Professional Documents
Culture Documents
AGING
SCIENCE
AGAINST
Project background
Dear Colleagues!
The value of a long and healthy life is obvious to every reasonable person. Therefore, aging is a
serious and until now unsolved problem. Slowly but inexorably, aging decreases the quality of life,
makes people weak and powerless, prevents the realization of people’s aspirations. Sooner or later, it
leads to death.
The problem of aging has become relevant in politics. Demographers warn that in the coming
decades aging population and decreased birthrates will place a heavy burden on social security and
pension systems in all developed countries. The remaining workforce may become unable to support
the growing number of retirees.
Leading gerontologists from 10 countries declared in an open letter that aging can be slowed down
and healthy life can be prolonged. We share the view that the problem of aging can be solved in the
next few decades and that humankind already has everything necessary.
1. Our society has financial resources for solving this problem —
The problem of aging can a major project to defeat aging would cost only about 30 billion dollars.
be solved in the next few 2. A large body of knowledge about aging has been accumulated that
decades is being used to create a unified system model of human aging.
3. Powerful new technologies in genomics, drug design, mathematical
modeling and other fields make it increasingly possible to control and
direct processes inside the human body.
4. Many promising ideas and aging hypothesis that can help solve the
remaining problems have been developed.
Unfortunately, these opportunities are not being fully used, the efforts of researchers are largely
uncoordinated, science and society do not have a clear overarching goal – to defeat aging.
To join the efforts of individual scientists, research and health institutions, non-government and political
organizations at international coordinating center of the program is needed. It’s primary tasks are:
1. attracting renowned experts in life sciences and research management to
Separate projects the project
should be joined within 2. creating a scientific and organizational program
an integrated scientific 3. developing a plan to implement this program
framework 4. promoting this program in social, business, and political circles.
Clearly, to create a comprehensive research program to defeat aging (and to carry out the research) many
organizations from different countries need to act together for the project to be finished in reasonable
time. Such program should be created and implemented with broad international support of scientists,
politicians, businessmen, and society.
We note that most of the program should be organizational and managerial in nature. Its successful
realization will consolidate scientists from different countries, consolidate and commercialize
intermediate research results, paving the way for attracting large-scale government and international
funding.
We ask scientists and managers to share their knowledge and experience in creating collaborations,
organizing research and using expert knowledge, lobbying and managing large projects.
Contact details:
“Science for Life Extension” foundation,
Leninsky pr. 15, 119071, Moscow, Russia.
+7 495 748-69-37
longevity.foundation@gmail.com
anti.starenie@gmail.com
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Project
Elimination of aging
planning will lead to
Grants
A promise
of future funding
will give
will develop
for developing
A core group
describes of scientisits
3 subsequent
work
Grants
Overall plan
will help
attract will give
Science foundations
will participate science and health govt
Project strategy in developing Project implementation stages
departments
Iterations of the
1 will form the basis of scientific program,
will be presented to will be
presented to from basic to final
Market report (key aspects will form
ones.
of fight against aging) a part of
Funding stages.
Description of Project participants.
will provide Experts on fighting «Modern understnading
will find source information for of aging»
against aging Project planning.
materials for
inclusion in
will find Major project
will prepare
milestones are listed
Key scientists with below and marked
Planning group will pick integrated approach with numbers on the
diagram.
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The development of the program involves the following stages (deliverables marked in
bold):
Report on AGING SOCIETY
1. Writing an industry report (a report on key aspects of fight against aging). key aspects Biological causes Tools
2. Developing the project strategy.
of fight
influence
History of aging to control aging
3. Creating a detailed implementation plan. (modern understanding of aging) (science and medicine)
Psychological
Educational programs
in biology of aging
4. Developing a scientific program to eliminate aging. againstg describes attempts
allow to control form
aspects Cultural background
aging
aging influence
influences
allow to change
The program to eliminate aging should be promoted and lobbied for in national
governments, to international organizations, among private sponsors and investors.
(industry report)
Aging
in all its complexity Potential
The concept map of the report. participants Prevailing attitude Communciation methods
The first step in our project is to write a review of key aspects of fight against aging (a Large blocks contain major affects us
market report) so that potential partners, experts, sponsors and everyone else could areas described by the report. through
see the overall picture of the struggle to defeat aging. Smaller blocks represent the defines the
position of
main elements of the diagram include
and their connections show real Ethical, humanitarian and Demographics,
We invite you to join now the discussion about ways and means to combat aging
connections. philosophical impact epydemiology and
organized by our foundation, while this review is being prepared and later during the of aging economics of aging
Society
project planning. Describe your vision of the scientific program, help excite the society
about research into mechanisms of aging, share your experience in relevant fields. We
are always open to co-operation and are glad to get in touch with you!
to be eliminated
needs
influences
against aging
Right now the foundation project team works on ONGOING EFFORTS PROJECTS Government
the first major deliverable – a report about the This document will provide
fighting against aging field. This document will participants with basic Coordination Knowledge management
shed some light on a very uncertain area and knowledge about the field Champions
of distributed groups
will provide participants with basic knowledge we work in creates Government Fight against aging
about this topic. Once it’s completed, participants, on the agenda
supports
experts, journalists, politicians and the public will form work on
be able to get a comprehensive understanding of
provides can be achieved by
all aspects related to aging that are important for
project success.
Creating roadmaps
Organizations
Lobbying
We call for directors of science organizations, lobbyists, sociologists, public relations Commercial projects Funding for fight against aging
specialists, financiers, methodologists and all professionals interested in fighting aging paves the way for
to provide any possible assistance to the project. The first round of consultations with start
for helps start
experts is under way. This includes individual interviews with experts and work sessions
with several (3-5) specialists. During the sessions additional questions to explore
are formulated, while the information gathered is included in the report. As a result Projects & programs can be Large scientific Can be State programs
integrated into projects turned into and projects
knowledge needed for fighting aging becomes available to everyone.
such as our
describes how to
organize “Science against aging”
4 I I 5
Understanding aging and the Life, aging and death processes in humans. Intervention possibilities
development of science program
The report section describing modern understanding of aging has significant
importance on its own. In this section we will present a coherent description of aging fixes Genetic engineering
Epi[genome]
process, its nature and characteristics of human aging. The content will be based on
presently available scientific knowledge about aging.
Healthy lifestyle changes Environment defines
No such description is available yet. Both scientific works on gerontology and impact
popular articles rarely do more than list hypotheses about causes of aging. The
information is poorly structured and doesn’t form a coherent system.
Metabolism intervenes with Prophylactics Preventative
Modeling helps understand and regulation includes
We plan to work in close contact with leading experts on systems approach to study of aging medicine
of aging. We will collect information about key processes that comprise human aging replaces
and combine it into a single system illustrated on a single diagram. The level of detail causes as a prevents and fixes
will be determined by practical considerations – we plan to make a general outline Gerontology studies side-effect
before going into details of individual processes. This diagram will show “white
spots” that call for further studies and opportunities for interventions in the aging
process. Nanomedicine removes Damage and tries to completely Engineering uses
regulation errors remove and control approach
In this section we will highlight key aspects
The “modern understanding of aging, such as its evolutionary nature, the includes
of aging” diagram will make existence of specific mechanisms of aging, causes
removes Rejuvenation
it possible to communicate specificity of aging by tissue and organ types and
our vision of the project others.
Age-dependent Age-independent
complicate pathologies
Aging: a system of life, aging and death pathologies
processes in human organism and possible treats
interventions (overall view).
causes treats Geriatrics includes Medicine
This description will make it possible to communicate our vision of the project to
our partners and experts. It will also help attract potential new participants in the
project. Artificial organs Frailty (decreased
(grown and replace Failing organs functionality) reverses
manufactured)
In addition this description will serve as a starting point for development of the
compensates for
scientific program to eliminate aging. After outlining the modern understanding
lead to
of aging we will start work on a roadmap (a concept of the program outlining key
directions for research) to elimination of aging. The roadmap will be expanded and
finalized at an interactive scientific conference in a “Dahlem conference” format Life support systems
(very effective Dahlem Konferenzen workshops were held in the Free University Body means the
Biological death Decreasing attempt to
Social measures
and anabiosis maintains death of quality of life compensate for
of Berlin since 1974). Participants at such conference will do more than just give technologies
presentations, during a whole week they will work in groups on a section of the contains
roadmap. Problem
Brain concludes with
The roadmap will be expanded with information about specific research projects
and other information. The resulting document will contain the “scientific program contains Possible
intervention
to eliminate aging”. We will then lobby for it to be accepted and funded. Large scale Neuromodeling
including modeling means the
preserves Personality death of Information death
research project will thus be initiated, culminating in the development of methods of the brain The full “modern understanding of aging” diagram will contain Entity
and tools to first slow and then completely eliminate human aging. several hundred times as much detail as this illustration with
additional detailed descriptions.
Today we want to offer one approach to developing the program to cure aging for Science
discussion, comments and criticism. This approach has been developed by a group
of Russian researchers for “Science for life Extension” foundation.
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We propose for discussion, amendment and supplement an approach to the
structure Proposal of the
Individual proposals regarding this section are
development of the “Science against Aging” program set forth by Russian published in a booklet on the page specified.
scientists. Upon completion of the development of all program sections, materials This section requires elaboration.
will be structured according to this suggested pattern. “Science agai nst aging” program ? Reserved sections for the further development of
the program.
Research related to
Systematization of knowledge Development and improvement of contemporary methods, Statement of fundamental
Research in the comparative Study of aging processes and stress resistance at various fundamentally new
in the biology of aging and approaches and technologies for the study problems in the biology
biology of aging levels of organization of biosystems interventions into the aging
longevity in humans and slowdown of aging processes of aging
processes
? ? ? ? ?
? Identification of molecular
markers of aging 55
What other questions may be crucial for
understanding the mechanisms of aging?
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PROGRAM AIMS
AND OBJECTIVES
Main Aim
Development and application of scientific methods in order to
substantially extend human healthy lifespan
Priority Objectives:
• Research in fundamental mechanisms of aging
• Development of methods for intervention in the aging process
in order to slow it down
• Practical application of the scientific findings in order to
substantially extend human healthy lifespan
Step-by-Step actions
1. Drawing up a complex interdisciplinary proposal for research
into aging mechanisms
2. Defining the essential forms and means of international
cooperation for the implementation of the proposal
3. Defining the essential forms and means of international
cooperation for the implementation of the proposal
4. Concluding an international agreement about cooperation on
research into aging
5. Implementing the plan and achieving its priority objectives
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TABLE OF CONTENTS
Section 1.
Fundamental mechanisms
of aging......................................... 14
Section 2.
Genetics of longevity
p r o g ram and aging...................................... 19
Section 3.
Science
Metabolic aspects of aging
and longevity................................. 26
Section 4.
Immunity and aging..................... 30
against
Section 5.
Stem cells and aging.................... 35
Section 6.
Application of stem cells in
aging
geriatrics and gerontology........... 39
Section 7.
Medicated geroprotection............ 46
Section 8.
Geroprotector Efficacy Study....... 51
Section 9.
Identification of molecular
markers of aging.......................... 54
SE l e c t e d P RO P OSALS
Section 10.
Mathematical modeling of
Russian scientists have elaborated a number of proposals on lifespan, longevity and aging........ 57
several sections of «Science Against Aging» program.
Section 11.
We would appreciate if you could take part in development of these Microecology and aging............... 63
sections or contribute to working out new ones.
Section 12.
Interconnection of aging and
reproduction................................. 65
Section 13.
Environmental effect on aging
processes...................................... 66
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Aging Fundamental mechanisms of aging Maps of these biological dependencies will be further
developed while the program “Science against aging” is
Point Non-homologous Telomere shortening, Transposition of mobile DNA demethylation Stalled replication forks Non-functional
mutations recombination T-loop loss genetic elements Protein aggregates proteins Proteosomal Autophagy
degradation of protein of damaged
Subcellular aggregates mitochondria
Micronuclear Chromosomal Alteration in the gene Stress response Defective mitochond- Proteosome Lypofuscin Autophagy
formation aberrations expression pattern genes induction rion accumulation inhibition accumulation inhibition
Mitotic Cell senescence Temporary cell cycle arrest, allowing Apoptosis Compensatory proliferation Metabolic shift towards Damages segregation
catastrophe (replicative Apoptosis Energy supply failure Cellular for efficient DNA damage repair (for proliferating cells) of stem cells energy storage during cell division
and stress induced)
Disturbance in neuroendocrine Impaired Organ systems Neuroendocrine system Feedback system which
regulation homeostasis Oncogenesis Immunity decrease regulates homeostasis
Oxygenation Diet Chemical mutagens Ionizing radiation UVB radiation Light regime Temperature Persistent Hormesis (stimulatory action of Optimal
conditions infections Ecological moderate doses of stressors) environmental conditions
Psychological
stress Psychologic Optimism Healthy life-style
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Section 1
compare their gene expression with various
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1.1. RESEARCH ON DIFFERENT 1.1.1.5.2. Characterization of
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1.1.2.1.3. Homoplasmia of damaged 1.1.3. CELLULAR-TISSUE LEVEL
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1.1.3.4. Cytodifferentiation and 1.1.3.8. Study of resistance to environmental
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1.1.4.2.3. Proneness to tumorigenesis
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Section 2
is to select a substance (future drugs) which
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2.1. IDENTIFYING GENES 2.1.3.1.12. Emydoidea blandingii
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2.2 ANALYSIS OF THE EVOLUTION- 2.2.5. Oncosupressors and apoptosis
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2.3.4. Differentiated cells nucleus 2.4.1.3. Antioxidants:
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2.5.2.1. Reveal latent aging stages, preceding histone modification, regulation of
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analysis of frequency dynamics for 2.6.4.1. Experimental development of
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gene and aging gene expression with
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Section 3
consumption are adaptive mechanisms
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3.1. MAIN AREAS OF RESEARCH process of aging, its connection with
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3.1.4.1. Research of glucose and fatty acid 3.2.2.2. Living conditions;
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3.3.3.1. Metabolic characteristics in women in
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Section 4 4.1. Fundamental
investigations of the
immune system during aging
Immunity 4.1.1. Investigation of interaction between
and aging aging and function of the immune
system organs.
4.1.1.1. Investigation of age-related changes
in the central and peripheral
immunogenic organs:
4.1.1.1.1. Investigation of age-related
changes in the central immunogenic
MAIN RESEARCH DIRECTIONS organs:
4.1.1.1.1.1. Investigation of the
mechanisms of age-related
In old age, diseases increase the immune thymus involution,
deficiency which is typical for elderly people.
4.1.1.1.1.2. Investigation of the role of
It is quite possible to delay aging and abate
peptide bioregulators of the
manifestations of old age by preventing the
«cytomedine» class generated
weakening of normal immunity functions.
by hypophysis and epiphysis in
controlling the thymus activity
Main goals of aging study
4.1.1.1.1.3. Investigation of bone marrow
• Detection of fundamental ways of age- as the primary organ of the
related changes in the central and peripheral immune system including
organs of immunogenesis. the reasons for decrease in
the number of stem cells and
• Development of new evaluation standards of disorder of their differentiation.
genetic and immunological status influencing
the aging rate. 4.1.1.1.2. Investigation of age-
related changes in the peripheral or
• The study of the character of immune secondary immunogenic organs:
response toward various antigenes of narrow
4.1.1.1.2.1. lymph nodes;
specificity of inbred and congenic mice lines
to understand the interrelations between the 4.1.1.1.2.2. spleen;
strength of genetic immunity force lifespan. 4.1.1.1.2.3. the system of lymphoepithelial
masses in mucous tunic of
• Determination of the influential mechanisms
different organs.
of endogenous (autoimmune diseases, cells
mutations) and external causes to immune 4.1.1.1.3. Investigation of
system and the adding rate (chemical, interconnection between the
industrial pollutants, uncontrollable central and peripheral organs of
pharmacalogical drugs, hypodynamia, immunogenesis in the course of
psycho-emotional stress, the influence of aging.
electromagnetic radiation). 4.1.1.1.4. investigation of age-related
• Creation of methods for the immune changes in immune privileged organs
correction of age-related changes and slowing and tissues:
of the aging process. 4.1.1.1.4.1. CNS,
• Determination of mechanisms preventing 4.1.1.1.4.2. testicles,
mutational stream in the course of individual 4.1.1.1.4.3. eyes,
development. Radical longevity increase 4.1.1.1.4.4. thymus parenchyma.
is impossible without understanding
immunological control mechanisms.
4.1.2. Investigation of cell immunity as the
main factor of body protection against
viruses, pathogenic fungi, intracellular
bacteria, tumors.
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4.1.2.1. Study of innate immunity: generation of pro– and anti-
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aging process. 4.1.4.1. Study of individual reactivity to
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4.1.5.2. Search for typical immunity disorders 4.2.2. Reconstruction of the body immune
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4.3. Intrathymic selection administration of tree-structured
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Section 5
5.1. STUDY OF STEM CELLS AND
Stem cells THEIR SPECIFIC NICHES
“AGING” AS A PROCCESS OF
and aging LOSS OF THE ORGANISM’S
REGENERATION POTENTIAL
AND MANIFESTATION OF THE
AGING PHENOTYPE
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5.1.4. Study of the effect of niche cells 5.2.2. Development of methods of collection,
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5.4.1.3. Carrying out of clinical studies of 5.5.1.1. In regulation of telomeres length
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for coupling during transplantations
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Section 6
Therefore, only joint efforts of specialists in
APPLICATION OF STEM different disciplines within a mainframe of the
Program could ensure an effective application
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6.1. STUDIES OF BASIC MECHANISMS 6.1.2.3.1. Identification of the genes
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6.2. STEM CELL-BASED CELL 6.2.2.4.2. Diseases caused by a
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6.3.3.3. Modification of SCs and their 6.3.5.1. Studies in the field of direct
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6.4.3.2.1 Fetal bovine serum/fetal calf 6.4.6.3. Establishment of the strict control
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6.4.8.2. Establishment of the specific set of utilizing “artificial tissue” (e.g., bone
44 I
cell expansion, storage and shipping);
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Section 7 to be highly efficient in preventing
age-related human pathologies.
Medicated Develop mathematical methods of
experiments planning and results
Geroprotection analysis, including proper methods
of small samplings processing.
7.1.7. Study if there is a physiologic
necessity to keep aged cells in
tissues.
7.1.8. Study of the possibility of
MAIN RESEARCH DIRECTIONS modulation of cytokines secretion
by aged cells.
7.1.9. Develop a drug that will inhibit
The main objective is to create a method for synthesis of pro-tumor cytokines by
the selection of medication combinations aged cells or induce removal of such
(based on individual genetics, age, health cells from tissues.
status, lifestyle etc.), which would inhibit as
much as possible (preferably – completely) 7.1.10. Analyze the possibility to activate
the manifestation of physiologic aging. DNA repair system as a gero-
protection factor.
7.1.11. Analyze the possibility to activate
7.1. GENERAL inducible endogenous antioxidant
GEROPROTECTION systems (in particular, internal
mitochondrial systems) as a
RESEARCH ISSUES geroprotection factor.
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7.2. RESEARCH a possible target for epithalon and
Medicated Geroprotection
OF Geroprotective epithalamin drugs.
PROPERTIES 7.3.2.4. Study epithalon and epithalamin
OF MELATONIN effects on adrenergic mediators
metabolism in CNS and epiphysis
7.2.1. Continue research of melatonin’s sensitivity to noradrenergic
effect on cells transformation, stimulation.
oncogenes expression, apoptosis and
senescence processes. 7.3.3. Research of geroprotective
properties of vilone, thymalin and
7.2.2. Study melatonin’s regulative effect on thymogen.
mediators and peptides interchange
in CNS. 7.3.3.1. Continue research of effects of vilone,
thymalin and thymogen on genes
7.2.3. Study melatonin’s effect on expression mechanism.
hormones secretion (primarily by
APUD-system). 7.3.3.2. Decipher specific molecular
mechanism action of vilone,
7.2.4. Study melatonin’s effect on thymalin and thymogen
telomerase expression and telomere on the target genes, establish
length. mediators of these processes
in order to synthesize
7.2.5. Study the impact on free radicals more effective equivalents
production in mitochondria and their of these peptides.
afterlife in the cell.
7.3.4. Research of mechanism of action of
7.2.6. Study extra-epiphysial melatonin’s deltaran:
role in the organism.
7.3.4.1. Study the effects of deltaran on
oxidative processes in the body.
7.3. RESEARCH
OF Geroprotective 7.3.4.2. Study the effect of deltaran
on the various mechanisms of
PROPERTIES cancerogenesis, including oncogene
OF PEPTIDES expression, age-dependant
accumulation of senescent cells and
7.3.1. Continuation of analysis of fractions their ability to release pro-tumoral
peptide extracts of thymus and humoral factors.
epiphysis extracted by different
methods, research of their 7.3.5. Study the role of synthesis induction
geroprotective activity. of antioxidative ferments and
melatonin in geroprotective effects of
7.3.2. Research of geroprotective peptide drugs of epyphysis.
properties of epithalon and
epithalamin: 7.3.6. Experimental and clinic research
of known and newly synthesized
7.3.2.1. Continue research of epithalon peptide drugs on the model of
and epithalamin effect on genes human geriatric disease (diabetes,
expression mechanisms. atherosclerosis, hypertonia and
7.3.2.2. Decrypt specific molecular others) in laboratory animals.
mechanism of epithalon and
epithalamin effect on target genes,
determine mediators of these
7.4. RESEARCH
processes in order to synthesize OF GEROPROTECTIVE
more effective equivalent of these PROPERTIES
peptides. OF GROWTH HORMONE
7.3.2.3. Study epiphysis peptides effect on the
performance of APUD system (single 7.4.1. Find out possibility for increase on
hormone producing cells system) as aging by effect on IGF-1 receptors.
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7.4.2. Develop antagonist of IGF-1 7.7. STUDY OF Geroprotective
Medicated Geroprotection
receptors. PROPERTIES
OF ANTIOXIDANTS
7.5 FULL RESEARCH OF
Geroprotective 7.7.1. Study their effect on carcinogenesis
PROPERTIES OF THE caused by different agents; study
their synergetic and antagonistic
FOLLOWING Drugs, qualities to other drugs of this group
INCLUDING ANALYSIS OF and geroprotectors with a different
PATHO-MORPHOLOGICAL mechanism of action.
CHANGES IN LABORATORY
7.7.2. Comparative research in vivo and
ANIMALS: in vitro of anti-oxidants’ effects on
the mechanisms of apoptosis and
7.5.1. Thyroxin. cellular aging.
7.5.2. Cross-linking blocker (EDTA,
β-aminoproprionitrile, carnosine and 7.7.3. Comparative research in vivo
L-acetylcarnosine, ALT711 (algebrium and in vitro of antioxidants’
is a cross-linker destroyer)). effects on cell differentiation
process and production of cytokines
7.5.3. Adaptogens (extract of Redberry, by them.
Eleuterococus, Ginkgo Biloba).
7.7.4. Comparative research in vivo and in
7.5.4. Fullerenes and their derivatives as vitro of antioxidants’ effects on the
antioxidants. synthesis of autologuous antioxidant
ferments.
7.5.5. Vitamine E forms (tocopherols and
tocotrienols). 7.7.5. Comparative research in vivo and
in vitro of antioxidants’ effects on
7.5.6. Carotinoids (β-carotin, lycopene, mitochondrial and nucleus DNA
lutein, astaxanthin, zeaxanthin et al.). damage and certain key genes
of anti-aging, telomeres and cell
7.5.7. Succinic acid derivatives (Mexidol).
membrane structure.
7.5.8. Flavonids, anthocyans and others,
7.7.6. Research antioxidants effect on
polyphenols (Curcumin, Resveratrol,
endocrine control, especially on
and relative compounds (Pterostilben),
epiphysis and hypothalamo-pituitary
Quercetin and Dihydroquercetin,
axis capacity.
catechines and others).
7.7.7. Research antioxidants effect on
age-dependent characteristics of
7.6. RESEARCH the immune system, in particular,
OF GEROPROTECTIVE on immunosenescence, naive
PROPERTIES T-lymphocytes count, self-
OF NEUROTROPIC reactive clones, thin changes in
Drugs subpopulation structure of blood
lymphocytes and immunocompetent
organs.
7.6.1. Finding out the scope of geriatric
diseases and physiologic changes 7.7.8. Research of the antioxidants effects
which are slowed down by deprenyl on models of different geriatric
in order to conduct subsequent diseases – atherosclerosis, diabetes,
clinical research of this drug. retinopathy, osteoporosis and others
and establish the scope of their
7.6.2. Establishing of a specific clinical use (it relates to SkQ in the
mechanism of action of Gerovital first place).
and its role in blocking of Mono-
oxidase in aging deceleration. 7.7.9. Comparative research of
Examination of Gerovital’s effect on antioxidants’ effects on genes
longevity. expression, establishing gene
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patterns which are most important in 7.11.2. Research of the carcinogenic
Medicated Geroprotection
terms of their geroprotective effects properties of the activators of
manifestation. telomerase expression.
7.7.10. Research of the possibility of 7.11.3. Research of a method to elongate
stimulating body's proprietary telomeres with no activation of
antioxidant system. telomerase expression (or with
a subsequent inhibition of its
expression).
7.8. RESEARCH
OF BIGUANIDE 7.11.4. Study of the telomere elongators’
Geroprotective effect on longevity, physiologic
PROPERTIES indicators and pathomorphology of
animals.
7.8.1. Decipher the true mechanism of of
biguanides effect on aging processes 7.12. RESEARCH
and develop ways of approaching GUIDELINES IN
the elaboration of the most effective GEROPROTECTION
ones.
7.8.2. Establish the possibility of clinical 7.12.1. Production of drugs aimed
use of biguanides as anti-aging at lipofuscin accumulation
drugs. slowdown.
7.12.2. Production of drugs aimed at
7.9. RESEARCH lipofuscin degradation.
OF Geroprotective 7.12.3. Research of a possibility to
PROPERTIES OF CALORIC revitalize chromatin with the aid
RESTRICTION MIMETICS of drugs, e.g. histone deacylases.
7.12.4. Development of a fusion therapy of
7.9.1. Explore specific mechanism of damaged spliceosomes.
geroprotective action of caloric
restriction. 7.12.5. Development of drugs and methods
of protein inversion activation.
7.9.2. Verify the role of methionine in caloric
restriction effects. 7.12.6. Drug development in order to
increase chondriokinesis.
7.9.3. Research and study of caloric
restriction mimetics. 7.12.7. Development of a therapy to
reinforce lysosomal enzymes.
7.10. DEVELOPMENT 7.12.8. Formulation of drugs and
OF Drugs TO IMPACT methods to increase expression
P66SHC SIGNALING of useful genes (e.g. Lamp2a,
Lon, proteasome proteins, Klotho
gene).
7.10.1. Synthesize signaling inhibitor р66shc
which reproduces knock-out effects. 7.12.9. Research of specific features of
peptides glycation and glucose
7.10.2. Conduct a research of geroprotective assimilability. Design a drug to
properties and side-effects of such reduce glucose level.
an inhibitor.
7.12.10. Drug development to decelerate
glycation.
7.11. SEARCH OF A SAFE
ACTIVATOR OF TELOMERE 7.12.11. Drug synthesis aimed at prevention
ELONGATION of propagation of mutated
mitochondria DNA clones.
7.11.1. Research of effective activators of 7.12.12. Drug development on the basis
telomere elongation. of metal chelators to prevent
I 49
interaction between beta-amyloid
Medicated Geroprotection
and copper and zinc.
7.12.13. Drug development to destroy cross
linking.
7.12.14. Drug development to stimulate
fibroblast and MSC.
7.12.15. Drug design to selectively remove
T-cells.
7.12.16. Development of methods of
inhibition of immunosenescence
and restoration of neuroendocrinal
and immune systems.
50 I
Section 8
ischemic heart disease. The authors consider
Geroprotectors ischemic heart disease as being a result of
accelerated age-related modifications in the
I 51
8.1. DEVELOPMENT OF GUIDELINES 8.2. DEVELOPMENT OF POTENTIAL
While planning a research the researcher has The listing can include:
to answer three main questions: 1. Peptide epiphysis drugs (Epitalamin and
Epitalon)
1. Is the research cost reasonable in terms
of the amount of animals required to obtain 2. Melatonin
statistically credible results? 3. Metformin
2. Are experimental conditions reproducible, 4. SkQ-1
including animals’ genetics and 5. Deltaran
characteristics? 6. Resveratrol
3. Does the research model meet the 7. Rapamicin
objectives of the research? 8. Succinic acid
9. Glycation inhibiting drugs
8.1.2. Selection of Physiological Age Markers 10. Deprenil
Goals and objectives: determination of 11. Entero sorbents
criterion for physiological age markers and 12. Development of efficient geroprotector
development of a baseline markers list as well combinations
as an extended list thereof.
8.3. DEVELOPMENT OF POTENTIAL
8.1.3. Development of unified test reports GEROPROTECTOR EFFICIENCY
on potential geroprotectors efficiency
in animals (monkeys, rats, mice, fruit ASSESSMENT PROGRAM
flies, hookworms, yeast).
The program is targeted at development
A test report should include the following of a critical review, system and methods
animal data: for geroprotective activity and efficiency
• type, line, sex, assessment of a drug or another preparation.
• housing conditions, Experts could also provide advising on the
• age at the beginning of the test, credibility of additional researches.
• animal randomization principles, Criteria for assessment can be defined
• modes of drug administration, as a proved efficiency degree of certain
recommendations for geroprotectors use.
• dosage and regimen of drug
administration, There are four degrees:
• peculiarities of animals monitoring, 1. There is sufficient proof of the drug
• food and water consumption, geroprotector efficiency confirmed by
• somatic temperature, epidemiological multicenter randomized
researches;
• estrous function (females),
• animals motor performance (tests “open 2. Drug efficiency has been confirmed by
field”, “shuttle maze” and “elevated plus numerous experimental tests on various
maze”), animals, while there is no sufficient efficiency
proof obtained in epidemiological multicenter
• physical strength and fatigability, randomized researches or such proof has
• required biochemical and hormonal tests, been the result of individual monitorings;
including telomere length,
3. There are sporadic reports on drug
• pathomorphological tests, efficiency with high-level reliability;
• life span characteristics,
4. There are sporadic unconfirmed reports on
• statistical methods of data processing. drug efficiency.
52 I
8.4. DEVELOPMENT • Nephrology
3. Scientific-Research Division
Laboratories of:
• molecular biology
• cytogerontology
• pathomorphology
• stem cells
• behavioral and cognitive researches
• physiopathology
• hemadenology
• immunology
• biochemistry
• oncogerontology
• nutrition
• pharmacology and toxicology
• phytogerontology
• physical culture
• ecological gerontology
• mathematical method and statistics
I 53
Section 9
2. The variation of biological parameters
between individuals and the discrepancies
Identification during value- measurement. These
fluctuations can be large enough to blur
of the molecular the distinctions between the measured
parameters.
markers in aging 3. The overlapping of aging events and the
occurrence of illnesses. The risk of the
development of many diseases which, in turn,
can influence the aging process, increases
through the years.
Selected clauses 4. It is not clear yet on how to classify age
changes: it is not known which of them are
significant, and which indicate irreversible
According to common definition – aging age changes and which ones can be ignored. It
biomarkers are the biological parameters is also not known where the threshold borders
of an organism, which independently or in a lie for different age changes at which their
complex combination, define the functionality crossing causes considerable and critical
of an aging organism better than its changes in the organism to occur.
chronological age. 5. Insufficient financial support of the
work connected with the search of aging
Potential biomarkers of aging should meet the biomarkers.
following conditions:
1. To predict the results of the wide range Work on the search for aging biomarkers
of aging tests (biochemical, physiological should include full-scale interdisciplinary
and behavioural) and to do it better than the research with the participation of laboratories
chronological age. in different countries. As an example of the
organization of similar research we can show
2. To predict the remaining life expectancy the European project on the identification of
of the individual, designating the age in longevity genes “GEnetics of Healthy Aging
which about 90% of such a population would (GEHA)”, uniting the effort of scientists in
remain alive. The accuracy of the prediction European countries and in China.
should consider the possibility of the most
widespread illnesses connected with aging A priority research goal is in the identification
occurring. of the set of aging biomarkers for humans and
animals.
3. The procedure for biomarker measurement
should not influence the expected life
expectancy. The primary goals of the research:
1. To verify the already known parameters
Probably, biomarkers with good accuracy changing with the years as possible aging
should not only reflect the changes connected biomarkers for humans and animals.
with the advancement of years, but also
any degenerate processes occurring in an 2. To experimentally find an optimum
organism. The overall target is to learn to combination of aging markers which satisfy
define how the organism's physiological the above-stated definition of an aging
functions will work over the course of aging. biomarker. A priority direction in the given
Finally, the aging biomarkers will be used problem is in the definition of an aging
for developing medicines, or other agents biomarker for humans.
for slowing down the process of aging and 3. To search for new aging biomarkers
increasing general life expectancy.
54 I
9.1. PROCESSING THE 9.1.3.11. Pro-inflammatory cytokines (IL-6,
I 55
twins participating the in research, 9.4.2. Searching for protein aging
56 I
Section 10
processes as it allows one to perform a
I 57
10.1. MATHEMATICAL Modeling development, reproduction and
58 I
10.1.6. Mathematical models of aging of the 10.2.1.1. Elaboration of structural models
I 59
in ecological situations in different 10.3.2.2.5. Mathematical modeling of
60 I
10.3.5. Analysis and development of 10.4.2.2. Development of formal stochastic
I 61
10.5.2. Analysis of population genetics of adaptation, energy redistribution
62 I
Section 11
compounds by microorganisms
I 63
thrombotonin, prostaglandins, 11.4.7. molecular-dynamic process,
64 I
Section 12
12.4. The analysis of the
REPRODUCTION mechanisms of sex
differences in life span:
AND AGING
12.4.1. Social component:
125.4.1.1. Detection of genetics reasons of
behavior risks in males.
I 65
Section 13
13.5. Light regimes and aging:
ENVIRONMENTAL 13.5.1. Intensification of vital activity at light
INFLUENCE as aging-accelerating factor:
13.5.1.1. Reproduction activation;
ON AGING 13.5.1.2. Change of ratio between rest and
activity.
13.5.2. Suppression of neuroendocrinal
regulation in dark regime.
SELECTED RESEARCH DIRECTIONS
13.6. Ionizing radiation and
aging:
13.1. Oxidative stress and aging:
13.6.1. Radiation hormesis;
13.1.1. The rate of living theory verification; 13.6.2. Radiationadaptiveresponse;
13.1.2. The influence of oxygen pressure on 13.6.3. Hyper-radiosensitivityand aging
longevity; acceleration;
13.1.3. The reactive oxygen species 13.6.4. Radiation-induced oncogenesis.
involvement in normal ontogenesis,
hormesis and aging. Hypergravityand life span.
66 I
Once again, we wish to highlight the importance of a complex studying
of the aging processes since aging is the reason and the latent stage
for pathological processes in the majority of tissues and organs
Sarcopeni •
Musculo- adipose infiltration Atrophy of the lacrimal
of the muscles • glands • keratoderma
skeletal system
osteoarthritis • degeneration •
osteoporosis cataractgenesis • Sense organs
age-related macular
Nonmalignant dystrophy • decreased
gypeplasia of the hearing • anosmia
Male genital prostate • cancer of
system the prostate gland •
testicular atrophy
AGING Interstitial fibrosis •
Lungs
emphysema
1. Please, express your opinion on the offered approach to the ordering of materials for the program according to the
structure stated on pages 8-9.
2. Please, answer 12 basic questions on the biology of ageing, formulated on p. 9 (the last column to the offered
structure of the program «Science Against Aging»).
3. Give your opinion on the ordering of inter-related ageing processes and stress resistance, stated in the diagram on
pages 12-13. If possible, make additions, suggestions and updates.
4. Please, inform us if you could take part in the program «Science Against Aging»? If yes, then in what capacity:
as an editor, a developer, or an organizer?
We would be very grateful if you could state the comments, remarks, suggestions and additions to any sections of
the program «Science against ageing» which have been presented in this booklet. Also, we would welcome your
input on those areas which require further development.
longevity.foundation@gmail.com
anti.starenie@gmail.com
Initiator
Mikhail Batin
Chairman of the Board of Trustees of the “Science for Life Extension” foundation (Moscow)
Research Advisor
Vladimir Anisimov
Professor, President of the Russian Gerontological Society of RAS, MD;
N.N. Petrov Scientific Research Institute of Oncology (St.Petersburg)
Developers:
Natalia Anisimova
PhD, Russian N.N. Blokhin Cancer Research Center RAMS (Moscow)
Sergei Anisimov
PhD, Federal D.A. Almazov Heart, Blood and Endocrinology Center (St.Petersburg)
Vladislav Baranov
Professor, Corresponding Member of RAMS, D. O. Ott Research Institute of Obstetrics and Gynecology (St.Petersburg)
Alexey Volchetsky
PhD, “Science for Life Extension” foundation (Moscow)
Roman Zinovkin
PhD, Mitoengineering Center Moscow State University (Moscow)
Sergei Kiselev
Professor, Vavilov Institute of General Genetics RAS (Moscow)
Mikhail Kiselevsky
MD, Professor, Russian N.N. Blokhin Cancer Research Center RAMS (Moscow)
Vasiliy Manskikh
A.N. Belozersky Institute of Physico-Chemical Biology Moscow State University (Moscow)
Danila Medvedev
PhD, “Science for Life Extension” foundation (Moscow)
Anatoli Michalski
PhD, Institute of Control Sciences RAS (Moscow)
Alexey Moskalev
D.Sc(Biol.), Institute of Biology, Komi Science Center, Ural Division of RAS (Syktyvkar)
Vassili Novoseltsev
Professor, Institute of Control Sciences RAS (Moscow)
Evgenia Selkova
MD, Moscow G.N.Gabrichevsky Scientific Research Institute of Epidemiology and Microbiology
Elena Tereshina
D.Sc(Biol.), Russian Research Institute of Gerontology (Moscow)
Coordinators:
Olga Martynyuk
chief editor of the «Science Against Aging» newspaper (Moscow)
Elena Kokurina
executive editor of «In the World of Science» newspaper, supplement to the Russian edition of Scientific American Magazine (Moscow)
Maria Konovalenko
“Science for Life Extension” foundation (Moscow)
SCIENCE AGAINST AGING
www.scienceagainstaging.com