The following is being posted to:
CR Society
Cryonet
Extropians
Sci.cryonics
Sci.life-extension
Transhuman
(A copy of this is at
http://www.infinitefaculty.org/sci/cr/le_expts.htm.)
(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 appreciated.)
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 implications.]
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.
-- Brian Manning Delaney If you feel you must respond by email, please send the email here: <le_expts@infinitefaculty.org> http://www.infinitefaculty.org/sci/cr.htm ---------------------------------------------------
<> CoQ10.
Mech Ageing Dev 1978 Mar;7(3):189-97 Immunological senescence in mice and its reversal by coenzyme Q10. Bliznakov EG UI: 78090829 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=304510&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=2002700&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=7390164&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8423709&Dopt=r 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=2118586&Dopt=r 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=2505007&Dopt=r Life Sci 1994;54(15):1047-57 Sexually low performing male rats die earlier than their high performing peers and (-)deprenyl treatment eliminates this difference. Knoll J, Yen TT, Miklya I UI: 94202993 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8152326&Dopt=r (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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=3126844&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=3361965&Dopt=r
<> L-Dopa.
Science 1977 Apr 29;196(4289):549-51 Levodopa, fertility, and longevity. Cotzias GC, Miller ST, Tang LC, Papavasiliou PS UI: 77150802 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=850799&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8290600&Dopt=r 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8290600&Dopt=r 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=7825823&Dopt=r [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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8010614&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=9701766&Dopt=r
<> 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=9614711&Dopt=r 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 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8852588&Dopt=r (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 span. Dubey A, Forster MJ, Sohal RS UI: 96132652 http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?/htbin-post/Entrez/query%3fdb=m&form=6&uid=8554316&Dopt=r ---------------------------------------------------