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

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The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans

Discussion of a new book The Biology of Human Longevity by Caleb Finch


Greetings,

Here is a new book for discussion:

The Biology of Human Longevity:
Inflammation, Nutrition, and Aging in the Evolution of Lifespans
by Caleb E. Finch (Hardcover - Jul 17, 2007)


Here are my preliminary comments made after the first reading of this book:

This is a monumental book, which reviews and discusses over 3,000 scientific publications on mechanisms of aging and longevity, with special emphasis on the role of inflammation in senescence and age-related degenerative diseases. The author is an internationally recognized leader in the field of biogerontology, and his volume could serve as a useful reference book for a wide readership including biomedical scientists, biogerontologists and clinicians in areas of vascular disease, diabetes, obesity, Alzheimer disease and other neurodegenerative diseases, genetics of aging and longevity, animal models of aging, anthropology and primatology, evolutionary biology, demography and epidemiology.

This volume is not a particularly easy reading, because of the complexity of the study topic with mixed and sometimes even controversial research findings, making it difficult to reach general conclusions. Fortunately the book is well illustrated with numerous tables and pictures (136 illustrations), which makes it much easier to follow.

The book starts with a discussion of the role of inflammation and oxidation in aging and chronic diseases (chapter 1) including an overview of experimental models for aging studies, description of inflammation process, as well as four types of damage (free radical damage, glyco-oxidation, chronic proliferation, and mechanical bystander effects). This chapter also discusses arterial aging and atherosclerosis, Alzheimer disease and vascular-related dementias, inflammation in obesity, and the processes of normal aging in the absence of specific diseases. The author makes a conclusion that in most chronic diseases of aging, the oxidative stress and inflammation are prominent; moreover, inflammatory changes are observed in many aging tissues even without specific pathology.

Other topics discussed in this book include the role of infections, inflammogens, and drugs in aging process (chapter 2); energy balance, inflammation, and aging (chapter 3); the role of nutrition and infection in the developmental influences on aging (chapter 4); genetics of aging and longevity (chapter 5); evolution of human life span with forecasts for the future (chapter 6).

In my opinion the most interesting part of this book is chapter 4, where the author provides an excellent overview of the Barker hypothesis of fetal origins of adult disease, and expands this hypothesis further to consider the role of early-life infections and inflammation in aging process later in life.

As for technical limitations of this volume, note that some publications cited in text of the book are missing in the Bibliography, and their authors are missing in the Name Index of cited studies too. For example, the following book is discussed three times at page 310:

Gavrilov, L. A., and N. S. Gavrilova. 1991. The Biology of Life Span: A Quantitative Approach. New York: Harwood Academic Publishers. http://tinyurl.com/2am4l3

It would be helpful if this reference be also mentioned in the Bibliography section, and the author's names be included in the Name Index for cited studies too. :)
Less important is a misspelling of a name, when this publication is cited for a second time at page 310 -- (GRavrilov and Gavrilova, 1991) instead of (Gavrilov and Gavrilova, 1991). Perhaps some of these minor suggestions may be useful in a future second print of this interesting book.

See also some interesting excerpts from this book on the links between hibernation, caloric restriction, and life extension.

Have you seen this Book?
Post your comments below!:

Key words:
Aging, Biology of Human Longevity, Caleb Finch, Dietary Restriction, Human Longevity, Infections, Inflammation, Life Span, Nutrition

The abridged and edited version of this book review will be published by the end of year 2007 by this journal:

Quarterly Review of Biology



Home:
Longevity Science Blog
and
The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans
Shorter weblink:
http://tinyurl.com/2rasut

To read further comments on this book, and to post your own thoughts, click here


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