Anna Giulia Cattaneo.
Department of Biotechnology and Life Sciences, University
of Insubria, via J-H Dunant, 3, Varese, Italy.
The definition of aging in healthy humans is a field of
interest not only for geriatrics studies, but for forensic
medicine, demographic and economic sciences too. In spite
of its speculative importance, we can only roughly approximate
this definition. Difficulties raise from different perspectives.
The aging process behaves like an evolution-driven process,
strictly linked to the reproductive potential of species.
To the evolutionary pressure, several other poorly predictable
factors, like chance, environmental risks and insults, are
to be added in the equation.
In humans this event lacks adequate experimental models. To
define live-long processes, we need models belonging to species
whose natural life span is shorter enough to be studied in
more than one generation during the professional live of one
generation of scientists. Not only, to infer data having statistical
significance in humans, the observation should be carried
out in populations large enough to reach statistical meanings.
Such a model does not seem to exist.
The modern experimental biology recognizes and recommends
many useful models defined as "alternative". This
term is addressed to models not involving mammals, but restricted
to established cell lineages, living tissues or organs maintained
or even grown in vitro, monocellular organisms like yeasts,
the fruitfly and other invertebrate well adapted to laboratory
conditions. Among vertebrates, several alternative models
well characterized for in vivo studies include the Xenopus
sp, and some fish, like D.rerio.
None of these models, however, shows the requisites for an
exhaustive study of human aging. In our species this process
is too complex to be reproduced in vitro, a condition adequate
to study simple aspects of aging, not its main mechanisms,
nor to describe the phenomenon in its complexity. In healthy
humans the aging process is limited to the late live, when
the reproductive process is exhausted. Species whose reproduction
potential is evenly distributed along the period of life,
like yeasts and other monocellular prokaryotes adapted to
laboratory conditions, appear therefore to be poorly adequate.
Further restriction are bound to the absence, in invertebrates,
of complex structures, like lungs or cardio-vascular system.
Finally, the energetic cost for maintaining homeothermy must
be kept in mind. Keeping together all these considerations,
an acceptable model of human aging should be searched between
mammals usually bred in laboratory, mainly rodents. In this
manner, the choice is restricted also to species who age at
the end of their reproductive life. The observations will
necessarily be limited to fewer individuals that expected
in population studies, and this limitation is the price of
a more accurate model. And however, the model still lacks
accuracy, because the aging events differs in humans and in
A second difficulty rises from the absence of sure markers
of senescence, and especially by the complete lack of specific
gene linked to the process of senescence, or "gerontogenes",
a term used by Rattan (FASEB J, 1995, 9:284-286). Processes
determining an irreversible aging are mainly linked to oxidative
damage of cell structures: aging starts when the aggressions
overcomes the maintenance and repair systems of the organism.
While many genes have been identified, whose function is linked
to these aging mechanisms, none of them has evolved to cause
accumulation of molecular damage or to determinate the life
Being the senescence, at least apparently, more linked to
this epigenetic modifications than to the genome itself, a
powerful tool to approaching this question could be the metabonomics.
The term refers to the comprehensive study of set of parameters
representative of entire metabolic pathways depicted simultaneously.
This methods is newly accessible by the development of experimental
procedures linked to the recording of magnetic resonance spectra,
applied to the molecular content of blood, urine and other
biological specimens. Every spectrum can be resolved in relation
to the main peaks, corresponding to different metabolites.
The overall procedure is minimally invasive, rapid, powerful
and highly reproducible. While at the present limited to research,
the method is very promising in many complex field, like the
assessment of life span and aging in humans. Its standardization
is in progress and advancement are rapidly achieved, the cost
is progressively reducing. The major limitation is, at the
present, represented by the low number of technicians trained
for the interpretation of results, requiring basis of advanced
If metabolism is at the basis of the human aging process,
a specific marker should eventually be found with the development
of this powerful descriptive means, and samples of population
large enough to sustain a robust statistical analysis should
be obtained at reasonable time and cost. Finally, a distinctive
profile of healthy aging process should be differentiated
from other correlated causes of illness and death.
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