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Mitochondrial ROS and mtDNA fragments inside nuclear DNA as a main effector of ageing: the “cell aging regulation system”
and increase longevity. Clarifying if over-expression of
autophagy genes increases o not mean and maximum
longevity over that of normal controls in mice, and if long-
lived animals have higher autophagy activity than short-
lived ones is urgently needed. The rate of mitROSp at
complex I and the DBI are low in long-lived animals, thus
correlating with longevity in the right sense. In addition,
mtROSp at complex I and autophagy respond to the
environmental pro-longevity signals of the different kinds
of DRs or rapamycin: mitROSp at complex I is decreased
and, autophagy is increased, both collaborating in a
integrated manner to increase longevity.
8. With so few aging effectors reasonably well known
up to now (only three) it seems strongly inappropriate the
pretension of some authors that "MFRTA is dead". Such
conclusion, heavily repeated by some authors through
titles of recent articles is largely based either on: a) low
quality measurements like the use in of unspecific kits to
estimate oxidative stress in naked mole rats (177,178), and
lack of stating if the naked mole rats used for the
measurements were queens (30 years of longevity) or
soldiers (few years of longevity) (177,178); in the second
case a high oxidative stress in naked mole rats would
confirm MFRTA instead of being contradictory with it; or
b) technically well done experiments but based on
hypothesis impossible to be correct, especially those
testing whether over expression of antioxidant enzymes
could increase longevity (for a, and b see more detailed
comments on ref. 29). It was well know from the decade of
1990 on that antioxidants, for various different reasons
described in sections 2 and 3.4, do not control longevity
(2,7,10-12,14,17,23,24,29,32,55). The wrong hypothesis
that "antioxidant enzyme overexpression could increase
longevity" was necessarily destined to falsification,
because it was wrongly formulated from the beginning,
ignoring dozens of previous investigations on the subject.
Avoiding such overexpression experiments would have
saved a lot of time and resources as well as reaching
wrong conclusions highly damaging for gerontology like
erroneously considering the mitochondrial free radical
theory "dead". Such mistake would "eliminate" from
current models one of the two aging effectors changing
longevity in the DRs or rapamycin treatment, mitROSp,
leaving autophagy alone to respond to DRs or rapamycin.
It would "eliminate" precisely the aging effector about
which more positive evidences are available, including the
differences in longevity between mammalian and bird
species. Such pernicious situation for biogerontology
should be avoided.
11. CONFLICT OF INTEREST
None declared.
12. ACKNOWLEDGEMENTS
Results obtained at the author laboratory described in
this review have been supported by 21 grants from the EU,
NIA/NIH (USA), Complutense University of Madrid
(UCM), the Madrid Community, Health Research
Foundation (FISss), and the Ministries of Education and
@Real Academia Nacional de Farmacia. Spain
Technology, of Education and Science, and of Science and
Innovation, to the author received between 1988 and 2014.
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