A short presentation regarding translational problems with rejuvenation biotechnologies

1. Translating laboratory anti-ageing
biotechnology into clinical practice
Marios Kyriazis
ELPIs Foundation for Indefinite Lifespans, UK
drmarios@live.it

2. Two Aspects
Pharmaceuticals and
biotechnology can treat
degenerative diseases such as
Alzheimer's, osteoarthritis or
cardiovascular disease
Disruptive biotechnologies may
enable us to repair age-related
damage – but can these eliminate
ageing, with a dramatic extension
of healthy lifespan? No.

3. Important difference!
• Here I discuss the problems of therapeutic interventions directed at
the basic biological process of ageing.
• The discussion is not about individual clinical age-related
degenerative disease.

4. Negligible Senescence = the rate
of human mortality due to age is
negligible
It would be almost impossible
to radically extend lifespan
and achieve a state of
Negligible Senescence, solely
by using these ‘repair-only’
biotechnological
methodologies

5. The Goal of Biotechnology is the End of Death

6. Laboratory research may appear promising, but when it comes to
applying the results of this research on real patients in the
community, then a host of new problems arise
• Kyriazis M, Apostolides A. The Fallacy of the Longevity Elixir: Negligible Senescence May be Achieved, but
Not by Using Something Physical. Curr Aging Sci. 2015;8(3):227-34.
http://www.ncbi.nlm.nih.gov/pubmed/26135528
• Kyriazis M. The impracticality of biomedical rejuvenation therapies: translational and pharmacological
barriers. Rejuvenation Res. 2014 Aug;17(4):390-6. doi: 10.1089/rej.2014.1588.
http://www.ncbi.nlm.nih.gov/pubmed/25072550
• Kyriazis M. Translating laboratory anti-aging biotechnology into applied clinical practice: Problems and
obstacles. World J Transl Med. Aug 12, 2015; 4(2): 51-5. http://www.wjgnet.com/2220-
6132/full/v4/i2/51.htm

7. Bone marrow transplant (stem cells)
Worldwide: 60 thousand BMT performed each year.
If we assume that a minimum 1% of all humans could possibly be
treated with marrow transplant-dependent rejuvenation
biotechnologies each year, then there will be a need to provide 70
million such transplants a year!
Even increasing the current rate, it will take us 10 years to reach 1
million patients
The procedures would need to be repeated, in order to maintain the
status quo.
We would only be able to treat a total maximum of 0.015% of
humans, ever.

8. Another Example
Tissue engineering
• The technology necessary for
developing large amounts of
viable engineered tissue can be
achieved.
• BUT we need to transplant this
engineered tissue in humans.
• Lifelong immunosuppression.
Other tissues??
• The entire procedure would need
to be repeated for other types of
tissue, until all tissues affected by
age-related damage is repaired.
• How many qualified surgeons
needed in order to carry out these
procedures?
• Medical assessments, risk of
infection or thromboembolism,
and other complications of surgery

9. Genetic Therapies
• Pre-existing immunity to the vector,
choice of vector, costs, dose, and
many others need to be addressed.
Non-viral vectors need to be
administered to the patient via the
intravenous route.
• The new gene may not be inserted
correctly on the DNA, or it may be
overexpressed, causing more
problems than it resolves.
• Risk of introducing infection or
inducing cancer.
Potential problems

10. Nanomedicine
Environmental impact remains
unknown. The use of nanomaterials
in bioengineering is being
hampered by a host of unknown
variables: unwanted neutrophil
activation, vascular toxicity,
inflammation, lipid peroxidation.
Nanomedicine in the
present and near-term
future remains
problematic.
There is little information
about these new
materials, and virtually
no useful data on their
bioaccumulation or
toxicity.

11. Lack of time
One cycle of treating one group of sub-clinical damages via disruptive
biotechnologies may take two or three months. The same patient will need to
undergo the procedure again for different organs.
There will not be enough months in the year for each patient in order to have the
full treatment for each and every organ or tissue.

12. Other Issues
Although some therapies could be
developed, these may not by themselves
result in any benefit until other therapies
have also been developed and
deployed…..
For instance, if a therapy is
devised against atherosclerosis
but not against cancer, the patient
will perish from cancer-related
damage, even if their arteries are
healthy
Patients would need to undertake
other rejuvenation procedures
• vaccinations, cytotoxic and other drugs or oral
compounds
• multiple crosslink breakers
• intravenous immunotherapy
• apoptotic-modulators, and other treatment
modalities
• This has to be repeated until all organs or
tissues where there is accumulation of age-
related pathology have been treated.
• All of these procedures will need to be
repeated on the same patient in perpetuity,
to ensure a continual absence of age-related
pathology for an indefinite time

13. The rest of humanity?
The above discussion refers to the
difficulties where we aim to treat just 10%
of humanity spread over a 10 year period.
A fanciful delusion.
What about the difficulties
associated with treating the other
90%?

14. Indefinite Lifespan
This may happen as a result of a
transition from evolution by natural
selection to a state of gene-culture
‘co-evolution’ (or intentional
evolution)
Our continuous integration within a
techno-cultural environment may
cause a shift in the allocation of
repair resources from the germ-line
to the soma, and thus promote a
more effective somatic repair leading
to a reduction of age-related
degeneration.
Humans who are well-integrated
within a wider global ecosystem may
be able to survive longer because
their usefulness to the network is
more important than their demise.

15. ‘Small-world’,
scale-free cellular
networks
Connections between cells.
Most cells in this network
weakly-connected cells
whereas two (black) are
strongly-connected cells.
Damage to strongly-
connected cells is going to
affect huge parts of the
network.

16. Man-computer ecosystem
Comparison with hyperconnected
human
When the human dies, the network is
disrupted

17. Summary
Elimination of age-related
degeneration may happen - but
not through using a physical
therapy.
Don’t wait for others to devise
treatment. All of us need to take
part.

18. Marios Kyriazis
Ageing Summit 2016
drmarios@live.it