Transcript poster

Non-programmed versus programmed aging paradigm
Giacinto Libertini (Independent Researcher, [email protected], www.r-site.org/ageing)
IAGG-ER 8th Congress – 23-26 April 2015, Dublin, Ireland
Two opposite paradigms try to explain aging [1], here defined as “age-related progressive fitness decline (i.e. mortality increase) in the wild” :
Non-programmed aging (“Old Paradigm”): Natural selection
Programmed aging (“New Paradigm”): Natural selection favor genes
IS UNABLE to contrast organism age-related decay [2]
that DETERMINES AND REGULATES organism age-related decay [3]
Aging: perhaps the main FAILURE of evolution!
Aging: perhaps the main ACHIEVEMENT of evolution!
There are many data and arguments that are incompatible with the Old Paradigm while are predicted by the New Paradigm or compatible with it [4]
(1) Evidence: Aging is not at all universal as there are many species with "Indeterminate Lifespans
and Negligible Senescence” [5].
Old paradigm: This is not predicted by non-programmed hypotheses and is hardly compatible
with them [3, 6].
See Fig. 1
New paradigm: Predicted by the New Paradigm and necessary for its validity [3].
(3) Evidence: Caloric restriction increases lifespan [4]
Old paradigm: For disposable soma hypothesis caloric restriction
should REDUCE lifespan [8].
New paradigm: The evidence is not in contrast with the New
Paradigm [4].
(2) Evidence: Great inter-specific variation of aging rates [5, 7].
Old paradigm: Some variations of aging rates are not related with the hypothesized
causes [7].
New paradigm: All variations of aging rates are explained by the New Paradigm or
compatible with it [4].
(4) Evidence: The natural observation shows numberless cases where an individual sacrifices itself or a blood relative [5].
Old paradigm: Aging cannot be favoured by natural selection because it is clearly disadvantageous for the individual [2].
New paradigm: The above said cases are now defined as “phenoptosis” [9] and show that, even if a phenomenon - as aging is damaging for the individual, it may be favoured by the evolution in terms of supra-individual selection [10].
See Fig. 2
(5) Evidence: Age-related mortality increases at ages existing in wild conditions [12, 13].
Old paradigm: This is obstinately denied by some supporters of the old paradigm [2, 14]!
New paradigm: This is perfectly compatible with the New Paradigm and indispensable for its validity [15].
The concept of “phenoptosis” [9, 10] includes a large category of
well-known phenomena [5] characterized by the self-sacrifice of an
individual (genetically caused / induced and regulated, & favored by
natural selection, in terms of supra-individual selection).
Aging (“slow
phenoptosis” [11])
Autogeny
Fig. 1 - There are numberless animals with no age-related mortality
increase, defined “animals with negligible senescence” [5] or “ageless
animals” (http://www.agelessanimals.org). Rockfishes are the best
studied among them. Rougheye rockfish (left) lives as old as 205 years
in the wild. For Yelloweye rockfish (right), living as old as 118 years,
commercially caught off Sitka, Alaska, "16% of the fish going to
people's dinner tables were 50 years of age or older, with several over
100 years old!" (from the above-mentioned site).
Aphagy in
adult insects
Death after
spawning
Endotokic matricide
Etc.
Hormonally triggered
senescence in plants
Death of the male associated
with mating / reproduction
Fig. 2 – New Paradigm: aging is a particular type of “phenoptosis”
Fig. 3 - Inverse relation between extrinsic mortality (m0) and the
proportion of deaths due to intrinsic mortality (mi). Figure from
[12] redrawn with modifications and the addition of data from a
human population in wild conditions [16].
(6) Evidence: In a comparison of species, the proportion of deaths due to intrinsic mortality is inversely related to extrinsic mortality [12].
Old paradigm: A direct relation is clearly predicted [2]. This contradiction is well known [12], but no explanation has been proposed.
New paradigm: This inverse relation was explicitly predicted on theoretical grounds well before its precise documentation in the wild [15].
See Fig. 3
(7) Argument: It was mathematically demonstrated that the cumulative effect of many hypothetical genes that are harmful at later ages cannot cause an age-related increasing mortality [15].
Old paradigm: For the Mutation Accumulation hypothesis, aging would be caused by the cumulative effects of many genes harmful at later ages [17].
New paradigm: No supporter of the Old Paradigm has ever tried to invalidate the above-mentioned demonstration, which is essential both to falsify Mutation Accumulation hypothesis and to
allow the tenability of adaptive aging theories.
(8) Evidence: For many species, there is an age-related progressive decline of cell turnover capacities for all cell types with turnover. For some cell types without turnover there is dependence on
other cells with turnover that slows down with age [18, 19]. This phenomenon, which clearly compromises the fitness, is genetically determined and regulated.
Old paradigm: The limits in cell turnover, as they are genetically determined and modulated and determine an age-related fitness decline, cannot be explained as caused by the accumulation of
harmful effects and so must have a different acceptable explanation. The only proposed explanation is that these cell limits defend organism from cancer [20, 21], but, for our species in wild
conditions, mortality increase precedes any significant mortality by cancer and so this explanation is untenable [16].
New paradigm: Genetically determined and modulated phenomena that cause an age-related fitness decline are indispensable for the validity of the New Paradigm [18, 19].
(9) Evidence: Cells pass from a cycling state, in which they can duplicate, to a non-cycling state, where cells cannot duplicate, through the random activation of a mechanism with a probability
inversely proportional to the reduction of telomere length [22] (“on/off cell senescence” [4]).
Old paradigm: Not explained by and incompatible with the Old Paradigm [4].
New paradigm: Compatible with the New Paradigm and necessary for its validity as part of the mechanisms that gradually determine ageing [4].
(10) Evidence: The progressive telomere shortening compromises the functions of subtelomeric region, which has delicate regulatory activities [23] (“Gradual cell senescence” [4])
Old paradigm: Not explained by and incompatible with the Old Paradigm [4].
New paradigm: Compatible with the New Paradigm and necessary for its validity as part of the mechanisms that gradually determine ageing [4].
Empirical data and theoretical arguments show that the Old Paradigm is untenable, cannot be presented as a scientific thesis and has only a historical value.
On the contrary, the New Paradigm is clearly compatible with the empirical data and the theoretical arguments.
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