Friday, August 01, 2008

Life-Extension Drugs

Dear All,

I would greatly appreciate your advice, please, on any recent review of life-extension drugs, when applied to animal models (mice, rats, etc.).

Specifically, what are the typical effect sizes for these drugs in terms of percent increase in median lifespan (50% survival time)?

Are there some typical examples of drugs for the following specific life-extension patterns:

1. Improving the early survival only ("rectangularization" of the survival curve).
Also when/if this happens, is there a delay in onset of any other symptoms of aging?

2. Improving survival at all ages (parallel shift of the survival curve to older ages).

3. Improving the old-age survival only ("de-rectangularization" of the survival curve).

Please advise, by posting your comments here.

Thank you!

-- Leonid Gavrilov, Ph.D.
Website: http://longevity-science.org/
Blog: http://longevity-science.blogspot.com/
My books: http://longevity-science.org/Books.html

P.S. Here is what I have found so far:

Life Extending Interventions

Intervention Name (In Alphabetic order), Organism, Aging Phenotype

(R)-N-(2-heptyl)-N-methylpropargylamine, Drosophila melanogaster, No effect on life-span,
2-mercaptoethanol , Mus musculus, Life-span extension
2-mercaptoethylamine hydrochloride, Mus musculus, Life-span extension
60% Oxygen, Rattus norvegicus, Shortened life-span

A
Ablation of dilp2 producing neurosecretory cells, Drosophila melanogaster, Life-span extension Accelerated photoperiodic cycle, Microcebus murinus, Shortened life-span
Acetyl-L-Carnitine, Rattus norvegicus, N/A
alpha-phenyl-N-t-butyl-nitrone, Homo sapiens (cell culture), Life-span extension
alpha-phenyl-N-t-butyl-nitrone, Mus musculus, Life-span extension
alpha-phenyl-N-t-butyl-nitrone, Musca domestica, Shortened life-span
Antimycin A , Caenorhabditis elegans, Life-span extension
Antimycin A, Saccharomyces cerevisiae (chronological), Shortened life-span
antioxidant drug EUK-134, Musca domestica, Shortened life-span
antioxidant drug EUK-134, Caenorhabditis elegans, Life-span extension
antioxidant drug EUK-8, Musca domestica, Shortened life-span
antioxidant drug EUK-8, Caenorhabditis elegans, Shortened life-span
antioxidant drug EUK-8, Caenorhabditis elegans, Life-span extension
Antioxidant treatment, Rattus norvegicus, No effect on life-span
Axenic growth, Caenorhabditis elegans, Life-span extension

B
Butein , Saccharomyces cerevisiae (replicative), Life-span extension
Butylated hydroxy anisole, Zaprionus paravittiger, Life-span extension
Butylated hydroxytoluene, Drosophila bipectinata, Life-span extension

C
Caloric restriction, Macaca mulatta, N/A
Caloric restriction, Rattus norvegicus, Life-span extension
Caloric restriction, Saccharomyces cerevisiae (replicative), Life-span extension
Caloric restriction, Caenorhabditis elegans, Life-span extension
Caloric restriction, Drosophila melanogaster, Life-span extension
Caloric restriction, Frontinella pyramitela, Life-span extension
Caloric restriction, Canis lupus familiaris, Life-span extension
Caloric restriction, Ceratitis capitata, No effect on life-span
Caloric restriction, Asplanchna brightwelli, Life-span extension
Caloric restriction, Lebistes reticulatus, Life-span extension
Caloric restriction , Daphnia pulex, Life-span extension
Caloric restriction Brachionus calyciflorus Life-span extension
Caloric restriction Asplanchna girodi Life-span extension
Caloric restriction Brachionus patulus Life-span extension
Caloric restriction Brachionus plicatilis Shortened life-span
Caloric restriction Euclanis dilatata Life-span extension
Caloric restriction Encentrum linnhei Life-span extension
Caloric restriction Keratella testudo Shortened life-span
Caloric restriction Philodina acuticornis Life-span extension
Caloric restriction Synchaeta pectinata Shortened life-span
Caloric restriction Tokophrya infusionum Life-span extension
Caloric restriction Homo sapiens N/A
Caloric restriction Mus musculus Life-span extension
CDTA Drosophila melanogaster Life-span extension
Cold stress Haematobia irritans Life-span extension
Continuous dark Asplanchna brightwelli Life-span extension
Copper gluconate Mus musculus Shortened life-span
Cortisone Asplanchna brightwelli Life-span extension
Curare Asplanchna brightwelli Life-span extension

D
D-glucosamine Saccharomyces cerevisiae (replicative) No effect on life-span
D-Glucose Saccharomyces cerevisiae (replicative) Life-span extension
D-Glycerol Saccharomyces cerevisiae (replicative) Life-span extension
D-sorbitol Saccharomyces cerevisiae (replicative) Life-span extension
D-Xylitol Saccharomyces cerevisiae (replicative) Life-span extension
Decreased oxygen concentration Homo sapiens (cell culture) Life-span extension
Decreased temperature Asplanchna brightwelli Life-span extension
deprenyl Rattus norvegicus Life-span extension
deprenyl Mesocricetus auratus Life-span extension
deprenyl Canis lupus familiaris Life-span extension
deprenyl Mus musculus Life-span extension
deprenyl Drosophila melanogaster No effect on life-span
deprenyl Rattus norvegicus Shortened life-span
Dietary cadmium Drosophila melanogaster Shortened life-span
Dietary iron Drosophila melanogaster Correlation
Dietary restriction of coenzyme Q Caenorhabditis elegans Life-span extension
Dietary restriction of coenzyme Q Drosophila melanogaster Shortened life-span
Diiodomethane Drosophila melanogaster Life-span extension
Diphenylhydantoin Mus musculus Life-span extension
DNA and RNA Injection Rattus norvegicus Life-span extension

E
Ectopic extrachromosomal rDNA circle (ERC) induction. Saccharomyces cerevisiae (replicative) Shortened life-span
EDTA Mytilina brevispina var redunca Life-span extension
EGb 761 Caenorhabditis elegans Life-span extension
EGTA Mytilina brevispina var redunca Life-span extension
Epithalamin Drosophila melanogaster Life-span extension
Ethoxyquin Mus musculus Life-span extension
Exercise Mus musculus No effect on life-span
Exercise Rattus norvegicus Life-span extension

F
FCCP Saccharomyces cerevisiae (chronological) Life-span extension
Fisetin Saccharomyces cerevisiae (replicative) Life-span extension
Fish oil Mus musculus Life-span extension

G
Galactose feeding Drosophila melanogaster Shortened life-span
germ line ablation Caenorhabditis elegans Life-span extension
germ line ablation Pristionchus pacificus Life-span extension
Growth on carbenicillin treated bacteria Caenorhabditis elegans Life-span extension
Growth on kanamycin treated bacteria Caenorhabditis elegans Life-span extension
Growth on UV-killed bacteria Caenorhabditis elegans Life-span extension

H
Heat Shock Saccharomyces cerevisiae (replicative) Life-span extension
Heat Shock Caenorhabditis elegans Life-span extension
Heat Shock Drosophila melanogaster Life-span extension
Hibernation Mesocricetus brandti Life-span extension
High Osmolarity Saccharomyces cerevisiae (replicative) Life-span extension
Human Growth Hormone Therapy Rattus norvegicus No effect on life-span
Human Growth Hormone Therapy Homo sapiens N/A
Human Growth Hormone Therapy Mus musculus No effect on life-span
Hypergravity Drosophila melanogaster Life-span extension

K
Kinetin dietary supplementation Zaprionus paravittiger Life-span extension

L
L- carnosine Homo sapiens (cell culture) Life-span extension

M
Magnesium thiazolidine-4-carboxylic acid Aedes aegypti Life-span extension
Melatonin Mus musculus Life-span extension
Melatonin Drosophila melanogaster No effect on life-span
Melatonin Drosophila melanogaster Life-span extension
Methionine Mus musculus Shortened life-span
Methionine Zaprionus paravittiger Life-span extension
Methionine restriction Rattus norvegicus Life-span extension
Methionine restriction Mus musculus Life-span extension
Modified Mediterranean diet Homo sapiens Correlation

N
N,N'-diphenyl-1,4-diphenylenediamine Caenorhabditis elegans No effect on life-span
N-acetylcysteine Drosophila melanogaster Life-span extension
N-benzyl hydroxylamine Homo sapiens (cell culture) Life-span extension
N-methyl hydroxylamine Homo sapiens (cell culture) Life-span extension
N-t-butyl hydroxylamine Homo sapiens (cell culture) Life-span extension
Nicotinamide Homo sapiens (cell culture) No effect on life-span
Nicotinamide Saccharomyces cerevisiae (replicative) Shortened life-span
Nicotinic Acid Saccharomyces cerevisiae (replicative) No effect on life-span Nordihydroguaiaretic acid Aedes aegypti Life-span extension

O
Ovary transplantation Mus musculus Life-span extension
Oxygen pretreatment Caenorhabditis elegans Life-span extension

P
Paraquat Saccharomyces cerevisiae (chronological) Shortened life-span
PBA Drosophila melanogaster Life-span extension
Phenformin Mus musculus Life-span extension
Prevention of flight Musca domestica Life-span extension
Prevention of mating (by removal of females) Drosophila melanogaster Life-span extension Propyl gallate Zaprionus paravittiger Life-span extension

R
R-Alpha-Lipoic Acid Rattus norvegicus N/A
Repeated Mild Heat Shock Homo sapiens (cell culture) No effect on life-span
Resveratrol Saccharomyces cerevisiae (replicative) Life-span extension
Resveratrol Saccharomyces cerevisiae (chronological) No effect on life-span
Resveratrol Caenorhabditis elegans Life-span extension
Resveratrol Drosophila melanogaster Life-span extension
Resveratrol Saccharomyces cerevisiae (replicative) No effect on life-span
Retinoic acid Homo sapiens (cell culture) Life-span extension
Royal Jelly Mus musculus Life-span extension

S
Sodium borate Drosophila melanogaster Life-span extension
Sodium citrate Mytilina brevispina var redunca Life-span extension
Sodium cyanide Saccharomyces cerevisiae (chronological) Life-span extension
Sodium hypophosphite Zaprionus paravittiger Life-span extension
Sodium selenite Zaprionus paravittiger Life-span extension
sodium tartrate Mytilina brevispina var redunca Life-span extension

T
Tamarixetin Caenorhabditis elegans Life-span extension
Tea extract Drosophila melanogaster Life-span extension
Telomere length Saccharomyces cerevisiae (replicative) N/A
Thyroxine Rattus norvegicus Life-span extension
Tryptophan Restriction Mus musculus Life-span extension
Tryptophan Restriction Rattus norvegicus Life-span extension

U
UV radiation Asplanchna brightwelli Shortened life-span

V
Vitamin C Caenorhabditis elegans No effect on life-span
Vitamin C Homo sapiens (cell culture) Life-span extension
Vitamin E Asplanchna brightwelli Life-span extension
Vitamin E Zaprionus paravittiger Life-span extension
Vitamin E Philodina acuticornis Life-span extension
Vitamin E Mus musculus No effect on life-span
Vitamin E Caenorhabditis elegans No effect on life-span
Vitamin E Caenorhabditis elegans Life-span extension

Home:
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and
Longevity Science: Life-Extension Drugs
Shorter weblink:
http://tinyurl.com/62b78o


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Wednesday, April 11, 2007

Edmonton Aging Symposium

Greetings,

Take a look at interesting presentations given at the recent Edmonton Aging Symposium in Canada, which are now publicly available online here:

The following talk has caught my particular attention:

The Damage of Aging: Present Possibilities and Future Therapies
Huber Warner

This talk argues that the role of damage accumulation in the aging process is probably exaggerated -- particularly for oxidative damage to both nuclear and mitochondrial DNA. This counterintuitive conclusion is based on recent findings that mice defective in superoxide dismutase defence against oxidative damage do NOT live shorter lives, despite observed extensive damage to both nuclear and mitochondrial DNA. Something to think about.

This presentation goes much further, claiming at slide # 9:


Vitamins A, E may be unhealthy
(JAMA 2/28/07 and reported in National Post; March 1, 2007)


This slide also says that Vitamin A increases the risk of death by 16%, and ß-carotene increases the risk of death by 7%.

This is where you have to listen the recorded presentation itself (available at the weblink listed above), to find out that the author himself does not agree with these claims.

So, for each presentation it is better first to download the Power-Point Presentation, then to start the audio of the presentation, and to follow the voice of the speaker clicking the next slides of his Power-Point Presentation.

Interestingly, a similar idea that damage to mitochondrial DNA has still unclear relation to aging was also discussed in another talk:

Mitochondrial DNA Mutations and Their Possible Role in Brain Aging
Konstantin Khrapko

Why additional damage does not always shorten lifespan?
This is indeed a challenge for the evolutionary theories of aging, assuming that “natural selection will always be in greatest opposition to the decline of the most senescence-prone system” and, therefore “senescence should always be a generalized deterioration,'' with all the destruction pathways being equally important.
However this problem can be easily resolved by the reliability theory of aging that emphasizes the existence and the key role of the "weakest links" in system's reliability. If these "weakest links" are not affected, then the damage in other places may have no apparent effects on system's failure.

See also the video of this exciting talk with somewhat intriguing title:

The Color Code and a Rainbow of Health
James Joseph PhD. - Tufts University

This is a rare combination of good science, humorous easy-to-understand presentation with important practical implications for your own health through simple nutrition changes. Dr. James Joseph presented the results of his studies on the effects of a diet high in fruits and vegetables in preventing age-related disease and the impact on behavior with a primary focus the improvement in neurological function and reduction in Alzheimer's symptoms. His lab has shown that blueberry supplementation was able to offset the deleterious consequences on behavior associated with amyloid plaques in mice prone to developing these deposits. The mechanisms by which the active molecules within blueberries are able to increase the generation of new neurons in the brain as well as the pathways by which these molecules help to enhance neuronal signaling and ultimately communication is an area of intense study in Dr. Joseph's lab with results which can potentially be applied to immediately decrease the impact of aging on behavior. Just a short word of caution: it was all done on laboratory animals (rats and mice) only; no similar studies on humans were reported in this presentation.

See also the "Head-to-Head" debates on the Ethics and Desirability of Life-Extension, which is now available here:

These debates are between the advocate of life-extension Gregory Stock and his opponent Daniel Callahan, with Aubrey de Grey as a moderator.

What pleasantly strikes me here is that this contentious issue is discussed during the debates in an academic and very respectful way -- see it yourself!

Very optimistic vision on the economic sustainability of a future life-extension was provided by Ronald Bailey in his talk "Estimating Your Future's Options", see video here.

I wish this talk be longer and more detailed in terms of justification of the optimistic vision for economics of life-extension. Also I feel that even if life-extension is not socially profitable, it still deserves to be pursued, because I believe that human life has its own value, beyond the money dimension.

Overall, these are very interesting and useful records to see and listen.

Please feel free to post your comments on these records below!

Key words:
Edmonton Aging Symposium, Huber Warner, Konstantin Khrapko, James Joseph, Gregory Stock, Daniel Callahan, Aubrey de Grey, Ronald Bailey, life-extension, damage, reliability theory, carotene, DNA, longevity, oxidative damage, risk of death, vitamin A, vitamin E, polyphenolics

Home:
http://longevity-science.blogspot.com/2007/04/edmonton-aging-symposium.html

To read comments on this review, and to post your own thoughts, click here.

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