to care for the skin or other biological parts. Due to their broad usage in daily life and the lack of the usual side effects linked to synthetic goods, herbal cosmetics have become much more popular with the general public.
... Jatamansi stimulates fibroblasts to produce more collagen and elastin fibres, increasing skin elasticity and decreasing wrinkle formation (ageing) [21] Honey:Honey is a supersaturated solution derived from bees that contain proteins and amino acids, vitamins, enzymes, minerals, and other minor components. Honey is particularly useful as a wound dressing and has been used in treatments for pityriasis, tinea, seborrhea, dandruff, diaper dermatitis, psoriasis, hemorrhoids, and anal fissure. ...
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Ayurveda, Unani, Siddha, and homeopathy are natural herb-based health sciences that are being developed with a focus on India (AYUSH). In the Ayush Pharmaceutical industry, the saundarya prasad category of herbal cosmetics has a lot of space to expand. Cosmetics help to highlight and improve a person's psychological and aesthetic characteristics. The Saundarya Prasadak formulation is a cosmetic base that corresponds to known active components in Ayurvedic, Siddhanic, and Unani (ASU) medicine (references to which are easily accessible in Schedule 1st Book of the Drug and Cosmetic Act of 1940 and Rule 1945). For saundrya prasadan karma, people in the past used a variety of lepas, including Alepas, Pralepas, Udavartans, and Prakshalans, among others.One such tactic is the use of herbs. A plant or a plant extract that contains plant elements such as leaves, bark, berries, roots, gums, seeds, stems, and flowers and has a significant amount of therapeutic and dietary benefits is called a herb. It is necessary to incorporate active ingredients into cosmetics to stop skin aging and damage. Cosmetics by themselves are unable to care for the skin or other biological parts. Due to their broad usage in daily life and the lack of the usual side effects linked to synthetic goods, herbal cosmetics have become much more popular with the general public.
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Mitotic homologous recombination (HR) is an important mechanism for the repair of double-strand breakS and errors occurring during DNA replication. It is likely that the recombinational repair of DNA lesions occurs preferentially by sister chromatid exchanges that have no genetic consequences. However, most genetically detectable HR events occur between homologous DNA sequences located at allelic positions in homologous chromosomes, or between DNA repeats located at ectopic positions in either the same, homologous or heterologous chromosomes. Mitotic recombination may occur by multiple mechanisms, including double-strand break repair, synthesis-dependent strand annealing, break-induced replication and single-strand annealing. The occurrence of one recombination mechanism versus another depends on different elements, including the position of the homologous partner, the initiation event, the length of homology of the recombinant molecules and the genotype. The genetics and molecular biology of the yeast Saccharomyces cerevisiae have proved essential for the understanding of mitotic recombination mechanisms in eukaryotes. Here, we review recent genetic yeast data that contribute to our understanding of the different mechanisms of mitotic recombination and the in vivo role of the recombination proteins.
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Ultraviolet (UV) irradiation rapidly increases tyrosine phosphorylation (i.e. activates) of epidermal growth factor receptors (EGFR) in human skin. EGFR-dependent signaling pathways drive increased expression of matrix metalloproteinases, whose actions fragment collagen and elastin fibers, the primary structural protein components in skin connective tissue. Connective tissue fragmentation, which results from chronic exposure to solar UV irradiation, is a major determinant of premature skin aging (photoaging). UV irradiation generates reactive oxygen species, which readily react with conserved cysteine residues in the active site of protein-tyrosine phosphatases (PTP). We report here that EGFR activation by UV irradiation results from oxidative inhibition of receptor type PTP-κ (RPTP-κ). RPTP-κ directly counters intrinsic EGFR tyrosine kinase activity, thereby maintaining EGFR in an inactive state. Reversible, oxidative inactivation of RPTP-κ activity by UV irradiation shifts the kinase-phosphatase balance in favor of EGFR activation. These data delineate a novel mechanism of EGFR regulation and identify RPTP-κ as a key molecular target for antioxidant protection against skin aging.
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The human sebaceous gland underlies both extrinsic and intrinsic ageing. The latter is associated with morphological changes and alteration in the sebaceous gland activity. The high androgen-dependent sebum secretion in neonates falls during childhood, starts to rise again during puberty and reaches its maximum in young adults. While the number of sebaceous glands remain the same during life, sebum levels tend to decrease after menopause in females, whereas no major changes appear until the 8th decade of life in men. Reduced androgen levels in aged individuals lead to a slow cellular turnover in the sebaceous glands resulting in hyperplasia of the facial sebaceous glands in advanced age. Ultraviolet radiation and immune suppression (cyclosporine A w/o corticosteroids) represent co-factors for the development of sebaceous gland hyperplasia. Current molecular findings indicate that overexpression of the ageing associated genes Smad7 and parathormone-related protein correlate with sebaceous gland hyperplasia, whereas c-myc overexpression is associated with enhanced sebum production. On the other hand, down-regulation of the mismatch repair genes hMLH-1 and hMSH-2 may promote the development of sebaceous gland carcinoma. In addition to spontaneous single tumors, sebaceous gland carcinomas have been reported in immune-suppressed transplant recipients (azathiorpine, cisplatin, cyclosporine A) and in association with the Muir-Torre syndrome. Microsatellite instability with a loss of the mismatch repair gene hMSH-2 has been detected in immune-suppressed patients and under photo-induced DNA damage. Topical and systemic estrogens offer a treatment options for skin xerosis in menopausal females. A combination of isotretinoin and interferon-alpha seems to prevent tumor development in patients with Muir-Torre syndrome.
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The effect of chronological aging and photoaging (UV-radiation) on elastase-type enzyme activity of hairless mouse skin was studied. Aging resulted in the increase of elastase type endopeptidase activity extractable from mouse skins. Both chronic UVA and UVB radiation resulted in a significant increase of elastase type activity. PBS extracted only small part of the elastase activity, UV-A produced an increase of about 90-120% according to the type of irradiation (xenon or UV-A SUN) and UV-B produced a 72% increase. Extraction by Triton X-100 suggested that most of the activity is bound to cells and fibrous structures. EDTA inhibited 80-90% of the elastase activity in chronologically aged skin extracts and also the activity induced by UVA radiation suggesting that metallo-elastase(s) are involved. About 30% of the UVB induced activity could only be inhibited by EDTA and about 50% by PMSF suggesting that irradiation by UVB increased more serine endopeptidase activity but also MMP-activity. Chronic UVA radiation produced an increase of skin elastase activity equivalent to that observed after 24 months of aging in non-irradiated animals (approximately 100 weeks) corresponding to approximately 90% of total life span of these mice. The total increase produced by UVB was less, but the strong increase of a serine elastase, presumably from PMN-s, appear to produce a much more pronounced biological activity as shown by the presence of fibronectin degradation products in skin extracts. Such degradation products were shown to exert harmful effects on tissues. These results may well have biological significance and distinguish chronological aging and photoaging.
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Human skin, like all other organs, undergoes chronological aging. In addition, unlike other organs, skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmental damage. The primary environmental factor that causes human skin aging is UV irradiation from the sun. This sun-induced skin aging (photoaging), like chronological aging, is a cumulative process. However, unlike chronological aging, which depends on the passage of time per se, photoaging depends primarily on the degree of sun exposure and skin pigment. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. This emerging information reveals that chronological aging and photoaging share fundamental molecular pathways. These new insights regarding convergence of the molecular basis of chronological aging and photoaging provide exciting new opportunities for the development of new anti-aging therapies. This article reviews our current understanding and presents new data about the molecular pathways that mediate skin damage by UV irradiation and by the passage of time.
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Photoageing is the superposition of chronic ultraviolet (UV)-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. It is triggered by receptor-initiated signalling, mitochondrial damage, protein oxidation and telomere-based DNA damage responses. Photodamaged skin displays variable epidermal thickness, dermal elastosis, decreased/fragmented collagen, increased matrix-degrading metalloproteinases, inflammatory infiltrates and vessel ectasia. The development of cosmetically pleasing sunscreens that protect against both UVA and UVB irradiation as well as products such as tretinoin that antagonize the UV signalling pathways leading to photoageing are major steps forward in preventing and reversing photoageing. Improved understanding of the skin's innate UV protective mechanisms has also given rise to several novel treatment concepts that promise to revolutionize this field within the coming decade. Such advances should not only allow for the improved appearance of skin in middle age and beyond, but also greatly reduce the accompanying burden of skin cancer.