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Kyriazis. J Transl Genet Genom 2018;2:7. I https://doi.org/10.20517/jtgg.2018.04 Page 3 of 8

profile. This may render more effective therapies with fewer side effects. PM may also include the creation
of unique combinations of treatments that may benefit specific patients. Based on this model of medicine,
we immediately encounter a problematic contrast with current rejuvenation research. Such research aims
to discover therapies that may be effective in anti-aging, as well as therapies that will be common to all,
ignoring the fact that the aging patient is a unique individual with unique genetic profile and environment.
Instead, a PM-centered approach is needed here [22,25] . This approach must be based on concepts developed
in systems biology (the computational and mathematical modeling of complex biological systems and
interactions) which sees the human body in a more holistic manner, in contrast to the current reductionist
model. In addition, it is possible to gain insights from social genomics, i.e., how our genome is affected by
[26]
external social factors . The influence of these external factors on our biology are paramount. For instance,
the combined effects of lifestyle elements, living environment, and personal habits are magnified when we
also consider the additional influence of the genome, biological processes, clinical condition, medical history,
existing diseases and medication of the target patient. The ideal goal of precision medicine is to find effective
ways to prevent the development of an illness, and also provide solutions that can be helpful in the treatment
of existing conditions.

It is necessary to clarify here that this paper refers to discrete physical therapies or interventions which may,
perhaps, originate from genomic research, and follow a basic principle: the therapy is given by a “therapist”
(such as a physician) to a “patient”, in order to effect a cure of aging. Examples include not only rejuvenation
biotechnologies in general, but also anti-senescence drugs (senolytics) [27,28] such as quercetin, dasatinib,
[32]
[29]
[30]
[31]
navitoclax , drugs or compounds such as sirtuin modulators , rapamycin , lifespan-extending herbs ,
[33]
[34]
metformin , telomere and telomerase modulators . A common characteristic of these is that there is a
clear separation between an outside agent (a physician, surgeon, healer, nutritionist) and the patient (healthy
or unhealthy young or older people).
[35]
Some translational problems associated with such biomedical technologies include practical issues
with harvesting autologous stem cells or genetic material, transplantation surgery (of such material),
immunosuppression, infrastructure of delivery, unknown and unpredictable side effects, reluctance to accept
these technologies as a treatment, inadequate integration and assimilation of genes, unknown variables
relating to genetic cross-talk and over-expression, clinical polypharmacy, drug interactions and non-
[36]
compliance .

The consideration of each of these issues separately, leads to significant translational problems. However, if
we also consider that these therapies must be deployed in combination in order to effect a lasting clinical
benefit, it may be concluded that additional emergent problems will be manifest, and these may negate any
[37]
practical clinical applications . This kind of approach involving a physical therapy, an item, an intervention
that exists materially and can be given physically by a separate observer (physician, healer) to the detached
[38]
patient is inherently reductionist and naïve . This methodology has hitherto been inadequate with regards
to substantially reducing the impact of aging in human subjects [20,21,39] .

ONE EXAMPLE: NON-ADHERENCE
A typical and easy to appreciate example of where genomics fail to be adequately translated into a
[40]
clinical benefit, is the issue of non-adherence to medication . Perhaps, a better term would be “bad-
adherence” meaning that the patient may indeed take the medication, but take it erratically, irregularly
and inappropriately, something that will be reflected in the increased likelihood of side-effects. In this
respect, there are several reasons why an effective laboratory genomic discovery may not be translated as an
[41]
[42]
effective clinical therapy. Reasons include cognitive impairment and depression , asymptomatic disease ,
side effects of the medication, which in the case of aging are likely to be several because a wide range of
[43]
therapeutic interventions will have to be deployed , complexity of the therapeutic approach [44,45] and even