X-Message-Number: 30192 Date: Fri, 21 Dec 2007 11:28:23 -0800 (PST) From: Subject: Antiaging "drugs" may be available now [Case in point: acetyl-carnitine. Centenarians who take aspirin are already known to experience reduced mortality, as are Japanese centenarians who consume dairy products. I would like to suggest that the time may be fast approaching when a deliberate attempt to extend human as opposed to rodent lifespan may be appropriate. There is enough data out there to make informed decisions on which supplements are likely to extend centenarian lifespan. For example, the negligible serum levels of vitamin D in centenarians points to a severe deficiency of vitamin D in this population. Acetyl-carnitine, lipoic acid, vitamin D, and vitamin K2 are just a few examples of supplements likely to extend human lifespan. The Life Extension Foundation has funded rodent longevity studies in the past without any obvious return on their investment. I would suggest that potential returns would be much higher with the conclusion of a successful Centenarian Life Extension project. With a remaining lifespan of only about 2 years, it would not take long to obtain a successful conclusion to this project, and the potential return would be much higher. Since this would be the first intervention trial in human, as opposed to rodent longevity, this proposed project, if successful would be front page news in every media outlet. Something to think about.] Am J Clin Nutr. 2007 Dec;86(6):1738-44. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Malaguarnera M, Cammalleri L, Gargante MP, Vacante M, Colonna V, Motta M. Department of Senescence, Urological, and Neurological Sciences, University of Catania, Catania, Italy. BACKGROUND: Centenarians are characterized by weakness, decreasing mental health, impaired mobility, and poor endurance. l-Carnitine is an important contributor to cellular energy metabolism. OBJECTIVE: This study evaluated the efficacy of l-carnitine on physical and mental fatigue and on cognitive functions of centenarians. DESIGN: This was a placebo-controlled, randomized, double-blind, 2-phase study. Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study. The 2 groups received either 2 g levocarnitine once daily (n = 32) or placebo (n = 34). Efficacy measures included changes in total fat mass, total muscle mass, serum triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, Mini-Mental State Examination (MMSE), Activities of Daily Living, and a 6-min walking corridor test. RESULTS: At the end of the study period, the levocarnitine-treated centenarians, compared with the placebo group, showed significant improvements in the following markers: total fat mass (-1.80 compared with 0.6 kg; P < 0.01), total muscle mass (3.80 compared with 0.8 kg; P < 0.01), plasma concentrations of total carnitine (12.60 compared with -1.70 mumol; P < 0.05), plasma long-chain acylcarnitine (1.50 compared with -0.1 mumol; P < 0.001), and plasma short-chain acylcarnitine (6.0 compared with -1.50 mumol; P < 0.001). Significant differences were also found in physical fatigue (-4.10 compared with -1.10; P < 0.01), mental fatigue (-2.70 compared with 0.30; P < 0.001), fatigue severity (-23.60 compared with 1.90; P < 0.001), and MMSE (4.1 compared with 0.6; P < 0.001). CONCLUSIONS: Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass, increases total muscular mass, and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions. PMID: 18065594 Arch Gerontol Geriatr. 2007 Jul 19 [Epub ahead of print] Acetyl l-carnitine (ALC) treatment in elderly patients with fatigue. Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M, Koverech A, Neri S, Vacante M, Cammalleri L, Motta M. Centro di Ricerca "La Grande Senescenza", Universit degli Studi di Catania, Via Messina 829, I-95126 Catania, Italy. Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl l-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions. PMID: 17658628 Drugs Aging. 2003;20(10):761-7.Links Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue. Pistone G, Marino A, Leotta C, Dell'Arte S, Finocchiaro G, Malaguarnera M. Department of Senescence, Urological and Neurological Sciences, University of Catania, Catania, Italy. AIM: Levocarnitine is an important contributor to cellular energy metabolism. This study aims to evaluate the effects of levocarnitine supplementation on body composition, lipid profile and fatigue in elderly subjects with rapid muscle fatigue. METHOD: This was a placebo-controlled, randomised, double-blind, two-phase study. Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study. Prior to randomisation all patients entered a 2-week normalisation phase where they were given an 'ad libitum'diet, according to the National Cholesterol Education Program (Step 2). Subjects were asked to record their daily food intake every 2 days. Before the 30-day treatment phase, subjects were randomly assigned to two groups (matched for male/female ratio, age and body mass index). One group received levocarnitine 2g twice daily (n = 42) and the other placebo (n = 42). Efficacy measures included changes in total fat mass, total muscle mass, serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo)A1, and apoB levels. The Wessely and Powell scale was used to evaluate physical and mental fatigue. Subjects were assessed at the beginning and end of the study period. RESULTS: At the end of the study, compared with placebo, the levocarnitine-treated patients showed significant improvements in the following parameters: total fat mass (-3.1 vs -0.5 kg), total muscle mass (+2.1 vs +0.2 kg), total cholesterol (-1.2 vs +0.1 mmol/L), LDL-C (-1.1 vs -0.2 mmol/L), HDL-C (+0.2 vs +0.01 mmol/L), triglycerides (-0.3 vs 0.0 mmol/L), apoA1 (-0.2 vs 0.0 g/L), and apoB (-0.3 vs -0.1 g/L). Wessely and Powell scores decreased significantly by 40% (physical fatigue) and 45% (mental fatigue) in subjects taking levocarnitine, compared with 11% and 8%, respectively, in the placebo group (p < 0.001 vs placebo for both parameters). No adverse events were reported in any treatment group. CONCLUSION: Administration of levocarnitine to healthy elderly subjects resulted in a reduction of total fat mass, an increase of total muscle mass, and appeared to exert a favourable effect on fatigue and serum lipids. PMID: 12875611 Ophthalmologica. 2005 May-Jun;219(3):154-66. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C. Ophthalmic Neuroscience Program, Department of Ophthalmology, University of Rome 'La Sapienza', Rome, Italy. The aim of this randomized, double-blind, placebo-controlled clinical trial was to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus alterations in early age-related macular degeneration (AMD). One hundred and six patients with a clinical diagnosis of early AMD were randomized to the treated or control groups. The primary efficacy variable was the change in the visual field mean defect (VFMD) from baseline to 12 months of treatment, with secondary efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal sensitivity as measured by perimetry, and fundus alterations as evaluated according to the criteria of the International Classification and Grading System for AMD. The mean change in all four parameters of visual functions showed significant improvement in the treated group by the end of the study period. In addition, in the treated group only 1 out of 48 cases (2%) while in the placebo group 9 out of 53 (17%) showed clinically significant (>2.0 dB) worsening in VFMD (p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes was also statistically significant as compared to placebo when either the most affected eyes (p = 0.045) or the less affected eyes (p = 0.017) were considered. These findings strongly suggested that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early AMD. PMID: 15947501 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=30192