Hi Paul,
Just saw you updated message - well the problems is that there are very few studies that have looked at which supplements can extend the life expectancy of dogs - there is the calorie restriction study (not that hard core actually - 25% fewer calories) and Knoll's Deprenyl study on Beagles (however this was a small scale study and it may be more appropriate at a later stage in the dog's life) - they may be other ones - should any one who read this thead have more information on such studies, please let us know.
Most studies are limited to mouse and other rodents - but this is also what we need to refer too in the lack of more appropriate human studies. From this basis, I think carnosine, ala and alcar are good choices for general anti aging purposes which they have shown in various animals studies- Befotiamine could be another choice - check out a site such as befotiamine.net for for any information on animal studies and maybe asked the guy who runs the site if he knows of any dog studies. Pyridoxamine is another "age inhibitor" - AOR has a branch in Europe which sells a product called Age Amadori which contains both befotiamine and pyridoxamine - you could start with this or find them as cheaper individual products from BAP (powderform) - well depending on shipping fee to the UK. Of other new interesting supplements but we need more info (if available on their benefits and tolerance for dogs) would be e.g. Pomegranate for vascular health (a good source is e.g. Lycopom from newchapter.info) -
Then latter on in his life I would maybe also consider RNA, Ribonucleic Acid Powder - refer again to the other thread and my posts for a link to some positive cases on this supplement. - and maybe one day we and our dogs when they are reaching older age could also use: Algaebrium which is one of the first in a new class of glycation breakers, and has been shown to significantly relax the vascular system, lowering blood pressure. there have been some studies done on dogs (see some reference at end and more general info on
http://morelife.org/...ms/ALT-711.htmlFor "more firm" indications of extending/maximising the life expectancy of animal species there are deprenyl as mentioned above , and I recall that some posters have also mentioned one of the sprin traps PBN as such a candidate on rats but not on houseflies! One of the other spin traps (NtBHA) also has some studies on pubmed concerning its anti aging protection but none as I know specifically on life extension. Maybe one could write to one of the authors and asked if they have an idea of whether it would be beneficial for dogs because it is a quite expensive supplement - If I remember correctly one of the authors on e.g. NtBHA is Bruce Ames who is affiliated with the US firm Juveon which sells a ALA and ALCAR combination.
other sources for information on sprin traps could be Genova, Dr proctor (who has a patent on spin traps) or maybe Paul at morelife.org. Finally someone also mentioned that SODases have shown to extend life in mice - I have not had time yet to find any such supportive studies - good products are SODzyme from LEF and Glisodin made by a French company and commonly used by many other supplement firms.
okay will stop for now - this has already turned into a longer thread :=)
Br
Martin
For more on these studies see a short abstract and reference below:
Ruehl, W. et al (1997) “Treatment with L-deprenyl prolongs life in elderly dogs” Life Sci 61, 1037-44. Ruehl and colleagues performed an experiment with beagle dogs and deprenyl, administered at 1 mg/kg orally per day, for up to 2 years 10 weeks. In a subset of the oldest dogs tested (10-15 years of age), 12 of 15 deprenyl-treated dogs survived to the conclusion of the study, while only 7 of 18 placebo-treated dogs survived. By the time the first deprenyl-treated dog died on day 427 of the study, 5 placebo-treated dogs had already died, the first at day 295.
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. Department of Biology and Institute on Aging, University of South Florida, Tampa 33620, USA.
Accumulating evidence has implicated free radical production and resultant oxidative damage as a major contributing factor in brain aging and cognitive decline. In the present study, aging 24-month-old rats were chronically treated with the synthetic spin-trapping antioxidant phenyl-alpha-tert-butyl nitrone (PBN) for up to 9.5 months. Chronic PBN treatment (1) improved the cognitive performance of aged rats in several tasks, (2) resulted in greater survival during the treatment period, and (3) decreased oxidative damage within brain areas important for cognitive function. These results not only provide a direct linkage between free radicals/oxidative damage and cognitive performance in old age, but also suggest that synthetic brain antioxidants could be developed to treat or prevent age-associated cognitive impairment and Alzheimer's disease.
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. Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275, USA.
N-tert-Butyl-alpha-phenylnitrone (PBN), a lipophilic spin-trapping compound, has been reported to decrease the concentration of protein carbonyls, the products of protein oxidation, in the brain of old gerbils to virtually the level found in the young gerbils (Carney, J. M., et al. (1991) Proc. Natl. Acad. Sci. USA 88, 3633-3636). The validity of this finding as well as that of the commonly used 2,4-dinitrophenylhydrazine procedure for the measurement of protein carbonyls was recently called into question by Cao and Cutler ((1995) Arch. Biochem. Biophys. 320, 106-114). The objective of the present study was to examine some of the relevant issues such as (a) whether the original findings on the effects of PBN can be confirmed, (b) whether similar effects of PBN occur in other species and tissues, and © whether PBN affects the life span of animals. Results of this study provide confirmation of the original finding that PBN indeed causes a decrease in protein carbonyl content in the gerbil brain cortex. However, a similar effect is not observed in the gerbil heart or the mouse brain cortex. Effects of PBN on protein carbonyls are thus variable depending upon tissue and species. PBN administration did not extend the life span of houseflies and at relatively high concentrations it was found to be toxic.
: FASEB J. 2001 Oct;15(12):2196-204. Links
N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria in vivo and in vitro.Atamna H, Robinson C, Ingersoll R, Elliott H, Ames BN.
Department of Molecular and Cell Biology, University of California, Berkeley/CHORI, Oakland, California 94609, USA.
N-t-butyl hydroxylamine (NtBHA) delays senescence-dependent changes in human lung fibroblasts (IMR90) (Atamna et al., J. Biol. Chem. 275, 6741-6748 ). The current study examines the effect of NtBHA on mitochondria in old and young rats and human primary fibroblasts (IMR90). In NtBHA-treated rats, the age-dependent decline in food consumption and ambulatory activity was reversed without affecting body weight. The respiratory control ratio of mitochondria from liver of old rats improved after feeding NtBHA. These findings suggest that NtBHA improved mitochondrial function in vivo. The age-dependent increase in proteins with thiol-mixed disulfides was significantly lower in old rats treated with NtBHA. NtBHA was effective only in old rats; no significant effect was observed in young rats. In IMR90 cells, NtBHA delayed senescence-associated changes in mitochondria and cellular senescence induced by maintaining the cells under suboptimal levels of growth factors. Proteasomal activity was also higher in cells treated with NtBHA than in untreated cells. NtBHA accumulates in cells 10- to 15-fold the extracellular concentration and is maintained by mitochondrial NADH. NtBHA is an antioxidant that is recycled by mitochondrial electron transport chain and prevents radical-induced toxicity to mitochondria.
PMID: 11641246 [PubMed - indexed for MEDLINE]
Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites.Liu J, Atamna H, Kuratsune H, Ames BN.
Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720, USA.
Mitochondria decay with age due to the oxidation of lipids, proteins, RNA, and DNA. Some of this decay can be reversed in aged animals by feeding them the mitochondrial metabolites acetylcarnitine and lipoic acid. In this review, we summarize our recent studies on the effects of these mitochondrial metabolites and mitochondrial antioxidants (alpha-phenyl-N-t-butyl nitrone and N-t-butyl hydroxylamine) on the age-associated mitochondrial decay of the brain of old rats, neuronal cells, and human diploid fibroblast cells. In feeding studies in old rats, these mitochondrial metabolites and antioxidants improve the age-associated decline of ambulatory activity and memory, partially restore mitochondrial structure and function, inhibit the age-associated increase of oxidative damage to lipids, proteins, and nucleic acids, elevate the levels of antioxidants, and restore the activity and substrate binding affinity of a key mitochondrial enzyme, carnitine acetyltransferase. These mitochondrial metabolites and antioxidants protect neuronal cells from neurotoxin- and oxidant-induced toxicity and oxidative damage; delay the normal senescence of human diploid fibroblast cells, and inhibit oxidant-induced acceleration of senescence. These results suggest a plausible mechanism: with age, increased oxidative damage to proteins and lipid membranes, particularly in mitochondria, causes a deformation of structure of enzymes, with a consequent decrease of enzyme activity as well as substrate binding affinity for their substrates; an increased level of substrate restores the velocity of the reaction and restores mitochondrial function, thus delaying mitochondrial decay and aging. This loss of activity due to coenzyme or substrate binding appears to be true for a number of other enzymes as well, including mitochondrial complex III and IV.
PMID: 11976193 [PubMed - indexed for MEDLINE]
On alagebrium (also known as ALT-711)
http://ouroboros.wor...ascular-system/1. John D. Furber Says:
February 15th, 2007 at 9:33 pm
Preclinical research was done on old dogs fed Alagebrium for several weeks. (Asif et al PNAS 14 March 2000) Not only did blood pressure improve, but their aortas were dissected out and their elasticity measured. Elasticity was restored to the large arteries. Alagebrium is NOT just a very good anti-hypertensive drug. It really works, in vivo and in vitro.
1. In an experiment in which 8 aged, but healthy, male mongrel dogs (10.6 ± 0.7 years) received ALT-711 as a gelatin capsule at a single oral daily dose of 1 mg/kg for 4 weeks, there were no changes in fasting blood glucose, hemoglobin A1C, hemoglobin, and creatinine (tested) nor any observable deficits.R
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2809-13
Erratum in: Proc Natl Acad Sci U S A 2000 May 9;97(10):5679
An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness.
Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P, Cerami A, Brines M, Regan TJ.
University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA.
PMID: 10706607
obvious question is whether AGE breakers can also reverse the cardiovascular stiffness associated with normal aging. In this paper, we have evaluated the effect of 4 weeks of daily treatment with the AGE breaker ALT-711 on the stiffness of the left ventricle in diastole in normal aged dogs. The results show that treatment with the AGE cross-link breaker in these aged subjects is associated with a significant reduction of left ventricle chamber stiffness. As a result, cardiac function significantly improves, as evidenced by increased left ventricular (LV) end-diastolic volume (EDV), stroke volume, and decreased end-diastolic pressure (EDP).
Another study:
in 12 dogs, 9-12 yr old....ALT-711 restored LV [left ventricular] ejection fraction, reduced aortic stiffness and LV mass with no reduction in blood glucose level (199 +/- 17 mg/dl), and reversed the upregulation of collagen type I and type III. Myocardial LV collagen solubility (%) increased significantly after treatment with ALT-711. These data suggest that an AGE cross-link breaker may have a therapeutic role in aged patients with DM [diabetes mellitus]."R
Five animals were fed with the cross-link breaker ALT-711 (1 mg/kg) daily for 1 mo before the terminal study.
Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2587-91. Epub 2003 Aug 28.
Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart.
Liu J, Masurekar MR, Vatner DE, Jyothirmayi GN, Regan TJ, Vatner SF, Meggs LG, Malhotra A.
Cardiovascular Research Institute, Dept. of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, PO Box 1709, 185 S. Orange Ave. (MSB G-609 Newark, NJ 07101-1709.
vatnerdo@umdnj.edu
PMID: 12946933
