AGING AND BIOTECNOOGY · Researches discovered with mutation in genes daf-2 or age-1 lifespan...
Transcript of AGING AND BIOTECNOOGY · Researches discovered with mutation in genes daf-2 or age-1 lifespan...
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AGING-BIOTECHNOLOGY RELATIONSHIP
Presented by: Nahid Qorbanzadeh
Under supervision of Dr. Ahmadpour
Qazvin university of medical science
2 5/29/2016
CONTENTS Introduction
History
Aginge:effective factors
Biotechnology role in aging
conclusion
References
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Introduction (9)
Aging is natural process
Senescent cells replaced with juvenile
Senescence appear in different level of tissue ,organ, cell and
molecule
Senescence , derived from senex
meaning ”old man”
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Introduction(9)
There is various agent like DNA damage,
oxidative demolition ,Telomerase activity and
metabolical flow can accelerate aging process
Anti-aging medicine goal depend on health
span by interference in this pathways
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History (9)
Three hypothesis about aging event
I. accumulation hypothesis (by Medawar)in1952
II. Antagonistic pleotropic hypothesis
I. Somatic transmitters(by Kirkwood)in1996
Anti- aging medicine got current after 2000
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Main effective factors in cell senescence (9)
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AGING
DNA damage,
repair and mutagenesis
Free radicals &
aging Signal transduction
Metabolic flow
Age-related disease
Cancer,
Rheumatoid
Arthritis,etc
Genetic
context or
gerantogen
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DNA damage (3)
..
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Genetic context (5)
Aging and longevity are controlled by genome
Aging can be suppressed and life span increased
organisms with low half life like nematode caenorabditis elegans are
used in gerantogens study
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Genetic context , metabolic follow & signal transduction
Insulin/insulin-like growth factor pathway with influence on lifespan
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Researches discovered with mutation in genes daf-2 or age-1 lifespan increase
The orthologs gene mammalian respectively
InR and PI3K
DAF-16 human orthologs is FOXO
Age-1
DAF-16 Increase lifespan
Daf-2
longevity
gene
Age-1 or daf-2 and their orthologs are suitable
target for RNAi
(5) 12 Aging and biotechnology relationship
How free radicals cause aging
13 Aging and biotechnology relationship http://www.mdpi.com/1420-3049/21/2/163
Any one of them have some pharmaceutical target
Biotechnology role in aging(9)
Detection, decrease of aging process
and increase of health longevity
Creation of aging process and death in
malignant, cancerous and infection cells
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(9)
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oxidants
Inhibitors and Inducers of
Apoptosis proteins
Gerantogen activity
Telomerase activity
Mitochondrial protein and
Membrane potential
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For accomplish the above cases biotechnology Needs some techniques
such as:
• RNAi (siRNA & miRNA)
• Drug delivery techniques materials Nano
• Cell therapy, Gene therapy
• Tissue engineering
• Recombinant antibody
• DNA vaccines
(9)
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RNAi-based therapeutic (6)
The induction of RNAi relies on small silencing RNA
affect specific messenger RNA(mRNA)degradation
siRNA and miRNA have central function in RNAi technology
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RNAi-based therapeutic
SiRNA target genes disease
HIV-Tat, HIV-Rev, HIV-Vif
HPV-E6 & E7, HBV-S1,-S2,-S-X
CCR5, CXCR4 ,CD4
Viral
P53 mutant, k-Ras, BCR- ABL, MDR1
C-Raf, Bcl2, VEGF, PKC-a, B-catenin
Cancer
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two RNAi delivery strategies to target cancerous and viral
Tissues;(6)
I. Systemic administration
II. Local administration
Local administration may be promising to overcome
systemic delivery disadvantage such as
Liver toxicity and stimulation of immune response
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RNAi-based therapeutic(6)
Oncology can benefit the most from this novel therapeutic strategy
Lung cancer is the most common cause of cancer-related death worldwide
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modified siRNA platform (6)
E.g.: PnKRNA(proline naked RNA) and nkRNA(naked RNA)
With local delivery through inhalation
More resistant to degradation because of their unique helical structure
Without inflammatory response in Intrapulmonary delivery
Lung and ayes, few organs successful
RNAi could be delivery of naked siRNA
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Novel platform SiRNA (8)
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P-GP-mediated drug resistance (7)
P-glicoprotein pomp(p-gp) a member of ABC –transporter family
Cause drug resistance in some age-related disease
Such as rheumatoid arthritis(RA) and alzymer
p-gp an excellent target to control these disease
TNF-a as a biological target for RA treatment
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Relevance of p-Gp in drug resistance(RA) (7)
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Apoptosis-targeted therapies (2)
Apoptosis, programed cell death (PCD) maintains healthy ,survival/
death balance in metazoan cell
Defect PCD cause cancer or autoimmunity
enhanced PCD cause degenerative disease, immunodeficiency, infertility
Inhibitor of apoptotic proteins (IAP) and FLICE-inhibitor protein (cFLIP),
central control point of PCD pathways, modulate by carcinogenesis signals
cFLICE ; cellular FADD –like interleukin-1beta converting enzyme
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28 Aging and biotechnology relationship http://www.hindawi.com/journals/bmri/2014/616149/fig1/
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Apoptosis-targeted therapies (2)
successful nonsurgical cancer cell eradication approached
by induction of apoptosis
apoptotic-based therapy is focused onBCL-2 family proteins
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Thre
e st
rate
gie
s to
over
com
e cy
top
roac
tiv
e ef
fect
of
BC
L-2
Shutting off gene transcription
Inducing mRNA degradation by antisense
oligonucleotides
Directly attacking the proteins with small
molecular drugs
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.
Some anti apoptotic drug in cancer therapy (2)
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Targeted
molecule
Modulatory
function
drug cancer
Steroid/Rtinoide
transcription
factor(RAR,VDR
Inhibit BCL-2 doxorubicin Breast cancer
Interaction with DNA
Lower serum
PSA
Traglitazone (As a PPRA
agonist)
Prostate cancer
Histone
deasetilase
Inhibit BCL-2,
BCL-xL
HDAC
inhibitors
Some tumors
BCL-2, BCL-
xL
Inhibit BCL-2,
MCL
Synthetic BH3
peptide
Follicular
lymphoma
Bak and BaX Activate Bak
and BaX
Synthetic BH3
peptide
-
CD20 Complement
activation
Monoclonal
antibody
Certain
leukemia
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Telomerase-based therapies(4)
Telomeres are guanine-rich repeated sequences
located at the end of chromosomes
A number of protein are located on telomeres witch
protect telomeres by forming D-and T-loops
They function as a biological clock limiting the cell proliferation
with every next cell division that accompanied by cell senescence,
mitotic crisis and apoptosis
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Telomerase –based therapies (4)
most cancer cells(~85%) reveal telomere length maintaince that
is responsible for telomeres renewal during cell proliferation
cancer cells utilize telomerase for this purpose
the enzyme is a multisubunit rebonucleoprotein contains
catalytic subunit and RNA molecule as a template for
telomerase revers transcription(TERT)
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Telomerase-based therapies (4)
There is several strategies for control telomerase in cancer cells
Antisense technology against telomerase RNA component(TR)
and telomerase revers transcriptase
Ribozyme against TERT
Modulation of interaction with other proteins involved in the regulation
of telomerase and telomeres
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Transcriptional mechanism of telomerase regulation (4)
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Telomerase-based therapies (4)
Natural-derived compounds with antitumor activity in the context
of telomerase regulation in breast cancer
butein(3,4,2’,4’-tetrahydroxy chalcone)
it cause dowregulation by suppression of TERT gene expression
in a C-myc depending manner
pectenotxin-2 dependent attenuation of TERT expression was
mediated through suppression of C-myc and sp1-binding on the
regulatory region of TERT
C-myc have role in TERT gene expression induction
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Telomerase-based therapies (4)
silencing TERT and HER-2 (human epithelial grow factor-2)
by SiRNA technology increased radiosensivity and down
regulation TERT/telomerase
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Recent natural anti-aging compounds (1)
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Compound name source application
Grape-seed extract
Fruit polyphenols&
flavonoids
Skin treatment
Jojoba protein Jojoba plant Moisturizer& anti-
wrinkle
Ferulic acid Plant phenolic
compounds
Anti-oxidant & anti-
inflammatory
Berries - Cancer & improve brain function
Extra virgin olive oil olive Reduce aging, cancer
& cardiovascular
diseases
lycopene tomato Reduce cancer &
aging risk
Spirulia plankton Immune-stimulator &
moisturizer
Dark chocolates Cocoa bean Reduce skin
inflammatory
Kojic acid dipalmitate Japanese mushroom Invigorating & skin
lightening
Nano biotechnology effect in increasing longevity
- advance in joint -artificial organs -development of -local drug
displacement -in vivo sensors cell-material delivery
-noninvasive & -local drug interaction -gene therapy
invasive diagnosis delivery -tissue scaffold expansion
to fast disease follow - nerves engineering -foppish structures
up stimulation -Genetical -fast diagnostic
- co-diagnostic -heart materials & treatment of cell approaches
devices cordial disease senescence
-cancer wise treatment treatment - treatment by
stem cells
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Conclusion
Although aging is gradual and spontaneous changes in structure and function of living creature with time passing
Some disease such as cardiovascular , cancer and accidents
are the main cause of death and early aging
Up to now the disease treatment were based on chemotherapy
drugs, different rays and surgery
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conclusion
Nowadays with use of medical biotechnology and related field to be
able to Take a little step in order to have a health senescence cycle by;
Early diagnosis of disease, follow up treatment and recovery
Efficient delivery of drug to target point, make organ and different
biochemical sensors
Genetical drugs based on RNA and DNA with attention to patient
genetical features
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References
1) Khare N, Khare P, Yadav G. Recent Advances in Anti-Aging–A Review. Global
Journal of Pharmacology. 2015;9(3):267-71
2) Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular
targeting therapy in cancer. BioMed research international. 2014;2014.
3) Nicolai s, Rossi A, Di Daniele N, Melino G, Annicchiarico-Petruzzelli M, Raschellà
G. DNA repair and aging: the impact of the p53 family. Aging. 2015;7(12):1,050-
1,65.
4)Holysz H, Lipinska N, Paszel-Jaworska A, Rubis B. Telomerase as a useful
target in cancer fighting—the breast cancer case Tumor Biology.
2013;34(3):1371-80.
5).Lapierre LR, Hansen M. Lessons from C. elegans: signaling pathways for longevity.
Trends in Endocrinology & Metabolism. 2012;23(12):637-44
6)Fujita Y, Kuwano K, Ochiya T. Development of small RNA delivery systems for lung
cancer therapy. International journal of molecular sciences. 2015;16(3):5254-70.
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References
7.) Tsujimura S, Tanaka Y. Disease control by regulation of P-glycoprotein on
lymphocytes in patients with rheumatoid arthritis. World journal of experimental
medicine. 2015;5(4):225.
8). Hamasaki T, Suzuki H, Shirohzu H, Matsumoto T, D'Alessandro-Gabazza CN, Gil-
Bernabe P, et al.e42655:(8) Efficacy of a novel class of RNA interference therapeutic
agents. PLoS One. 2012;7
-7(:4)1;2011. مولكولي-مجله تازه هاي بیوتكنولوژي سلولي. پیری سلولی و بیوتکنولوژی. یاری ).9
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