vladimir khavinson-epigenetic and molecular mechanisms of vitality increase
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Epigenetic and molecular Epigenetic and molecular
mechanisms of vitality increasemechanisms of vitality increase
Prof. Vladimir Khavinson
President of the International Association of
Gerontology and Geriatrics - European Region
Member of the Russian and Ukrainian
Academies of Medical Sciences
St. Petersburg Institute of Bioregulation and Gerontology
Pavlov Institute of Physiology, Russian Academy of Sciences
http://www.khavinson.ru
Potential increase in the average
human lifespan up to the specific limit
(biological reserve)
Khavinson V. Peptidergic regulation of ageing (2009)
Technologies and products for
longevity
1. Low calorie diet
2. Antioxidantes and vitamins
3. Peptide bioregulators
4. Metformin
5. Melatonin
6. Telomerase activators
7. Stem cells
Scientifically validated
Under investigation
The scheme of peptide regulation of vital activity
Harmful factors(stress, environment,
radiation, etc.)
Decreased gene
activity
Decreased protein
synthesis
Decreased organ
function
Decreased vital activity
Peptides(small proteins)
Recovery
The development of pathology and
accelerated aging
Cytomedins® - peptide bioregulators
geroprotectors (pharmaceuticals)
More than 15 million patients were treated with these pharmaceuticals both for
prevention and treatment of different pathologic states (from 1982 till 2009).
Cytogens® - synthetic peptides
(pharmaceuticals and food supplements)
Characteristic of peptides
1. Natural origin
2. High specificity
3. Complete harmlessness
4. Microdose
5. Availability production
Developed in the St. Petersburg Institute of Bioregulation and Gerontology
1. Peptide preparations (more than 30)
2. Peptide biologically active supplements (more than 40)
3. Peptide cosmetic (more than 10)
Structures of peptides
Conformations of the peptides Ala-Glu-Asp-Gly (Epitalon), Glu-Asp-Gly (Chonluten), Lys-Glu (Vilon) with optimal minimization energy. Red colour indicates oxygen molecules, blue – nitrogen molecules, black – carbon molecules, light gray - polar hydrogen molecules. Nonpolar hydrogen molecules are not displayed
Epitalon Chonluten Vilon
Basis of discoveryComplementary interaction of peptides with DNA
The formation of hydrogen bonds between nucleotides
and tetrapeptide 5’ATTTC3’-3’TAAAG5’
2,1 nm
DNA-peptide complexes
Localization of peptides in the assumed binding sites of the promoter regions of genes: A - location of Ala-Glu-Asp-Gly (Epitalon) at the site of the DNA 5'-D (GGGAAATTCCTC) -3 '(PDB: 2EZD; Huth et al. 1997); B – localization of Glu-Asp-Gly (Chonluten) at the site of the DNA 5'-D(CATGGCCATG)-3' (PDB: 1BUT; Dornberger et al. 1998); C – localization of Lys-Glu (Vilon) at the site of the DNA 5'-D(GCAGCTTCCTGC)-3' (PDB: 1QMS; Bifulco et al. 1998). Peptides molecules are depicted in the form of ball and stick, visualized by the colours of the atoms (blue – nitrogen atom, red – oxygen atom, gray –carbon atom), nonpolar hydrogen molecules are not displayed
Epitalon Chonluten Vilon
Peptide (Epitalon) and DNA
Effect of Retinal Peptides on the induction
activity of the polypotent ectoderm of
Xenopus laevis
Khavinson V. Peptidergic regulation of ageing (2009)
Effect of peptides on protein synthesis
in hepatocytes of rats of different ages
(resource increase)
Khavinson V. Neuroendocrinology Lett. (2002)
Increase in the average lifespan after
application of peptide bioregulators
Anisimov V., Khavinson V., Biogerontology (2010)
The results of 25 experiments
The death of the
control animals (0)
* - p<0.05 as compared to the control
Increase in the vital functions resources of the
organism under effect of peptide
bioregulators
Biological Activity Publications
Increase in the protein synthesis in rat hepatocytes by
42.9%
Khavinson V. Peptides and
ageing. NEL (2002)
Increase in the growth of explants in organotypic
cultures of cells of the animal by 22-42%
Khavinson V. Peptides and
ageing. NEL (2002)
Increase of the number of optional heterochromatin
in lymphocytes of the elderly people by 42.4%
Khavinson V. et al. NEL (2003)
Increase in the number of division of human
fibroblasts by 42.5% and 2.4-fold increase of the
average length of telomeres
Khavinson V. et al. Bul. Exp. Biol.
Med. (2004)
Increase in the lifespan of the animals by 20-40% and
maximal lifespan by 42.3%
Anisimov V., Khavinson V.
Biogerontology (2010), Anisimov
V. et al. Mech. Ageing Dev. (2001)
3.1-fold decrease in the frequency of tumors in
animals, induced by carcinogenic agent
Anisimov V., Khavinson V.
Biogerontology (2010)
Peptide Bioregulation
universal recovery factor of decreased protein
synthesis in a variety of pathogenic processes
and aging
Effect of peptide bioregulators on
morbidity of the employees
(40-60 years) “Avtovaz” (Tolyatti)
when exposed to harmful factors
Main group (450 employees)
received injection within 30 days
(10 injections sequentially), to improve
the functions of the brain - Cortexin,
the immune system - Thymalin,
normalization of endocrine system -
Epithalamin
Control group (400 employees)
received injections within 30 days
(10 injections sequentially)
vitamin B 12, C, D
Changes in morbidity levels
The observation period - 1 year
Control group Acute respiratory
diseases
Total
morbidity
2.4 times2.4 times
2.8 times2.8 times
Effect of peptide bioregulators on the rate of aging
the employees (40-55 years) "Tatenergo" (Kazan)
under the influence of harmful factors
Bashkireva A.S., Konovalov S.S. «Prevention of accelerated aging of working in harmful conditions». Moscow (2004)
Tested with application of bioregulators - 300 people, Control (multivitamins) - 200 people
The observation period - 1 year
* - p<0.05 as compared to the control
Effect of peptide bioregulators on
morbidity in employees (35-60
years) of OAO «Gazprom» («Oren-
burggazprom», «Nadymgazprom»)
under the influence of harmful
factors
Main group (11,192 employees)
received orally for 30 days, 6 peptide
bioregulators to improve the immune
system, brain, blood vessels, bronchus,
liver, cartilage tissue.
Control group (3,000 employees)
received orally for 30 days
multivitamins.
Changes in morbidity levels
The observation period - 1 year
Control group Acute respiratory
diseases
Total
morbidity
2.2.77 timestimes
2.2.33 timestimes
Effect of peptide bioregulators on mortality
in elderly and senile age patients
Khavinson V., Morozov V. Neuroendocrinology Lett. (2003)
Elderly
(60-74 years)
Senile age patients
(75-89 years)
Mo
rta
lity
, %
44,144,1
22,322,3
81,881,8
45,845,8
33,333,3
*
**
Observation period - 12 years Observation period - 6 years
- Control - Epithalamin - Epithalamin + Thymalin
* - р < 0.05 as compared to the control
Effect of Epithalamin on the survival of elderly
patients
IndicesControl group
(Basic treatment)
Main group
(Basic treatment
+ Epithalamin)
Number of patients 40 39
Age of patients before the
study65,1 ± 1,1 64,5 ± 0,9
Survival at 15 years 16 (40%) 26 (66,7%)*
The cause of death of
patients (myocardial
infarction or stroke (%)
83,3 46,2*
* - р < 0.05 as compared to the control
O.V. Korkushko et.al., 2011
Effect of Epithalamin on the survival of elderly
patients
* - р < 0.05 as compared to the control O.V. Korkushko et.al., 2011
Su
rviv
al
rate
(%
)
Basic therapy + complex of peptide bioregulators
Basic therapy (control)
The influence of Epiphysis Preparation
(Ephitalamin) on telomere length
Age of
patients,
years
Normal limits of
telomere length
(b.p.)
Administration of Epiphysis Preparation
Initial value After administration
5-10 13,88-15,89 ـ ـ
25-30 11,78-13,78 ـ ـ
45-50 9,67-11,68 10,53±0,97 11,97±1,32*
60-65 8,09-10,10 9,32±0,82 10,83±1,12*
75-80 6,51-8,52 ـ ـ
90-95 4,93-6,94 ـ ـ
* - p< 0,05 as compared to initial value
#Akiko Tsuji et al. Estimating age of humans based on telomere shortening // Forensic Science International. 2002, 126, 197-199.
Bekaert S. et al. Telomere Attrition as Ageing Biomarker // Anticancer Research. 2005, 25, 3011-3022.
Epiphysis Preparations
Epithalamin (Epinorm) – peptide complex with molecular weight 1000-5000 Da extracted from cattle pineal gland. The prep aration is produced in flacons (ampoules) by 10 mg for intramuscular admi nistration. Course of treatment takes 5-10 days (1 injection daily).
Epitalon –Ala-Glu-Asp-Gly tetrapeptide. The preparation is p roduced in ampoules by 100 µg for intramuscular administration. Course of treatment takes 10 days (1 injection daily).
Endoluten – peptide complex with molecular weight 1000-5000 Da extracted from cattle pineal gland. The preparation is produced in capsules by 10 mg for oral administration. Course of treatment takes 10-20 days (by 2 capsules daily).
Age, years (norm)
Investigation
Telomere length (b.p.)
Epiphysis Preparations
Epithalamin Epitalon Endoluten
60-65
(8,09-10,10)
Initial value9,32 ± 0,82
(n=25)
9,61 ± 0,93
(n=19)
9,43 ± 1,12
(n=21)
After treatment 10,83 ± 1,12 * 10,72 ± 1,21 * 10,62 ± 1,32 *
75-80
(6,51-8,52)
Initial value7,33 ± 0,81
(n=21)
7,51 ± 0,91
(n=17)
7,63 ± 0,98
(n=18)
After treatment 8,73 ± 0,78 * 8,91 ± 1,11 * 8,66 ± 1,21 *
The influence of Epiphysis Preparations on
telomere length in patients’ blood cells
* - р < 0,05 – as compared to initial value
Age, years Investigation**
6-OHMS excretion (ng/h)
Epiphysis Preparation
Epithalamin Epitalon Endoluten
60-65 Initial value
410 ± 38
(n=21)
445 ± 43
(n=19)
428 ± 47
(n=17)
After treatment 933 ± 86 * 915 ± 97 * 820 ± 92 *
75-80
Initial value363 ± 41
(n=18)
371 ± 35
(n=22)
348 ± 43
(n=21)
After treatment 690 ± 63 * 615 ± 71 * 580 ± 62 *
The influence Epiphysis Preparations on the
melatonin metabolite 6-OHMS excretion
* - р < 0,05 – as compared to initial value** - norm for people aged 30-39– 1020-1900 ng/h
Enhancement of human life sources
Application of peptide bio-regulators promoted significantly
decrease the rate of aging in humans
(40-55 years old) when exposed to harmful factors and
increase the survival rate of elderly patients (observation
period - 15 years), as evidenced by:
1. Improving physical capacity
2. Reducing the rate of aging of the cardiovascular system
3. The normalization of metabolism
4. Brain function improving
5. Increased resistance to viral diseases
«Prevention of
age-related pathology and
expanding healthy working
life»
Application of peptide bioregulators
to restore the functions of the body
Complex of the basic peptides to enhance the Complex of the basic peptides to enhance the
resource of life and prevention of ageresource of life and prevention of age--related related
disordersdisordersPinealon (brain)Pinealon (brain)
Vesugen (vessels)Vesugen (vessels)
Chrystagen(thymus)Chrystagen(thymus)
Chonluten (lungs)Chonluten (lungs)
Ovagen (liver)Ovagen (liver)
Cartalax (cartilage)Cartalax (cartilage)
The scheme:
1. Pinealon, Vesugen – 10 days
2. Chrystagen, Chonluten – 10 days
3. Ovagen, Cartalax – 10 days
Total 30 days
Health assessment is
conducted before the
application and again
after 4 months.
This is followed by mathematical processing, statistics and
recommendations. Recommended 2 courses each year.
Enhancement of life resources of
Russian Olympic team gymnasts
left to right: А. Shumilova(coach), D. Kondakova, A. Zaripova (coach),
J. Lukonina, Prof. V.Khavinson, E.Kanaeva, V. Schtelbaums (coach),
I. Viner (honored coach of Russia), О. Buyanova (coach), D. Dmitrieva
Peptide application
areas
Domestic animals
Domestic animals
Synthetic preparations
Synthetic preparations SyntheticSynthetic Medical
cosmetologyMedical
cosmetology AvicultureAvicultureSportsmen products
Sportsmen products
Natural preparations
Natural preparations NaturalNatural Preventive
cosmetologyPreventive
cosmetologyAnimal
husbandryAnimal
husbandry
Functional foods and beverages
Functional foods and beverages
PreparationsPreparationsBiologically
active supplements
Biologically active
supplementsCosmetologyCosmetology Veterinary
scienceVeterinary
science NutritionNutrition
CONCLUSION
As a result of 35 years of investigations was discovered a
new group of peptides – signaling molecules, which
epigenetically regulate gene expression and protein
synthesis. This promotes the enhancement of human life
resources and extending working life.
The institutions, where the basic studies were
conducted (35 years)
St. Petersburg Military Medical Academy
(1977-1991), Head - member of the Russian Academy of Medical Sciences
Prof. V. Khavinson
St. Petersburg Institute of Bioregulation and Gerontology
(1992-2012), Head - member of the Russian and Ukrainian Academies of Medical
Sciences
Prof. V. Khavinson
Petrov Oncology Research Institute
(1977-2012), Head - member of the Russian Academy of Sciences
Prof. V. Anisimov
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University
(2008-2012), Head – member of the Russian Academy of Sciences
Prof. B. Vanyushin
Gerontology Institute of the National Academy of Medical Sciences of Ukraine
(1992-2012), Head – Academician of the Academy of Medical Sciences of Ukraine
Prof. O. Korkushko
Foreign institutions where some of the studies
were conducted
National Institute on Aging (Baltimore, USA)
Italian National Research Center on Aging (Ancona, Italy)
Institute of Anatomy, Ludwig-Maximilians-University of Munich
(Munich, Germany)
Prince Felipe Research Center (Valencia, Spain)
University of Antwerp, Department of Biomedical Sciences (Antwerp, Belgium)
Prof. Vladimir Khavinson and staff of the Laboratory of Biogerontology
of the St. Petersburg Institute of Bioregulation and Gerontology
THANK YOU
FOR YOUR
ATTENTION !