X-Message-Number: 12364
Date: Fri, 03 Sep 1999 16:21:48 -0700
From: Brian Manning Delaney <>

Subject: Complete List of Non-CR Experiments Showing An Increase in Maximum Life

(Was, a LONG time ago: Re: Calorie Restriction.)

The following is being posted to:
 CR Society

(A copy of this is at

I meant to get to this many months ago, but some personal
matters have occupied me for most of the last half-year. If
anyone can provide assistance here, it would be much


A recent comment by Natasha Vita-More, on the Transhuman list,
reminded me of the importance of stepping back from thoughts
about what might or might not be possible in four or five or six
decades, and being certain that we actually are still alive
decades from now. Calorie restriction, I contend, is currently
the only appreciably effective life-extension regimen with good
evidence behind it (others might add cryonics here too, where
"evidence" would mean more than merely empirical evidence).
Personally, I'm willing to put up with the hassles of being on
CR for now; but when a newer, equally effective means of
life-extension is available, I'll happily bag CR. Likewise, when
a _currently_ available, non-CR, putatively effective
life-extension regimen garners sufficient scientific support to
enable us to scratch the "putatively," I'll bag CR. One
question, then, is what to make of the handful of existing
studies that purport to show a slowing of aging -- albeit a
small slowing of aging -- by means of something other than CR.

After raising some of these points on Cryonet many months ago, I
got an interesting, challenging response from Thomas Donaldson.
(A quasi-summary post is here:
http://www.cryonet.org/archive/10663. Follow-ups should be easy
to find.)

The main question that was under discussion is whether, in fact,
there are any well-conducted, repeatable (shown by having been
repeated) studies demonstrating an anti-aging effect of
something other than Calorie restriction. Donaldson suggested
that there were. I disagreed. He encouraged me to take a closer
look at some of the studies I hadn't read in a long time
(including some that actually haven't been repeated, but were
nonetheless intriguing), to verify, among other things, that my
claims that they weren't well-conducted were justifiable. To
give the "CR isn't currently the only way to go" thesis a run
for its money, I thought it would be worthwhile to get together
a list of ALL the non-CR studies claiming to have shown an
increase in maximum life span, then examine all of them (which
is to say: I'm STILL not ready to respond to Donaldson's
request! -- sorry; can't be avoided). Such a list may already
exist somewhere on the Web; I looked but couldn't find it. Thus,
I'm wondering if people could help fill in the blanks in the
list below, including those studies referred to in parentheses,
or point me to a list of such experiments, if it exists. (Some
of the blanks below I could fill in myself, especially the
melatonin studies; I just got burned out while trying to finish
the list, and decided that I should wait until I'm certain such
a list doesn't already exist.)

The criteria for the studies are:
1) The authors claim to have produced an increase in maximum
(not merely average) life span.
2) The studies were published in peer-reviewed publications
(non-published conference talks don't count).

[The second question at issue in the Cryonet discussion --
whether Donaldson's claim that CR studies themselves are not
sufficiently oriented towards discovering the mechanism behind
its mode of action -- I will leave for later (and will likely
never get to, interesting though the question be). In brief: I
disagree. CR studies are mostly moving towards a basic science
orientation, which is the right way to discover CR's mechanism,
however much any one study will generally not have global

Below is what I have so far. Some of these may not meet the
above criteria, but it's been claimed by people who seem to know
what they're talking about that they do. In the case of studies
of a substance/regimen that meets the above criteria, I'd also
like to get studies that are negative on the substnace/regimen.

If anyone has additions, please add them. I'll post the whole
list again after I get some additions. (And then after my next
trip to the medical library, I'll post the list with commentary,
will add any other experiments I find, and will remove those
that don't belong.)

I suggest that people who have additions post them to
Sci.life-extension, so that others will know that the effort of
finding particular studies has been done. It's not necessary to
use the format I've used below, though it would be helpful (the
URLs are to the PubMed entries, citation format, with abstracts,
where available).

And if such a list already exists somewhere on the Web, please
post the URL.

When the list is complete, and the studies are assessed, then
examining these questions will be possible:
1) Of those studies which look good but haven't been repeated,
is it that attempts to repeat the study have been tried, and
weren't successful (and it wasn't published, because negative
findings often aren't published)? Or is it simply that the
funding or motivation hasn't been there (because of "orphan" or
similar status, for example)?
2) If it's reasonable to conclude that there are no
drugs/regimens other than CR that can slow aging appreciably (by
as much as CR, or close), what's a reasonable estimate of the
date at which such regimens will be available? And
3) How does the assessed date of the beginning of the post-CR
era affect one's decision to go on CR now? (The big question,
for me.)

Thanks much!
Brian Manning Delaney
If you feel you must respond by email, please send the email


<> CoQ10.
Mech Ageing Dev 1978 Mar;7(3):189-97
Immunological senescence in mice and its reversal by coenzyme
Bliznakov EG
UI: 78090829


<> HGH.
Mech Ageing Dev 1991 Jan;57(1):87-100
Effects of long-term, low-dose growth hormone therapy on immune
function and life expectancy of mice.
Khansari DN, Gustad T
UI: 91163156


<> Dilantin.
Gerontology 1980;26(5):241-6
Effect of treatment with phenformin, diphenylhydantoin or L-dopa
on life span and tumour incidence in C3H/Sn mice.
Dilman VM, Anisimov VN
UI: 80225773


<> DNA/RNA injections?
Was this published anywhere?

<> Deprenyl
Life Sci 1993;52(3):281-8
Chronic treatment of (-)deprenyl prolongs the life span of male
Fischer 344 rats. Further evidence.
Kitani K, Kanai S, Sato Y, Ohta M, Ivy GO, Carrillo MC
UI: 93140503


Life Sci 1990;47(5):415-20
Maintenance on L-deprenyl prolongs life in aged male rats.
Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO
UI: 90370001


Life Sci 1989;45(6):525-31
Striatal dopamine, sexual activity and lifespan. Longevity of
rats treated with (-)deprenyl.
Knoll J, Dallo J, Yen TT
UI: 89364017


Life Sci 1994;54(15):1047-57
Sexually low performing male rats die earlier than their high
performing peers and (-)deprenyl treatment eliminates this
Knoll J, Yen TT, Miklya I
UI: 94202993


(There are some negative deprenyl studies too.)

<> Centrophenoxine?
Biull Eksp Biol Med 1988 Feb;105(2):206-8
[Indices of sympathetic neurocyte transcription and the survival
indices of fractionally and partially chemically
sympathectomized rats against a background of atsefen use].
[Article in Russian]
Potapov SI, Grigor'eva AV, Iarygin VN
UI: 88163935


<> DMAE. (Negative.)
Mech Ageing Dev 1988 Feb;42(2):129-38
Effect of lifetime administration of dimethylaminoethanol on
longevity, aging changes, and cryptogenic neoplasms in C3H mice.
Stenback F, Weisburger JH, Williams GM
UI: 88201387


<> L-Dopa.
Science 1977 Apr 29;196(4289):549-51
Levodopa, fertility, and longevity.
Cotzias GC, Miller ST, Tang LC, Papavasiliou PS
UI: 77150802


<> Melatonin.
Ann N Y Acad Sci 1991;621:291-313
The pineal control of aging. The effects of melatonin and pineal
grafting on the survival of older mice.
Pierpaoli W, Dall'Ara A, Pedrinis E, Regelson With
UI: 91315052


Proc Natl Acad Sci U S A 1994 Jan 18;91(2):787-91
Pineal control of aging: effect of melatonin and pineal grafting
on aging mice.
Pierpaoli W, Regelson W
UI: 94119971


Ann N Y Acad Sci 1994 Nov 25;741:358-63
Melatonin treatment mimics pineal graft action in regulating
brain cortex adrenoceptors in aging mice.
Viticchi C, Bulian D, Pierpaoli W, Piantanelli L
UI: 95126370


[More by clicking on "related" at first one above.]

<> Pineal modification. (Some of the above belong here too.)
Ann N Y Acad Sci 1994 May 31;719:456-60
Pineal cross-transplantation (old-to-young and vice versa) as
evidence for an endogenous "aging clock".
Lesnikov VA, Pierpaoli W
UI: 94280000


<> Epithalamin.
Mech Ageing Dev 1998 Jun 15;103(2):123-32
Pineal peptide preparation epithalamin increases the lifespan of
fruit flies, mice and rats.
Anisimov VN, Mylnikov SV, Khavinson VK
UI: 98367088


<> SOD transgenic experiment.

<> PBN
Biosci Biotechnol Biochem 1998 Apr;62(4):792-4
A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life
span of mice.
Saito K, Yoshioka H, Cutler RG
UI: 98276895


Neurosci Lett 1996 Mar 1;205(3):181-4
Antioxidant treatment with phenyl-alpha-tert-butyl nitrone (PBN)
improves the cognitive performance and survival of aging rats.
Sack CA, Socci DJ, Crandall BM, Arendash GW
UI: 97005289


(PBN, Negative.)
Arch Biochem Biophys 1995 Dec 20;324(2):249-54
Effect of the spin-trapping compound
N-tert-butyl-alpha-phenylnitrone on protein oxidation and life
Dubey A, Forster MJ, Sohal RS
UI: 96132652



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