the ageing summit - london 2016

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Translating laboratory anti-ageing biotechnology into clinical practice

Marios KyriazisELPIs Foundation for Indefinite Lifespans, UK

drmarios@live.it

Two AspectsPharmaceuticals 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.

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.

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

The Goal of Biotechnology is the End of Death

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

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.

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

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

NanomedicineEnvironmental 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.

Lack of timeOne 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.

Other IssuesAlthough 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

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%?

Indefinite LifespanThis 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.

‘Small-world’, scale-free cellular networksConnections 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.

Man-computer ecosystem

Comparison with hyperconnected human

When the human dies, the network is disrupted

SummaryElimination 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.

Marios KyriazisAgeing Summit 2016

drmarios@live.it

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