X-Message-Number: 7776
Date: Fri, 28 Feb 1997 09:11:00 -0800 (PST)
From: Doug Skrecky <>
Subject: Canadian Cryonics News exerpts
The following articles appeared in the Volume 33 November 1996 issue
of Canadian Cryonics News. Apologies is any of you that have seen these
articles before. Does anyone know the answer to the [question] imbedded
in the text?
A THOUGHT EXPERIMENT
By Doug Skrecky
For some time now I have been writing short articles about life
extension and cryonics. I am middle aged and not getting any younger, yet
these efforts seem to have had only a limited practical value. I had not
added any new information to the database about either of these topics.
What I have done is regurgitate what I have read in obscure medical
journals and popularized them in various media. I have a little spare
time currently to do more than this and have been thinking about what to
do.
Of these two topics the field of life extension is obviously much
more important, since the primary determinant for whether either cryonics
or any other post mortum preservation technique actually yields an
"afterlife" will be how much time has elapsed for them to be improved.
One is also reminded of the saying "One bird in hand is worth two in the
bush". I will talk therefore mostly about life extension, but these
comments apply in general to cryonics as well.
The key test for whether a given intervention can slow aging is to
see if it actually increases lifespan. Reducing disease incidence can
achieve this independantly of aging, but any attempts to increase
lifespan based on reducing disease incidence alone can add no more than
about 15 years to ones lifespan. Slowing or reversing the aging process
could in principal add centuries so there is a much larger payoff for
focusing on aging itself rather than the diseases which typically attend
it. To restate this in more detail we might be able, by focusing on means
to lower cancer and cardiovascular disease risks increase average
lifespan from 75 to as much as 90 years, but the maximum lifespan will
remain at about 120. By focusing on aging the sky is the limit, with
average lifespans in excess of 120 years being possible for us and even
more for our children.
It is not practical to test agents for anti-aging effects on either
humans or any other long lived species because of the great expense and
length of time required to yield meaningful results. This would be
tantamount to gambling that either of supplements A, B or C will help one
to live longer and then taking them all and hoping for the best. Does
this sound familiar? Unfortunately this is what most of us having been
doing until very recently.
Useful data can be obtained by testing supplements and other
interventions on short lived animal species. We can become increasingly
confident these may work in humans as well, when a variety of such
animals species have been tested with uniformly positive results. This
has been the route taken with caloric restriction with adequate nutrition
(CRAN), which has been proved to slow aging and in some cases
dramatically extend the lives of the animals so treated throughout their
lifespan from infancy. Only a few dedicated life extensionists are
currently on a CRAN program, since this seems to require a considerable
amount of willpower and self-denial. It also needs to be admitted that
the benefits for CRAN initiated in adulthood are typically rather more
modest than those obtained with initiation in infancy.
The particular strain of animal species that is tested should not be
an abnormally disease prone one since then a large increase in both
average and even maximum lifespan could be obtained by merely reducing
disease susceptiblity. This would not imply that similar benefits (or any
benefits at all) would accrue to a normal strain of the same species,
much less us. So hypertension prone SHR mice are not an option.
If an aging intervention works to retard aging only to a limited
degree then the experiment will have to last the complete lifespan of the
tested animal. In human terms an increase in average lifespan from 75 to
90 might be seen, but only when a similar increase in maximum lifespan
from 120 to 135 is obtained will we know that we are onto something
interesting. Highly effective anti-aging interventions will not need to
be run till the end of the animal lifespan since their average lifespan
would exceed species maximum lifespan in any case.
In order to generate more data on aging interventions there are two
possibilities. (A) Pay a PhD to test short lived animals with a given
intervention. (B) Do it oneself. Possibility (A) is ruled out for all
except those with exceptionally deep pockets such as the Life Extension
Foundation. Even here the pockets are not limitless and to date only a
handful of lifespan tests have been conducted. This leaves us with (B).
The short lived animals that have been used to date have usually
either been rats or mice with lifespans of about three years. The
rationale for using these is that they are easily available, short lived
and are somewhat similar to humans biochemically, so hopefully the aging
process may be similarly modifiable in both. The main problem with
starting out with rats or mice is that they are still relatively long
lived animals and lifespan experiments with them will be expensive and
time consuming, even if one conducts the experiments oneself as a long
term hobby. However arguments which prefer mice to men for
experimentation apply to mice as well as men. There do exist animal
species with much shorter lifespans than mice. We want results and we
want them fast and with little trouble. If some intervention works very
well in a really short lived animal, an experiment to verify this in mice
can be conducted later on. Which would be the best very short lived
species to deal with?.
No mammals fit the bill. The fruit fly drosophilia melanogaster is a
very short lived animal (70 days average) that has probably seem more
work done on it than all of the other very short lived animals put
together. Some others that have seen some work are nematodes, rotifiers
and various water fleas. In order to be easy to work with I limit species
to only those that are easily visible to the naked eye. This eliminates
nematodes and rotifiers. Water fleas have the advantage of not flying
away, but the massive research (and availability of instant fly food from
Carolina Biologicals) argued rather convincingly for fruit flies. I am
accumulating the apparatus needed to commence experimentation with fruit
flies now and will regularly issue updates on my progress and results.
Some dramatic increases in lifespan have been obtained recently for
nematodes (fivefold increase) and for mice (doubled lifespan) using
genetic techniques. However I will be restricting my investigating to
nontoxic supplements that are available for human consumption initially.
In order to make maximum use of my time I plan on using only small
numbers of flies to test each supplement so that many of these can be
tested as quickly as possible. First consideration will be supplements
that have never been tested on any animal species for lifespan prolonging
effects. Various theories of aging will also be used to help select
supplements so that these theories can be tested as well. One example is
biotin. The insulin sensitizing drug chromium picolinate has greatly
extended lifespan of a single species of rodent. Biotin is also an
insulin sensitizer, so it will be tested to yield data on whether insulin
secretion is a reliable aging accelerating factor.
I have talked mostly about life extension here, but would like to
end with a short monologue on cryonics. As with life extension it would
be far more cost effective to do the experiments oneself rather than pay
a PhD to do them. Highly involved experiments using complex equipment are
not an option for cryonics experimentation for the same reasons only very
short lived animal species can be considered for life extension
experiments: time and money. With no perfusion equipment only very small
animal species can be considered for possible revival after freezing and
thawing, since only these could absorb enough cryoprotectant through the
skin to make a difference. Small aquatic animals should get first
preference since they will not drown in water/cryoprotectant mixtures.
Water fleas might be a appropriate species to test. The cryoprotectant
used would have to be highly permeable since only the skin is being used
for uptake. This rules out sugars for example. The cryoprotectants used
or at least their mixtures should not have been tested before to avoid
duplication of effort. Glycerol and DMSO can be omitted for this reason.
An example of a highly permeable cryoprotectant that has not been tested
before (to my knowledge) is triethylene glycol diacetate. This has a
membrane permeability rate that is 44 times as fast as glycerol. If
anyone is interested in conducting cryonics research please let me know.
I can be reached at
BETTER LATE THAN NEVER
By Doug Skrecky
Some attempts to preserve the body of the deceased are somewhat
tardy. However there is at least some hope that even delayed action in
this regard may be able to save some memories. Cultures derived from glia
and astrocyte cells removed from the brains of human corpses have
demonstrated only a slight decrease in the rate of successful culturing
when the postmortum interval was greater than 20 hours.
"Cell Proliferation and the Aging Brain" Age 3: 43-47 1980
IS ADONITOL A SUPERIOR ALTERNATIVE TO GLYCEROL?
By Doug Skrecky
Adonitol (also called ribitol) is a sugar alcohol with a molecular
weight of 152 and a melting point of 102 C. Glycerol by comparison has a
molecular weight of 92 and a melting point of 17.8 C. Although glycerol
has been much used (and perhaps abused) in cryobiology adonitol has been
largely ignored. This may have been a mistake.
Rat embryos cryopreserved in 0.3 M glycerol or 0.3 M adonitol have
survival rates of 16% and 67% respectively. At 1.0 M glycerol yields a
52% survival, while adonitol yields 88%. *1 However when human sperm is
cryopreserved according to procedures optimized for glycerol, mobility
recovery was higher in glycerol than for adonitol. *2 When polyols are
added to skim milk survival of freeze dried bacteria varied as follows:
*3
0.75 M 1.0 M 10%
Organism Adonitol Glycerol Skim milk only
S. lactis T164 100% 53% 10%
S. lactis T215 81 26 9
S. cremoris T162 86 40 12
S. cremoris T55 96 38 10
S. faecium T175 100 5 13
S. thermophilus 98 43 13
L. cremoris 98.3 12 4.6
L. plantarum 100 35 12
L. casei 98.2 32 9
L. murinus 88 41 8
L. fermentum 56 40 1.5
L. leichmanii 87 90 <1
L. bulgaricus 53 2.5 3.6
L. helveticus 49 20 1.4
average: 85 34 7.7
Functional recovery of tissue either cryopreserved or freeze-dried
may be higher if adonitol is substituted for glycerol. Adonitol would
also be safer than glycerol for long-term storage due to its higher glass
transition temperature.
*1 "Cryoprotective Effect of Polyols on Rat Embryos During Two-Step
Freezing" Cryobiology Vol.29 332-341 1992
*2 "Evidence that Membrane Stress Contributes More Than Lipid
Peroxidation to Sublethal Cryodamage in Cryopreserved Human Sperm:
Glycerol and Other Polyols as Sole Cryoprotectant" Journal of Andrology
Vol.14 No.3 199-209 1993
*3 "Protective Effect of Adonitol on Lactic Acid Bacteria Subjected to
Freeze-Drying" Applied and Environmental Microbiology Vol.45 No.1 302-304
1983
INHIBITING GLYCEROL TOXICITY
By Doug Skrecky
Glycerol is metabolized to formaldehyde by living tissue. In isolated
rat liver microsomes BHT, DMSO, mannitol, SOD ,trolox and vitamin E had
no effect on glycerol catalyzed formaldehyde production. However at a
dosage of 0.01 mM the iron chelators desferrioxamine, DTPA and EDTA as
well as the antioxident propyl gallate inhibited formaldehyde production
by 95%, 88% 86% and 91% respectively. Since the lipid soluable propyl
gallate alone has the ability to readily penetrate cell membranes it is
the clear first choice to protect against glycerol toxicity. It appears
that the addition of propyl gallate to all glycerol soltuions currently
used by cryobiologists and cryonics companies is mandates.
Reference: "Role of Iron, Hydrogen Peroxide and Reactive Oxygen Species
in Microsomal Oxidation of Glycerol to Formaldehyde" Archives of
Biochemistry and Biophysics Vol.285 No.1 83-89 February 15,1991
[Question: Has any cryonics company started adding 0.01 mM propyl gallate
to their cryopreservation mix?]
XEROGEL VACCUUM INSULATION
By Doug Skrecky
A new solid xerogel vaccuum insulation is in development at Dow
Chemical Company. Xerogels are microcellular solids prepared by
evaporation of solvents from a solvent/polymer gel. They resemble
styrofoam, but have a much finer cell structure, which is interconnected
or "open" to the external environment. They are potentially less
expensive than similar so-called aerogels since the later requires more
expensive supercritical evaporation at carefully controlled temperatures
and pressures. Xerogels are somewhat denser than aerogels since increased
surface tension causes some shrinkage during drying. Under a soft vaccuum
xerogels have a higher conductivity than silica vaccuum powder
insulation, but below 1.5 torr have a slightly lower conductivity.
Unlike aerogels, xerogels are a potential replacement for vaccuum
powders in high performance insulation systems since the construction
advantages of their monolithic form are not offset by a higher price.
This might make storage containers for cryonics patients (or cryostats)
less expensive to build.
Reference: "Microcellular Polyurea Xerogels for Use in Vacuum Panels"
Journal of Cellular Plastics Vol.32 172-190 March 1996
For more information contact:
Rick L. Tabor
The Dow Chemical Company
Polyurethanes Products Research Laboratory
Building B-1608
Freeport, TX 77541
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