X-Message-Number: 29422
Date: Sat, 14 Apr 2007 16:15:18 -0700 (PDT)
From: 
Subject: engineered negligible senescence Part I

  What are the odds of living an open-ended lifespan of over a thousand
years? Imagine in the near future, a wealthy businessman decides to
commission a study to investigate whether there is more than a 1% chance
of achieving a thousand year lifespan. In the event of a positive finding,
this study would further attempt to quantify these odds from the
standpoint of a 20 year old, and also from a 50 year old. The study panel
would include skeptics, to be nominated by the tycoon himself. At stake
is a $100 million grant, which would be withdrawn unless a positive
consensus is arrived at, and a practical plan to achieve this is designed.
This grant would be used to impliment the plan to achieve the goal of an
open-ended lifespan.
  Eventually a preliminary consensus report is produced, from which I've
quoted the (imaginary) abstract below. I have inserted my "own" comments
into this abstract with square brackets []. I've also appended some
relevant medical abstracts to stimulate discussion.

Meta-analysis of Extreme Longevity Strategies: Preliminary Report.
J Gerontol A Biol Sci Med Sci. 2012 Mar;67(3):336-372
  "The consensus of this panel is that Engineered Negligible Senescence
(ENS) is theoretically possible, and techniques to acheive this will
become available in the future. The estimated time frame for the
development of ENS is in the first half of the 22'nd Century. Due to
formidable technical challenges a time frame placed anytime in the 21'st
Century is considered unlikely. Conversely ENS is unlikely to be delayed
much beyond the year 2250, due to the continuing rapid pace of advances
in medical knowledge. [The nature of DNA itself being elucidated only in
March 1953 by Watson & Crick, and the seven kinds of ageing in April 2002
by Aubrey de Grey.]
  From the standpoint of a 50 year old no feasible plan with at least a
1% chance of success passes muster. However the development of Engineered
Reversible Cryostasis (ERC) is considered to be theoretically possible,
and techniques to achieve this will become available in the future. The
estimated time frame for the development of ERC is during the second half
of the 21'st Century. If ERC became available within the lifetime of a 50
year old, then it could be used to bridge the gap in time until ENS
becomes available. However the crude and imperfect techniques likely to
be available within the estimated remaining lifespan of a 50 year old do
not meet the 1% threshold.
  No clear panel consensus could be arrived at for the odds of a 20 year
old surviving until ENS. Even if effective antiaging techniques become
available in the near future, these would be unlikely to effect a
sufficiently robust lifespan extension for a 20 year old to benefit
directly from ENS. For example, if a doubled lifespan became
abruptly available by the year 2200, a 108 year old then would only see
his/her remaining lifespan increase from one to two years. However a 20
year old might still be alive when ERC becomes available, and thereby use
this to bridge the gap until ENS is fully developed, and complete reversal
of all aging associated damage is feasible.
  In preparing this report all published longevity trials were
reviewed. Of these 17,568 trials, most involving insects and lower life
forms were discarded because of a lack of correspondence between aging of
these species and aging of humans. [For example, the B vitamin
nicotinamide shortens yeast lifespan, but lengthens that of human cells.]
Most rodent studies were likewise flagged as suspect, since aging of
long-lived rodent species bears only a modest resemblance to human
aging. [P66Shc exerts opposites effects on longevity in rodents and
humans.] The closest approach to human-like aging was deemed to be that of
short lived amyloid susceptible mouse strains. Amyloid accumulation is
here regarded as a core human aging related process, which does not occur
in most short lived animal species. It is noted that the primary
correspondance between rodent and human longevity appears to lie
in the negative effect of dietary glycotoxins. A number of human
intervention trails testing OTC supplements yielded positive longevity
results. These included for example the AREDS & AREDSII trials of
zinc/copper, and a number of small clinical trials involving vitamins D
and K2. Deficiencies of these nutrients are associated with the
exacerbation of a number human aging related pathologies such as thymic
involution(zinc), atherosclerosis (zinc, vitamin K2), sarcopenia (vitamin
D), osteoporosis (vitamin D, K2), and cancer (vitamin D, K2).
  There are a number of trials with extreme results which merit
replication. These include the injections in rodents of fetal thymic
extracts done by Czaplicki, as well as injections of "generic" DNA & RNA
by Odens. The nature of the DNA & RNA used by Odens was unknown until
recently, when the results of a private investigation revealed that is was
bovine thymus DNA, and yeast RNA that was used. However the intervention
which shows the most promise for retarding aging currently appears to be
body temperature reduction. This has been tagged as the single most
powerful modulator of aging in animals.
  There are four $100 million dollar plans which have been
formulated. Follow-up studies are in progress on all four plans. Plan
A: Invest in ENS research. Funding longevity trials, even in short lived
mammals is here regarded as a poor value approach, and unlikely to achieve
much of consequence. With funds limited, a biomarker approach to aging
suppression is the only viable option. The age related pathology most
likely to offer a significant longevity benefit would be reducing amyloid
accumulation. However the number of years gained would still likely be
small since human aging pathologies are also caused by several other
degenerative processes. Only if all degenerative processes are affected
would a large increase in longevity be deemed likely. $100 million is
insuffient to achieve this. Plan B. Invest in ENS research. Investigate
ways and means to reduce glycotoxin accumulation. Same comments apply
here, as apply to plan A. Plan C. Safely reduce body temperature. This is
feasible, and might add several decades of life to a 20 year old, but is
unlikely to benefit a 50 year old much, because of the development
time. [On the plus side, advances on this could probably be made on a low
budget by asking volunteers to measure their temperature every day to test
the effects of various interventions.] Plan D. Invest in achieving
ERC. Currently the main roadblock to ERC appears to be cryoprotectant
toxicity. [It is curious that] Virtually no work has been published on
pretreatments of cells to help block cryoprotectant toxicity. Consensus
is that investing in ERC development might bring forward the ERC date by
a decade or more. Bringing forward ERC would benefit a 20 year old, and
might just possibly help a 50 year old as well.

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