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Page 2 of 8 Kyriazis. J Transl Genet Genom 2018;2:7. I https://doi.org/10.20517/jtgg.2018.04

a framework explaining certain basic biological mechanisms. In a reductionist model, we consider a
[3]
complex issue such as aging, and then choose to study in detail a central, albeit limited component .
Unfortunately, this has also encouraged others to develop a more widespread reductionist thinking in
terms of therapeutic approaches, and examples abound in the popular literature (see, for example: https://
www.calicolabs.com, and https://en.wikipedia.org/wiki/Strategies_for_Engineered_Negligible_Senescence).
Reductionism works up to a point, but then a more comprehensive “systems thinking” has to be developed
[4,5]
with regards to treating aging . This explores the complex relationships between the parts of a dynamic
[6]
system in relation to the whole, and the interdependency of such structures of dynamic systems . Despite
a large number of reports that a drug, nutrient, procedure, compound or other, prolongs healthy lifespan
in laboratory animals, human beneficial mirroring effects have yet to be realized [7-17] . In part, this is due to
the reductionist method employed by the vast majority of researchers which does not take into account the
unique characteristics of humans. This review paper concentrates on evidences pointing at the difficulties
that may be encountered during such reductionism-based rejuvenation approaches. Here, rejuvenation
essentially means “the reversal of the biological process of aging”. The paper also concentrates on the
specific cases of genetic therapies and presents evidences about the difficulties that may be encountered
in developing effective medical rejuvenation therapies and in translating laboratory genomic research into
everyday clinical practice.

The review is based on systematic literature search of the databases of PubMed, Embase, Google Scholar,
Medline and Cochrane, concentrating mainly on papers published in the last 5 years. Papers presenting a
“systems thinking” approach are considered, and the main concepts are included, strengthening the general
thrust of this review. Papers presenting researches based on reductionism are also included, in order to
highlight the contrast between the current approach and a more complex-oriented thinking. The purpose is
to concentrate on emerging thinking pointing at a more systematic consideration of aging, instead of merely
repeating well-known reductionist and mechanistic themes.

DISCUSSION
In the world of scientific research aiming to provide treatments for age-related disorders, it is becoming
increasingly relevant to think along the mantra of our times: “To provide the right care to the right
[18]
patient at the right time”. Nevertheless, some researchers and academics study the scope of disruptive
biotechnologies and other reductionist models, hoping that this approach may help repair specific age-
related damage, reduce the impact of degeneration and thus increase healthy lifespan. The translational
problems, however, remain formidable [19-22] . The difficulties in translating laboratory anti-aging research into
clinical practice are very easily appreciated by a simple test. A PubMed online search (18 May 2018) of the
term “rejuvenation biotechnologies in aging” shows 99 papers discussing theoretical or laboratory aspects
of rejuvenation biotechnologies. Instead, a search of “clinical applications of rejuvenation biotechnologies
[22]
[23]
in aging”, reveals just one relevant paper . Henney states: “Putting it bluntly, how can such reductionist
approaches possibly help us predict and test, let alone understand how a new medicine will work, when given
to a patient in the target treatment group, which, in the case of the major illnesses that are being targeted
by personalization strategies, is likely to be over 65, with a number of co-morbidities and already taking a
number of other medications? So is it really that surprising to encounter failures in efficacy in the clinic? In
our understandable enthusiasm to follow the path laid by the genome revolution, generating an evermore
intricate map of human disease at the molecular level, we appear to have forgotten, or at least relegated the
importance of an understanding of the physiological context”.

Instead of considering general approaches, it is imperative to focus on concepts derived from an emerging
[24]
branch of medicine, namely precision medicine (PM) . In PM, healthcare in general, and therapies in
particular, are customized to the needs of individual patients and can be based on the patient’s specific genetic