A presentation about the need to consider the subject of ageing in a wider and more complex manner, rather than rely too much on reductionism

1. Systems Thinking in Ageing
Research
Marios Kyriazis

2. Definitions of ‘ageing’
•In biology, ageing is
‘the imperfect repair
of time-related
damage’.
•In a medical sense,
ageing is ‘time-related
dysfunction’.

3. Reductionist and mechanistic model of research
=dead end
• no opportunities for
breakthroughs or practical
advancements, which may lead
to a dramatic reduction of age-
related degeneration.

4. ‘systems thinking’
the understanding of the relationships between the parts of
the system in relation to the whole, and the interdependency
of such structures of dynamic systems

5. Elixir of youth
* ‘rejuvenation biotechnologies’
* ‘stem cell interventions’
* ‘anti-senescence drugs’
* ‘parabiosis’
other related interventions

6. Two elements in
ageing
1. Τhe process of ageing itself
(time-related damage and the
inability to repair this
damage). This leads to clinical
dysfunction.
2. Diseases that are
manifestations of this time-
related dysfunction.

7. Ageing
process
Age-
related
diseases
Complex
approach
Physical
Biomedical
Therapies
Results in

8. Drugs or remedies that can be used in ageing
* Senolytics, such as Quercetin, Dasatinib, Navitoclax, or combinations
* Rapamycin
* Lifespan-extending herbs
* Metformin
* Telomere and telomerase modulators
* Sirtuins

9. A ‘systems thinking’ perspective
We need to study the complex, dynamic and
continual adaptation to our environment, in order
to explore effective, non-biomedical, age-
decreasing strategies.

10. The complexity of the treatment must match the
complexity of the process we want to treat
•End our current
thinking based on
magnification (i.e. the
study of magnified
cells, tissues, enzymes,
DNA), which is
reductionist
•Consider how
matters look in
miniaturisation
('zoom-out’)

11. Technology
• The pace of technological
developments is changing
society
• Implications on our biology

12. First Phase Science: a clear separation between
the observer and the object of the observation

13. Second Phase Science: The observer and
the observed are intermingled

14. Third Phase science: Different
interacting viewpoints

15. Molecular Pathological Epidemiology
Combines epidemiology and pathology
• Focuses at a microscopic AND a
macroscopic level
A link between reductionism and
systems thinking
• Social Genomics

16. Hormesis
Homeodynamic space

17. Hormesis
An adaptive response of cells and
organisms to a moderate,
intermittent, challenge.
Hormesis describes phenomena
where there is low dose
stimulation, high dose inhibition.
Nutritional, physical, mental and
chemical challenges may result in
mild damage which upregulates
repair mechanisms. In an attempt
to repair this damage, age-related
damage is also repaired.

18. Examples of hormesis
Nutritional
Physical
Sexual
Social

19. Environmental Enrichment
Experimental animals are
exposed to an enriched
environment- a habitat
augmentation. This has
several positive effects on
health, specifically on
brain and immune
function.

20. Challenge
Here, a challenge is defined as a situation that potentially carries
biological value for an organism, so that the organism is inclined to act.
A challenge provokes action because it represents a situation in which
not acting will lead to an overall lower fitness than acting.

21. A hormetic-cybernetic
approach to ageing
research
The inter-
relationship
between the
different concepts
mentioned
Reductionism HORMESIS Systems Thinking
CYBERNETICS
MolecularPathologicalEpidemiology
FIRST PHASE SCIENCE
SECOND PHASE SCIENCE
THIRD PHASE SCIENCE

22. Systems Thinking
• Non-additive determinism:
A system is not defined by the
sum of all of its individual
components, but there are
emergent properties that add
another layer of complexity in the
system’s behaviour
• Reciprocal Determinism:
Distinct biological and distinct
social factors influence each other
in a complex manner, leading to
results which may be
unnoticeable when only the
biological or only the social
aspects are considered in
isolation.

23. The Indispensable Soma Hypothesis
• We live in an information-rich
technological ecosystem
• Hormetic-style activation of
neuronal stress response
• Enhancement of the function of
the neuron AND downregulate
the function of the germline.
• In the final analysis, we may
encounter a situation whereby a
human-computer hybrid entity is
both biologically and
technologically robust, and able
to survive without any age-
related degeneration, due to a
shifts of repair resources from
the germline to the soma.

24. I quote from my paper
…..within a high-level cognitive
ecosystem, we initiate a series of
upregulation sequences and
involvement of certain evolutionary
functions such as degeneracy,
exaptation, adaptive response (an
appropriate reaction to an
environmental demand) etc., which
cause our body to repair damage
and thus avoid chronic degenerative
diseases such as arthritis, heart
disease, senile dementia, Alzheimer
Parkinson etc. In this way, life span
will increase dramatically.

25. a. Biological amplification: activation of one process locally,
can have beneficial repercussions elsewhere in the body.
b. Challenge propagation: A challenge (for instance a cognitive
encounter with digital technology) will lead to a change in the
environment of the neuron and this change will then act as a
new challenge for other neurons to respond. Therefore, the
adaptation diffuses through the network and results into an
improved performance of the entire network.
c. Selective reinforcement: behaviour modification which
seeks to increase the occurrence of certain desired events, and
decrease the occurrence of certain undesirable events, with
the result that only positive events are retained
d. Exaptation: A character or property that was evolved for one
purpose, facilitating a new function in adaptation of an
organism or a system.

26. CONCLUSIONS
• I tried to highlight the importance of shifting our attention from a
well-defined reductionist thinking to a wider, apparently vague
‘systems thinking’ model with regards to ageing.
• We cannot just rely on simplistic concepts originating from outdated
models of reductionist research.
• We need to move away from intellectually and clinically naïve
concepts involving physical, item-based interventions, and instead
consider a much more complex worldview.

27. Thank you
Marios Kyriazis, drmarios@live.it