Knowledge

Longevity's Relationship to Genetic Signals & Antioxidants

 

LONGEVITY'S RELATIONSHIP TO GENETIC SIGNALS & ANTIOXIDANTS
By: Bill Misner Ph.D.
INTRODUCTION:
The relationship between dietary antioxidants and longevity is argued vigorously and not well understood. Preventing free radical cellular damage and an inevitable premature death using antioxidants is rational. W.B. Grant's and Caldwell Esselstyn's research papers demonstrate that a plant-based antioxidant-rich diet not only prevent pathological disease but in some cases reverses pathology leading to predicted death. Longevity is effected by genetic signals that turn on longevity or conversely turn on apoptosis (cyclic cell death).


During the past two millennia average life expectancy at birth, determined by the chances for death, of humans has risen from 30 years, in ancient Rome, to almost 80 years today in the developed countries. Chances for death are now largely determined by the inherent aging process after age 28. The inherent aging process after age 28 limits life expectancy from birth to around 85 years, but the maximum life span to about 122 years. Modern man has improved survival from birth to age 28 above that of his pre-iron age relatives.

LONGEVITY, as a property of being long-lived, has natural limitations with a strong GENETIC COMPONENT, apparent from research from yeast to humans. Genetic screening efforts with invertebrates have unraveled multiple genetic pathways that imply longevity is promoted through the manipulation of metabolism and the resistance to OXIDATIVE STRESS. Antioxidants versus free radicals may influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. C. elegans and D. melanogaster are important systems for studying aging. This is especially true for the former, in which the age-1 mutant has been shown to greatly increase the life span over the wild-type strain. This genetic mutation results due to increased antioxidative enzyme activities, namely Cu-Zn superoxide dismutase and catalase. Therefore the genomic and free radical theories are very closely linked. Down's syndrome (trisomy 21) is characterized by a significantly shortened life span and also plagued by increased oxidative stress, which results in various free radical-related disturbances. Exactly how this extra chromosome results in an increased production of reactive oxygen species is only partially understood. Not only are several major age-associated diseases clearly affected by increased oxidative stress (atherosclerosis, cancer, parkinson's, multiple sclerosis), but the fact that there are numerous natural protective mechanisms to prevent oxyradical-induced cellular damage speaks loudly that this theory has a key role in aging [the presence of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, among others; various important intrinsic (uric acid, bilirubin, -SH proteins, glutathione, etc.) and extrinsic (vitamins C, E, carotenoids, flavonoids, etc.) antioxidants; and metal chelating proteins to prevent Fenton and Haber-Weiss chemistry]. A major part of the free radical theory involves the damaging role of reactive oxygen species and various toxins on mitochondria. These lead to numerous mitochondrial DNA mutations which result in a progressive reduction in energy output, significantly below that needed in body tissues. This can result in various signs of aging, such as loss of memory, hearing, vision, and stamina. OXIDATIVE STRESS also inactivates critical enzymes and other proteins. Oxidative stress is implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. The beneficial impact of exogenous antioxidants reduces age-related degenerative diseases that may forecast an improvement in life span and enhance quality of life. Reducing free radical damage may reduce vulnerability to pathological disease during "Golden Years." In other words, antioxidants reduce pathology disease's premature mortality toll.

MICRONUTRIENTS DECREASE DURING AGING
There is a decrease in specific microntrients that occur in tandem with increased age. They are: L-carnitine, acetyl-l-carnitine (ALC), creatine phosphate, phenylalanine, s-adenosylmethionine (SAMe), chondroitin sulfate (CSA-B form), ratio of chondroitin sulfate-A (CSA-A) to chondroitin sulfate-C (CSA-C), hyaluronic acid, lutein, stomach hydrochloric acid, cytochrome c oxidase, delta-6 desaturase, glutathione peroxidase, superoxide dismutase (SOD), melatonin, adenosine triphosphate (ATP), docosahexaenoic acid (DHA), phosphatidylcholine, phosphatidylserine (PS), beneficial bacteria (probiotics), bromine, calcium, chromium, copper, iron, magnesium, acetylcholine, nitric oxide, ribonucleic acid (RNA), carnosine, coenzyme CO-Q10, methylsulfonylmethane (MSM), choline, folic acid, lipoic acid, vitamin B1, vitamin C, vitamin B6, vitamin B12, vitamin D, and gamma-tocopherol.

ENDOGENOUS SUBSTANCES DECREASE DURING AGING
There are also an associated decreases in endogenous substances that occur in tandem with increased age. They are: Na-PCA, elastin, norepinephrine, insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF), androstenediol, androstenedione, DHEA (dehydroepiandrosterone), follicle stimulating hormone (FSH), human growth hormone (hGH), luteinizing hormone (LH), pregnenolone, relaxin, testosterone, thymic hormones, thymosin, plasma thymulin, thyroid hormones, and dopamine. .

CONCLUSION:
Consumption of micronutrient antioxidants through food or supplementation reduce free radical oxidation damages to the cells resulting in inhibition of the cell's vulnerability to pathological disease. Several other endogenous substances also decrease with age may have a gene component or a genetic signaling property. This second group of substances may be influenced by diet and supplements. It is proposed that micronutrients and other endogenous substances could be factors in raising the current life expectancy from 85 to the maximum life span to about 122 years. How to reduce free radical damage to cells is currently better understood than how to design dietary protocols that turn off longevity-inhibitor genes or turn on longevity-enhancing genes. .

Hayflick lists the causes of age change:

"Unlike aging, there is no disease or pathology that shares these six qualities":
(a) Occur in every multicellular animal that reaches a fixed size at reproductive maturity
(b) Cross virtually all species barriers
(c) Occur in all members of a species only after the age of reproductive maturation
(d) Occur in all animals removed from the wild and protected by humans even when that species probably has not experienced aging for thousands or even millions of years
(e) Occur in virtually all animate and inanimate matter
(f) Have the same universal molecular etiology, that is, thermodynamic instability

1: Ames BN, Liu J. Delaying the mitochondrial decay of aging with acetylcarnitine. Ann N Y Acad Sci. 2004 Nov;1033:108-16. Review. PMID: 15591008 [PubMed - indexed for MEDLINE

2: Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1876-81. Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184. PMID: 11854488 [PubMed - indexed for MEDLINE]

3: Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci. 2002 Apr;959:133-66. Review. PMID: 11976193 [PubMed - indexed for MEDLINE]

4: Ames BN. Micronutrients prevent cancer and delay aging. Toxicol Lett. 1998 Dec 28;102-103:5-18. Review. PMID: 10022226 [PubMed - indexed for MEDLINE]

5: Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61. Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184-5. PMID: 11854529 [PubMed - indexed for MEDLINE]

6: Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1870-5. Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184. PMID: 11854487 [PubMed - indexed for MEDLINE]

7: Hagen TM, Moreau R, Suh JH, Visioli F. Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann N Y Acad Sci. 2002 Apr;959:491-507. Review. PMID: 11976222 [PubMed - indexed for MEDLINE]

8: Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8. PMID: 9973329 [PubMed - indexed for MEDLINE]

9: Paradies G, Petrosillo G, Gadaleta MN, Ruggiero FM. The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria. FEBS Lett. 1999 Jul 9;454(3):207-9. PMID: 10431808 [PubMed - indexed for MEDLINE]

10: Yasui F, Matsugo S, Ishibashi M, Kajita T, Ezashi Y, Oomura Y, Kojo S, Sasaki K. Effects of chronic acetyl-L-carnitine treatment on brain lipid hydroperoxide level and passive avoidance learning in senescence-accelerated mice. Neurosci Lett. 2002 Dec 16;334(3):177-80. PMID: 12453624 [PubMed - indexed for MEDLINE]

11: Liu J, Head E, Kuratsune H, Cotman CW, Ames BN. Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann N Y Acad Sci. 2004 Nov;1033:117-31. PMID: 15591009 [PubMed - indexed for MEDLINE]

12: Hagen TM, Ingersoll RT, Wehr CM, Lykkesfeldt J, Vinarsky V, Bartholomew JC, Song MH, Ames BN. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9562-6. PMID: 9689120 [PubMed - indexed for MEDLINE]

13: Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr. 2003 May;133(5 Suppl 1):1544S-8S. PMID: 12730462 [PubMed - indexed for MEDLINE]

14: Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS. Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am J Otol. 2000 Mar;21(2):161-7. PMID: 10733178 [PubMed - indexed for MEDLINE]

15: Kaur J, Sharma D, Singh R. Acetyl-L-carnitine enhances Na(+), K(+)-ATPase glutathione-S-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions. Neurosci Lett. 2001 Mar 23;301(1):1-4. PMID: 11239702 [PubMed - indexed for MEDLINE]

16: Hagen TM, Wehr CM, Ames BN. Mitochondrial decay in aging. Reversal through supplementation of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann N Y Acad Sci. 1998 Nov 20;854:214-23. PMID: 9928432 [PubMed - indexed for MEDLINE]

17: Abdul HM, Calabrese V, Calvani M, Butterfield DA. Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. J Neurosci Res. 2006 Aug 1;84(2):398-408. PMID: 16634066 [PubMed - indexed for MEDLINE]

18: Savitha S, Panneerselvam C. Mitochondrial membrane damage during aging process in rat heart: potential efficacy of L-carnitine and DL alpha lipoic acid. Mech Ageing Dev. 2006 Apr;127(4):349-55. Epub 2006 Jan 20. PMID: 16430943 [PubMed - indexed for MEDLINE]

19: Acetyl-L-carnitine. Altern Med Rev. 1999 Dec;4(6):438-41. PMID: 10608918 [PubMed - indexed for MEDLINE]

20: Judge S, Jang YM, Smith A, Hagen T, Leeuwenburgh C. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 2005 Mar;19(3):419-21. Epub 2005 Jan 10. PMID: 15642720 [PubMed - indexed for MEDLINE]

21: Iossa S, Mollica MP, Lionetti L, Crescenzo R, Botta M, Barletta A, Liverini G. Acetyl-L-carnitine supplementation differently influences nutrient partitioning, serum leptin concentration and skeletal muscle mitochondrial respiration in young and old rats. J Nutr. 2002 Apr;132(4):636-42. PMID: 11925454 [PubMed - indexed for MEDLINE]

22: Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, Butterfield DA, Giuffrida Stella AM. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res. 2005 Feb 15;79(4):509-21. PMID: 15641110 [PubMed - indexed for MEDLINE]

23: Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71. PMID: 12598816 [PubMed - indexed for MEDLINE]

24: Paradies G, Ruggiero FM, Petrosillo G, Gadaleta MN, Quagliariello E. Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. Mech Ageing Dev. 1995 Oct 13;84(2):103-12. PMID: 8788238 [PubMed - indexed for MEDLINE]

25: Battino M, Quiles JL, Huertas JR, Mataix JF, Villa RF, Gorini A. Cerebral cortex synaptic heavy mitochondria may represent the oldest synaptic mitochondrial population: biochemical heterogeneity and effects of L-acetylcarnitine. J Bioenerg Biomembr. 2000 Apr;32(2):163-73. PMID: 11768749 [PubMed - indexed for MEDLINE]

26: Calabrese V, Colombrita C, Sultana R, Scapagnini G, Calvani M, Butterfield DA, Stella AM. Redox modulation of heat shock protein expression by acetylcarnitine in aging brain: relationship to antioxidant status and mitochondrial function. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):404-16. PMID: 16677087 [PubMed - indexed for MEDLINE]

27: Aureli T, Di Cocco ME, Capuani G, Ricciolini R, Manetti C, Miccheli A, Conti F. Effect of long-term feeding with acetyl-L-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy. Neurochem Res. 2000 Mar;25(3):395-9. PMID: 10761985 [PubMed - indexed for MEDLINE]

28: Liu J, Ames BN. Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease. Nutr Neurosci. 2005 Apr;8(2):67-89. Review. PMID: 16053240 [PubMed - indexed for MEDLINE]

29: Traina G, Bernardi R, Rizzo M, Calvani M, Durante M, Brunelli M. Acetyl-L-carnitine up-regulates expression of voltage-dependent anion channel in the rat brain. Neurochem Int. 2006 Jun;48(8):673-8. Epub 2006 Mar 9. PMID: 16527372 [PubMed - indexed for MEDLINE]

30: Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10771-8. Review. PMID: 7971961 [PubMed - indexed for MEDLINE]

31: Villa RF, Turpeenoja L, Benzi G, Giuffrida Stella AM. Action of L-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum. Neurochem Res. 1988 Oct;13(10):909-16. PMID: 3216947 [PubMed - indexed for MEDLINE]

32: Carta A, Calvani M, Bravi D, Bhuachalla SN. Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere. Ann N Y Acad Sci. 1993 Sep 24;695:324-6. Review. PMID: 8239306 [PubMed - indexed for MEDLINE]

33: Muthuswamy AD, Vedagiri K, Ganesan M, Chinnakannu P. Oxidative stress-mediated macromolecular damage and dwindle in antioxidant status in aged rat brain regions: role of L-carnitine and DL-alpha-lipoic acid. Clin Chim Acta. 2006 Jun;368(1-2):84-92. Epub 2006 Feb 15. PMID: 16480704 [PubMed - indexed for MEDLINE]

34: Paradies G, Ruggiero FM, Gadaleta MN, Quagliariello E. The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochim Biophys Acta. 1992 Jan 31;1103(2):324-6. PMID: 1543717 [PubMed - indexed for MEDLINE]

35: Villa RF, Gorini A, Zanada F, Benzi G. Action of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus. Arch Int Pharmacodyn Ther. 1986 Feb;279(2):195-211. PMID: 3963936 [PubMed - indexed for MEDLINE]

36: Kumaran S, Panneerselvam KS, Shila S, Sivarajan K, Panneerselvam C. Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: role of carnitine and lipoic acid. Mol Cell Biochem. 2005 Dec;280(1-2):83-9. PMID: 16311908 [PubMed - indexed for MEDLINE]

37: Ghirardi O, Milano S, Ramacci MT, Angelucci L. Effect of acetyl-l-carnitine chronic treatment on discrimination models in aged rats. Physiol Behav. 1988;44(6):769-73. PMID: 3249750 [PubMed - indexed for MEDLINE]

38: Poon HF, Calabrese V, Calvani M, Butterfield DA. Proteomics analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by L-acetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative stress. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):381-94. PMID: 16677085 [PubMed - indexed for MEDLINE]

39: Ames BN, Shigenaga MK, Hagen TM. Mitochondrial decay in aging. Biochim Biophys Acta. 1995 May 24;1271(1):165-70. Review. PMID: 7599204 [PubMed - indexed for MEDLINE]

40: Mollica MP, Iossa S, Soboll S, Liverini G. Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats. Cell Mol Life Sci. 2001 Mar;58(3):477-84. PMID: 11315193 [PubMed - indexed for MEDLINE]

41: Novikov VE, Kovaleva LA. [The effect of nootropic agents on brain mitochondrial function in the dynamics of craniocerebral trauma from the age aspect] Eksp Klin Farmakol. 1998 Mar-Apr;61(2):65-8. Russian. PMID: 9621180 [PubMed - indexed for MEDLINE]

42: Gadaleta MN, Petruzzella V, Renis M, Fracasso F, Cantatore P. Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem. 1990 Feb 14;187(3):501-6. PMID: 2154375 [PubMed - indexed for MEDLINE]

43: Carta A, Calvani M. Acetyl-L-carnitine: a drug able to slow the progress of Alzheimer's disease? Ann N Y Acad Sci. 1991;640:228-32. PMID: 1776743 [PubMed - indexed for MEDLINE]

44: Picconi B, Barone I, Pisani A, Nicolai R, Benatti P, Bernardi G, Calvani M, Calabresi P. Acetyl-L-carnitine protects striatal neurons against in vitro ischemia: the role of endogenous acetylcholine. Neuropharmacology. 2006 Jun;50(8):917-23. Epub 2006 Feb 24. PMID: 16500685 [PubMed - indexed for MEDLINE]

45: Lopez-Arrieta JM, Schneider L. Metrifonate for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003155. Review. PMID: 16625573 [PubMed - indexed for MEDLINE]

46: Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001747. Review. PMID: 16437436 [PubMed - indexed for MEDLINE]

47: Traina G, Valleggi S, Bernardi R, Rizzo M, Calvani M, Nicolai R, Mosconi L, Durante M, Brunelli M. Identification of differentially expressed genes induced in the rat brain by acetyl-L-carnitine as evidenced by suppression subtractive hybridisation. Brain Res Mol Brain Res. 2004 Dec 6;132(1):57-63. PMID: 15548429 [PubMed - indexed for MEDLINE]

48: Panneerselvam KS, Kumaran S. l-Carnitine and alpha-lipoic acid improves mitochondrial function during ageing process. Clin Nutr. 2006 May 9; [Epub ahead of print] PMID: 16690174 [PubMed - as supplied by publisher]

49: Kohjimoto Y, Ogawa T, Matsumoto M, Shirakawa K, Kuwaki T, Yasuda H, Anami K, Fujii T, Satoh H, Ono T. Effects of acetyl-L-carnitine on the brain lipofuscin content and emotional behavior in aged rats. Jpn J Pharmacol. 1988 Nov;48(3):365-71. PMID: 3221536 [PubMed - indexed for MEDLINE]

50: Virmani A, Gaetani F, Binienda Z, Xu A, Duhart H, Ali SF. Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine. Ann N Y Acad Sci. 2004 Oct;1025:267-73. PMID: 15542726 [PubMed - indexed for MEDLINE]

51: Gadaleta MN, Petruzzella V, Daddabbo L, Olivieri C, Fracasso F, Loguercio Polosa P, Cantatore P. Mitochondrial DNA transcription and translation in aged rat. Effect of acetyl-L-carnitine. Ann N Y Acad Sci. 1994 Jun 30;717:150-60. No abstract available. PMID: 7518198 [PubMed - indexed for MEDLINE]

52: Paradies G, Ruggiero FM, Petrosillo G, Gadaleta MN, Quagliariello E. Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. FEBS Lett. 1994 Aug 22;350(2-3):213-5. PMID: 8070566 [PubMed - indexed for MEDLINE]

53: Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. Review. PMID: 16437532 [PubMed - indexed for MEDLINE]

54: Atamna H, Robinson C, Ingersoll R, Elliott H, Ames BN. N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria in vivo and in vitro. FASEB J. 2001 Oct;15(12):2196-204. PMID: 11641246 [PubMed - indexed for MEDLINE]

55: Hagen TM, Yowe DL, Bartholomew JC, Wehr CM, Do KL, Park JY, Ames BN. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3064-9. PMID: 9096346 [PubMed - indexed for MEDLINE]

56: Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001190. Review. PMID: 16437430 [PubMed - indexed for MEDLINE]

57: Poon HF, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE, Klein JB, Butterfield DA. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders. Neurochem Int. 2005 Jan;46(2):159-68. PMID: 15627516 [PubMed - indexed for MEDLINE]

58: Anbarasi K, Vani G, Devi CS. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats. J Environ Pathol Toxicol Oncol. 2005;24(3):225-34. PMID: 16050806 [PubMed - indexed for MEDLINE]

59: Manczak M, Jung Y, Park BS, Partovi D, Reddy PH. Time-course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging. J Neurochem. 2005 Feb;92(3):494-504. PMID: 15659220 [PubMed - indexed for MEDLINE]

60: Ames BN. Delaying the mitochondrial decay of aging. Ann N Y Acad Sci. 2004 Jun;1019:406-11. Review. PMID: 15247055 [PubMed - indexed for MEDLINE]

61: Ricci A, Ramacci MT, Ghirardi O, Amenta F. Age-related changes of the mossy fibre system in rat hippocampus: effect of long term acetyl-L-carnitine treatment. Arch Gerontol Geriatr. 1989 Jan;8(1):63-71. PMID: 2712650 [PubMed - indexed for MEDLINE]

62: Calabrese V, Giuffrida Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem. 2006 Feb;17(2):73-88. Epub 2005 Oct 18. Review. PMID: 16413418 [PubMed - indexed for MEDLINE]

63: Johannsen P, Salmon E, Hampel H, Xu Y, Richardson S, Qvitzau S, Schindler R; AWARE Study Group. Assessing therapeutic efficacy in a progressive disease: a study of donepezil in Alzheimer's disease. CNS Drugs. 2006;20(4):311-25. Erratum in: CNS Drugs. 2006;20(10):866. PMID: 16599649 [PubMed - indexed for MEDLINE]

64: Mansour HH. Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol Res. 2006 Sep;54(3):165-71. Epub 2006 May 1. PMID: 16757176 [PubMed - indexed for MEDLINE]

65: Hao Y, Basile AS, Chen G, Zhang L. Glutamate-induced over-expression of GAD is down-regulated by acetyl-L-carnitine in rat islet cells. Endocr Res. 2004 Feb;30(1):107-16. PMID: 15098924 [PubMed - indexed for MEDLINE]

66: Long J, Wang X, Gao H, Liu Z, Liu C, Miao M, Liu J. Malonaldehyde acts as a mitochondrial toxin: Inhibitory effects on respiratory function and enzyme activities in isolated rat liver mitochondria. Life Sci. 2006 Sep 5;79(15):1466-72. Epub 2006 May 7. PMID: 16737718 [PubMed - indexed for MEDLINE]

67: Sethumadhavan S, Chinnakannu P. Carnitine and lipoic acid alleviates protein oxidation in heart mitochondria during aging process. Biogerontology. 2006 Apr;7(2):101-9. PMID: 16802113 [PubMed - indexed for MEDLINE]

68: Lesnefsky EJ, He D, Moghaddas S, Hoppel CL. Reversal of mitochondrial defects before ischemia protects the aged heart. FASEB J. 2006 Jul;20(9):1543-5. Epub 2006 Jun 22. PMID: 16793872 [PubMed - indexed for MEDLINE]

69: Fregonesi CE, Molinari SL, Alves AM, Defani MA, Zanoni JN, Bazotte RB, de Miranda Neto MH. Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-L-carnitine. Anat Histol Embryol. 2005 Apr;34(2):93-7. PMID: 15771670 [PubMed - indexed for MEDLINE]

70: Savitha S, Tamilselvan J, Anusuyadevi M, Panneerselvam C. Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of DL-alpha-lipoic acid and L-carnitine. Clin Chim Acta. 2005 May;355(1-2):173-80. PMID: 15820492 [PubMed - indexed for MEDLINE]

71: Butterfield DA, Rangachari A. Acetylcarnitine increases membrane cytoskeletal protein-protein interactions. Life Sci. 1993;52(3):297-303. PMID: 8380879 [PubMed - indexed for MEDLINE]

72: Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C. Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging. Clin Nutr. 2005 Oct;24(5):794-800. PMID: 15919137 [PubMed - indexed for MEDLINE]

73: Poon HF, Shepherd HM, Reed TT, Calabrese V, Stella AM, Pennisi G, Cai J, Pierce WM, Klein JB, Butterfield DA. Proteomics analysis provides insight into caloric restriction mediated oxidation and expression of brain proteins associated with age-related impaired cellular processes: Mitochondrial dysfunction, glutamate dysregulation and impaired protein synthesis. Neurobiol Aging. 2006 Jul;27(7):1020-34. Epub 2005 Jul 5. PMID: 15996793 [PubMed - indexed for MEDLINE]

74: Moreira PI, Santos MS, Sena C, Seica R, Oliveira CR. Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol Dis. 2005 Apr;18(3):628-37. PMID: 15755688 [PubMed - indexed for MEDLINE]

75: Wong YT, Ruan R, Tay FE. Relationship between levels of oxidative DNA damage, lipid peroxidation and mitochondrial membrane potential in young and old F344 rats. Free Radic Res. 2006 Apr;40(4):393-402. PMID: 16517504 [PubMed - indexed for MEDLINE]

76: Defani MA, Zanoni JN, Natali MR, Bazotte RB, de Miranda-Neto MH. Effect of acetyl-L-carnitine on VIP-ergic neurons in the jejunum submucous plexus of diabetic rats. Arq Neuropsiquiatr. 2003 Dec;61(4):962-7. Epub 2004 Jan 6. PMID: 14762599 [PubMed - indexed for MEDLINE]

77: Suh GH, Yeon Jung H, Uk Lee C, Hoon Oh B, Nam Bae J, Jung HY, Ju YS, Kil Yeon B, Park J, Hong I, Choi S, Ho Lee J; Korean Galantamine Study Group. A prospective, double-blind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population. Clin Ther. 2004 Oct;26(10):1608-18. PMID: 15598477 [PubMed - indexed for MEDLINE]

78: Juliet PA, Joyee AG, Jayaraman G, Mohankumar MN, Panneerselvam C. Effect of L-carnitine on nucleic acid status of aged rat brain. Exp Neurol. 2005 Jan;191(1):33-40. PMID: 15589510 [PubMed - indexed for MEDLINE]

79: Ames BN. A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys. 2004 Mar 1;423(1):227-34. Review. PMID: 14989256 [PubMed - indexed for MEDLINE]

80: Servais S, Boussouar A, Molnar A, Douki T, Pequignot JM, Favier R. Age-related sensitivity to lung oxidative stress during ozone exposure. Free Radic Res. 2005 Mar;39(3):305-16. PMID: 15788235 [PubMed - indexed for MEDLINE]

81: Cassano P, Sciancalepore AG, Pesce V, Fluck M, Hoppeler H, Calvani M, Mosconi L, Cantatore P, Gadaleta MN. Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis. Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1421-8. Epub 2006 May 19. PMID: 16814248 [PubMed - indexed for MEDLINE]

82: Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10(1):52-60. PMID: 15829111 [PubMed - indexed for MEDLINE]

83: Hino K, Nishikawa M, Sato E, Inoue M. L-carnitine inhibits hypoglycemia-induced brain damage in the rat. Brain Res. 2005 Aug 16;1053(1-2):77-87. PMID: 16051203 [PubMed - indexed for MEDLINE]

84: Sethumadhavan S, Chinnakannu P. L-carnitine and alpha-lipoic acid improve age-associated decline in mitochondrial respiratory chain activity of rat heart muscle. J Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):650-9. PMID: 16870625 [PubMed - indexed for MEDLINE]

85: Zanelli SA, Solenski NJ, Rosenthal RE, Fiskum G. Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann N Y Acad Sci. 2005 Aug;1053:153-61. Review. PMID: 16179519 [PubMed - indexed for MEDLINE]

86: Fukui K, Takatsu H, Shinkai T, Suzuki S, Abe K, Urano S. Appearance of amyloid beta-like substances and delayed-type apoptosis in rat hippocampus CA1 region through aging and oxidative stress. J Alzheimers Dis. 2005 Dec;8(3):299-309. PMID: 16340088 [PubMed - indexed for MEDLINE]

87: Bodis-Wollner I. Physiological effects of acetyl-levo-carnitine in the central nervous system. Int J Clin Pharmacol Res. 1990;10(1-2):109-14. Review. PMID: 2201653 [PubMed - indexed for MEDLINE]

88: Ng Y, Barhoumi R, Tjalkens RB, Fan YY, Kolar S, Wang N, Lupton JR, Chapkin RS. The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis. 2005 Nov;26(11):1914-21. Epub 2005 Jun 23. PMID: 15975958 [PubMed - indexed for MEDLINE]

89: Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ; Alzheimer's Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005 Jun 9;352(23):2379-88. Epub 2005 Apr 13. PMID: 15829527 [PubMed - indexed for MEDLINE]

90: Sen T, Sen N, Tripathi G, Chatterjee U, Chakrabarti S. Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria. Neurochem Int. 2006 Jul;49(1):20-7. Epub 2006 Feb 28. PMID: 16510213 [PubMed - indexed for MEDLINE]

91: Pesce V, Fracasso F, Musicco C, Lezza AM, Cantatore P, Gadaleta MN. Acetyl-L-carnitine dietary supplementation to old rats increases mitochondrial transcription factor A content in rat hindlimb skeletal muscles. Ann N Y Acad Sci. 2004 Jun;1019:430-3. PMID: 15247059 [PubMed - indexed for MEDLINE]

92: Opii WO, Joshi G, Head E, Milgram NW, Muggenburg BA, Klein JB, Pierce WM, Cotman CW, Butterfield DA. Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease. Neurobiol Aging. 2006 Oct 19; [Epub ahead of print] PMID: 17055614 [PubMed - as supplied by publisher] 93: Guang HM, Du GH. Protections of pinocembrin on brain mitochondria contribute to cognitive improvement in chronic cerebral hypoperfused rats. Eur J Pharmacol. 2006 Aug 7;542(1-3):77-83. Epub 2006 May 12. PMID: 16806158 [PubMed - indexed for MEDLINE]

94: Sanz A, Caro P, Ibanez J, Gomez J, Gredilla R, Barja G. Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. J Bioenerg Biomembr. 2005 Apr;37(2):83-90. PMID: 15906153 [PubMed - indexed for MEDLINE]

95: Cocco T, Sgobbo P, Clemente M, Lopriore B, Grattagliano I, Di Paola M, Villani G. Tissue-specific changes of mitochondrial functions in aged rats: effect of a long-term dietary treatment with N-acetylcysteine. Free Radic Biol Med. 2005 Mar 15;38(6):796-805. PMID: 15721990 [PubMed - indexed for MEDLINE]

96: Giuliani A, Capuani G, Miccheli A, Aureli T, Ramacc MT, Conti F. Multivariate data analysis in biochemistry: a new integrative approach to metabolic control in brain aging. Cell Mol Biol. 1991;37(6):631-8. PMID: 1747898 [PubMed - indexed for MEDLINE]

97: Marini G, Calvani M, Ceccarelli P, Mancia M. Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats. Arch Ital Biol. 2006 Feb;144(1):33-43. PMID: 16425616 [PubMed - indexed for MEDLINE]

98: Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, Brownlee M, Monnier VM, Weiss MF. Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol. 2005 Aug;289(2):F420-30. Epub 2005 Apr 5. PMID: 15814529 [PubMed - indexed for MEDLINE]

99: Kolosova NG, Shcheglova TV, Sergeeva SV, Loskutova LV. Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats. Neurobiol Aging. 2006 Sep;27(9):1289-97. Epub 2005 Oct 24. PMID: 16246464 [PubMed - indexed for MEDLINE]

100: Schuessel K, Frey C, Jourdan C, Keil U, Weber CC, Muller-Spahn F, Muller WE, Eckert A. Aging sensitizes toward ROS formation and lipid peroxidation in PS1M146L transgenic mice. Free Radic Biol Med. 2006 Mar 1;40(5):850-62. Epub 2005 Nov 15. PMID: 16520237 [PubMed - indexed for MEDLINE]

101: Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P. Beneficial effects of DL-alpha-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis. Chem Biol Interact. 2005 Feb 28;152(1):59-66. PMID: 15766923 [PubMed - indexed for MEDLINE]

102: Kim HJ, Nel AE. The role of phase II antioxidant enzymes in protecting memory T cells from spontaneous apoptosis in young and old mice. J Immunol. 2005 Sep 1;175(5):2948-59. PMID: 16116181 [PubMed - indexed for MEDLINE]

103: Haripriya D, Sangeetha P, Kanchana A, Balu M, Panneerselvam C. Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex, striatum and hippocampus by L-carnitine. Exp Gerontol. 2005 Mar;40(3):129-35. Epub 2004 Nov 11. PMID: 15763389 [PubMed - indexed for MEDLINE]

104: Sundaram K, Panneerselvam KS. Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats: role of carnitine and lipoicacid. Biogerontology. 2006 Apr;7(2):111-8. PMID: 16802114 [PubMed - indexed for MEDLINE]

105: Haripriya D, Devi MA, Kokilavani V, Sangeetha P, Panneerselvam C. Age-dependent alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain -- potential role of L-Carnitine. Biogerontology. 2004;5(5):355-64. PMID: 15547323 [PubMed - indexed for MEDLINE]

106: Fattoretti P, Bertoni-Freddari C, Giorgetti B, Balietti M. Increased mitochondrial and nuclear gene expression of cytochrome oxidase subunits I and IV in neuronal aging. Ann N Y Acad Sci. 2004 Dec;1030:303-9. PMID: 15659811 [PubMed - indexed for MEDLINE]

107: Muller WE, Eckert GP, Eckert A. Piracetam: novelty in a unique mode of action. Pharmacopsychiatry. 1999 Mar;32 Suppl 1:2-9. Review. PMID: 10338102 [PubMed - indexed for MEDLINE]

108: Ames BN. Mitochondrial decay, a major cause of aging, can be delayed. J Alzheimers Dis. 2004 Apr;6(2):117-21. PMID: 15096694 [PubMed - indexed for MEDLINE]

109: Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH. Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet. 2006 May 1;15(9):1437-49. Epub 2006 Mar 21. PMID: 16551656 [PubMed - indexed for MEDLINE]

110: Devi CB, Reddy GH, Prasanthi RP, Chetty CS, Reddy GR. Developmental lead exposure alters mitochondrial monoamine oxidase and synaptosomal catecholamine levels in rat brain. Int J Dev Neurosci. 2005 Jun;23(4):375-81. PMID: 15927761 [PubMed - indexed for MEDLINE]

111: Tkachenko HM, Kurhaliuk NM, Vovkanych LS. [Effect of K-ATP channel opener-pinacidil on the liver mitochondria function in rats with different resistance to hypoxia during stress] Ukr Biokhim Zh. 2004 Jan-Feb;76(1):56-64. Ukrainian. PMID: 15909418 [PubMed - indexed for MEDLINE]

112: Corbucci GG, Melis A, Piga M, Marchionni A, Calvani M. Influence of acetyl-carnitine on some mitochondrial enzymic activities in the human cerebral tissue in conditions of acute hypoxia. Int J Tissue React. 1992;14(4):183-94. PMID: 1478796 [PubMed - indexed for MEDLINE]

113: Anantharaman M, Tangpong J, Keller JN, Murphy MP, Markesbery WR, Kiningham KK, St Clair DK. Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease. Am J Pathol. 2006 May;168(5):1608-18. PMID: 16651627 [PubMed - indexed for MEDLINE]

114: Reiser G, Schonfeld P, Kahlert S. Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment. Int J Dev Neurosci. 2006 Apr-May;24(2-3):113-22. Epub 2006 Jan 18. PMID: 16386870 [PubMed - indexed for MEDLINE]

115: Levey A, Lah J, Goldstein F, Steenland K, Bliwise D. Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease. Clin Ther. 2006 Jul;28(7):991-1001. Review. PMID: 16990077 [PubMed - indexed for MEDLINE]

116: Gorini A, Ghigini B, Villa RF. Acetylcholinesterase activity of synaptic plasma membranes during ageing: effect of L-acetylcarnitine. Dementia. 1996 May-Jun;7(3):147-54. PMID: 8740629 [PubMed - indexed for MEDLINE]

117: Kiray M, Bagriyanik HA, Pekcetin C, Ergur BU, Uysal N, Ozyurt D, Buldan Z. Deprenyl and the relationship between its effects on spatial memory, oxidant stress and hippocampal neurons in aged male rats. Physiol Res. 2006;55(2):205-12. Epub 2005 May 24. PMID: 15910165 [PubMed - indexed for MEDLINE]

118: Disterhoft JF, Oh MM. Pharmacological and molecular enhancement of learning in aging and Alzheimer's disease. J Physiol Paris. 2006 Mar-May;99(2-3):180-92. Epub 2006 Feb 3. Review. PMID: 16458491 [PubMed - indexed for MEDLINE]

119: Shila S, Subathra M, Devi MA, Panneerselvam C. Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid. Arch Toxicol. 2005 Mar;79(3):140-6. Epub 2004 Nov 11. PMID: 15798887 [PubMed - indexed for MEDLINE]

120: Butterfield DA, Reed T, Perluigi M, De Marco C, Coccia R, Cini C, Sultana R. Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci Lett. 2006 Apr 24;397(3):170-3. Epub 2006 Jan 4. PMID: 16413966 [PubMed - indexed for MEDLINE]

121: Jimenez-Jimenez FJ, Alonso-Navarro H, Ayuso-Peralta L, Jabbour-Wadih T. [Oxidative stress and Alzheimer's disease] Rev Neurol. 2006 Apr 1-15;42(7):419-27. Review. Spanish. PMID: 16602059 [PubMed - indexed for MEDLINE]

122: Jin Y, McEwen ML, Nottingham SA, Maragos WF, Dragicevic NB, Sullivan PG, Springer JE. The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord. J Neurotrauma. 2004 Oct;21(10):1396-404. PMID: 15672630 [PubMed - indexed for MEDLINE]

123: Wang XJ, Wang ZB, Xu JX. Effect of salvianic acid A on lipid peroxidation and membrane permeability in mitochondria. J Ethnopharmacol. 2005 Mar 21;97(3):441-5. PMID: 15740878 [PubMed - indexed for MEDLINE]

124: Craig D, Birks J. Galantamine for vascular cognitive impairment. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004746. Review. PMID: 16437493 [PubMed - indexed for MEDLINE]

125: Mansouri A, Muller FL, Liu Y, Ng R, Faulkner J, Hamilton M, Richardson A, Huang TT, Epstein CJ, Van Remmen H. Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging. Mech Ageing Dev. 2006 Mar;127(3):298-306. Epub 2006 Jan 6. PMID: 16405961 [PubMed - indexed for MEDLINE]

126: Perumal SS, Shanthi P, Sachdanandam P. Augmented efficacy of tamoxifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and CoQ10: effects on lipid peroxidation and antioxidants in mitochondria. Chem Biol Interact. 2005 Feb 28;152(1):49-58. PMID: 15766922 [PubMed - indexed for MEDLINE]

127: Shila S, Kokilavani V, Subathra M, Panneerselvam C. Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat. Toxicology. 2005 May 15;210(1):25-36. PMID: 15804455 [PubMed - indexed for MEDLINE]

128: Tokita K, Inoue T, Yamazaki S, Wang F, Yamaji T, Matsuoka N, Mutoh S. FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats. Eur J Pharmacol. 2005 Dec 19;527(1-3):111-20. PMID: 16325809 [PubMed - indexed for MEDLINE]

129: Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, Ahmad AS, Islam F. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res. 2006 Jul 15;171(1):9-16. Epub 2006 Apr 18. PMID: 16621054 [PubMed - indexed for MEDLINE]

130: Kakarla P, Vadluri G, Reddy Kesireddy S. Response of hepatic antioxidant system to exercise training in aging female rat. J Exp Zoolog A Comp Exp Biol. 2005 Mar 1;303(3):203-8. PMID: 15726629 [PubMed - indexed for MEDLINE]

131: Oxenkrug G. Antioxidant effects of N-acetylserotonin: possible mechanisms and clinical implications. Ann N Y Acad Sci. 2005 Aug;1053:334-47. PMID: 16179540 [PubMed - indexed for MEDLINE]

132: Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease. J Neurochem. 2005 May;93(4):953-62. PMID: 15857398 [PubMed - indexed for MEDLINE]

133: Day L, Shikuma C, Gerschenson M. Acetyl-L-carnitine for the treatment of HIV lipoatrophy. Ann N Y Acad Sci. 2004 Nov;1033:139-46. Review. PMID: 15591011 [PubMed - indexed for MEDLINE]

134: Kidd PM. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev. 2005 Dec;10(4):268-93. Review. PMID: 16366737 [PubMed - indexed for MEDLINE]

135: Siqueira IR, Fochesatto C, de Andrade A, Santos M, Hagen M, Bello-Klein A, Netto CA. Total antioxidant capacity is impaired in different structures from aged rat brain. Int J Dev Neurosci. 2005 Dec;23(8):663-71. Epub 2005 Nov 17. PMID: 16298100 [PubMed - indexed for MEDLINE]

136: Li Y, Qin HQ, Chen QS, Wang JJ. Neurochemical and behavioral effects of the intrahippocampal co-injection of beta-amyloid protein1-40 and ibotenic acid in rats. Life Sci. 2005 Jan 28;76(11):1189-97. Epub 2004 Dec 8. PMID: 15642590 [PubMed - indexed for MEDLINE]

137: Hadi AH, Abdolamir A, Mahtab H, Abolfazl D, Yusef R. Influence of plasma total antioxidant ability on lipid and protein oxidation products in plasma and erythrocyte ghost obtained from developing and adult rats pretreated with two vitamin K formulations. Mol Cell Biochem. 2004 Dec;267(1-2):195-201. PMID: 15663201 [PubMed - indexed for MEDLINE]

138: Mishra OP, Randis T, Ashraf QM, Delivoria-Papadopoulos M. Hypoxia-induced Bax and Bcl-2 protein expression, caspase-9 activation, DNA fragmentation, and lipid peroxidation in mitochondria of the cerebral cortex of newborn piglets: the role of nitric oxide. Neuroscience. 2006 Sep 1;141(3):1339-49. Epub 2006 Jun 13. PMID: 16777344 [PubMed - indexed for MEDLINE]

139: Joshi H, Parle M. Evaluation of nootropic potential of Ocimum sanctum Linn. in mice. Indian J Exp Biol. 2006 Feb;44(2):133-6. PMID: 16480180 [PubMed - indexed for MEDLINE]

140: Sorensen M, Sanz A, Gomez J, Pamplona R, Portero-Otin M, Gredilla R, Barja G. Effects of fasting on oxidative stress in rat liver mitochondria. Free Radic Res. 2006 Apr;40(4):339-47. PMID: 16517498 [PubMed - indexed for MEDLINE]

141: Sinitsyna O, Krysanova Z, Ishchenko A, Dikalova AE, Stolyarov S, Kolosova N, Vasunina E, Nevinsky G. Age-associated changes in oxidative damage and the activity of antioxidant enzymes in rats with inherited overgeneration of free radicals. J Cell Mol Med. 2006 Jan-Mar;10(1):206-15. PMID: 16563232 [PubMed - indexed for MEDLINE]

142: Perez-De La Cruz V, Gonzalez-Cortes C, Galvan-Arzate S, Medina-Campos ON, Perez-Severiano F, Ali SF, Pedraza-Chaverri J, Santamaria A. Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III). Neuroscience. 2005;135(2):463-74. PMID: 16111817 [PubMed - indexed for MEDLINE]

143: Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, Packer L, Liu J. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. J Neurosci Res. 2006 Aug 15;84(3):647-54. PMID: 16710848 [PubMed - indexed for MEDLINE]

144: McGuinness B, Todd S, Passmore P, Bullock R. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004034. Review. PMID: 16625595 [PubMed - indexed for MEDLINE]

145: Celik I, Tuluce Y, Isik I. Influence of subacute treatment of some plant growth regulators on serum marker enzymes and erythrocyte and tissue antioxidant defense and lipid peroxidation in rats. J Biochem Mol Toxicol. 2006;20(4):174-82. PMID: 16906522 [PubMed - in process] 146: Youdim MB, Buccafusco JJ. CNS Targets for multi-functional drugs in the treatment of Alzheimer's and Parkinson's diseases. J Neural Transm. 2005 Apr;112(4):519-37. Epub 2005 Jan 24. Review. PMID: 15666041 [PubMed - indexed for MEDLINE]

147: Sima AA, Calvani M, Mehra M, Amato A; Acetyl-L-Carnitine Study Group. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care. 2005 Jan;28(1):89-94. PMID: 15616239 [PubMed - indexed for MEDLINE]

148: Hagen JL, Krause DJ, Baker DJ, Fu MH, Tarnopolsky MA, Hepple RT. Skeletal muscle aging in F344BN F1-hybrid rats: I. Mitochondrial dysfunction contributes to the age-associated reduction in VO2max. J Gerontol A Biol Sci Med Sci. 2004 Nov;59(11):1099-110. PMID: 15602055 [PubMed - indexed for MEDLINE]

149: Khan FH, Sen T, Maiti AK, Jana S, Chatterjee U, Chakrabarti S. Inhibition of rat brain mitochondrial electron transport chain activity by dopamine oxidation products during extended in vitro incubation: implications for Parkinson's disease. Biochim Biophys Acta. 2005 Jun 30;1741(1-2):65-74. Epub 2005 Apr 14. PMID: 15925494 [PubMed - indexed for MEDLINE]

150: Qiao X, Chen X, Wu D, Ding R, Wang J, Hong Q, Shi S, Li J, Xie Y, Lu Y, Wang Z. Mitochondrial pathway is responsible for aging-related increase of tubular cell apoptosis in renal ischemia/reperfusion injury. J Gerontol A Biol Sci Med Sci. 2005 Jul;60(7):830-9. PMID: 16079204 [PubMed - indexed for MEDLINE]

151: Moreira PI, Santos MS, Sena C, Nunes E, Seica R, Oliveira CR. CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats. Exp Neurol. 2005 Nov;196(1):112-9. Epub 2005 Aug 29. PMID: 16126199 [PubMed - indexed for MEDLINE]

152: Mohmmad Abdul H, Sultana R, Keller JN, St Clair DK, Markesbery WR, Butterfield DA. Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. J Neurochem. 2006 Mar;96(5):1322-35. PMID: 16478525 [PubMed - indexed for MEDLINE]

153: Acharya MM, Katyare SS. Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain. Exp Neurol. 2005 Mar;192(1):79-88. Erratum in: Exp Neurol. 2005 Aug;194(2):560. PMID: 15698621 [PubMed - indexed for MEDLINE]

154: Novikov VE, Kovaleva LA. [The effect of substances with nootropic activity on oxidative phosphorylation in brain mitochondria in acute craniocerebral trauma] Eksp Klin Farmakol. 1997 Jan-Feb;60(1):59-61. Russian. PMID: 9162289 [PubMed - indexed for MEDLINE]

155: Bertoni-Freddari C, Fattoretti P, Giorgetti B, Solazzi M, Balietti M, Di Stefano G, Casoli T. Decay of mitochondrial metabolic competence in the aging cerebellum. Ann N Y Acad Sci. 2004 Jun;1019:29-32. Review. PMID: 15246988 [PubMed - indexed for MEDLINE]

156: Belostotskaia LI, Chaika LA, Gomon ON. [Effect of cinnarizine on the brain mitochondrial oxidative system, antioxidant blood activity, and the rat behavior in hypoxia] Eksp Klin Farmakol. 2003 Nov-Dec;66(6):16-9. Russian. PMID: 14743704 [PubMed - indexed for MEDLINE]

157: What's L-A-C got to do with it? Notes Undergr. 1997 Nov;(No 36):6. PMID: 11365206 [PubMed - indexed for MEDLINE]

158: James JS. Drug-related neuropathy: low acetylcarnitine levels found. AIDS Treat News. 1997 Feb 21;(No 265):6-7. PMID: 11364244 [PubMed - indexed for MEDLINE]

159: Ames BN. Delaying the mitochondrial decay of aging-a metabolic tune-up. Alzheimer Dis Assoc Disord. 2003 Apr-Jun;17 Suppl 2:S54-7. Review. No abstract available. PMID: 12813210 [PubMed - indexed for MEDLINE]

160: Barrett AM. A 1-year controlled trial of acetyl-L-carnitine in early-onset AD. Neurology. 2001 Feb 13;56(3):425. No abstract available. PMID: 11171924 [PubMed - indexed for MEDLINE]

161: Pepeu G. The phosphatidylserine story. Nutrition. 1999 Oct;15(10):789. No abstract available. PMID: 10501294 [PubMed - indexed for MEDLINE]

162: SLOTTA KH. MITOCHONDRIAL PHOSPHOLIPIDS IN RATS OF VARIOUS AGES. J Gerontol. 1963 Oct;18:326-9. No abstract available. PMID: 14071809 [PubMed - indexed for MEDLINE]

163: Beckman, Kenneth B., Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547-581, 1998.

164: Bonnefoy M, Drai J, Kostka T. [Antioxidants to slow aging, facts and perspectives] Presse Med. 2002 Jul 27;31(25):1174-84. Review. French. PMID: 12192730 [PubMed - indexed for MEDLINE]

165: Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006 Mar 10;160(1):1-40. Epub 2006 Jan 23. Review. PMID: 16430879 [PubMed - indexed for MEDLINE]

166: Diplock AT, Charleux JL, Crozier-Willi G, Kok FJ, Rice-Evans C, Roberfroid M, Stahl W, Vina-Ribes J. Functional food science and defence against reactive oxidative species. Br J Nutr. 1998 Aug;80 Suppl 1:S77-112. Review. PMID: 9849355 [PubMed - indexed for MEDLINE]

167: Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann N Y Acad Sci. 1992 Sep 30;669:7-20. Review. PMID: 1444060 [PubMed - indexed for MEDLINE]

168: Ward J. Free radicals, antioxidants and preventive geriatrics. Aust Fam Physician. 1994 Jul;23(7):1297-301, 1305. Review. PMID: 8060275 [PubMed - indexed for MEDLINE]

169: Davies KJ. Oxidative stress: the paradox of aerobic life. Biochem Soc Symp. 1995;61:1-31. Review. PMID: 8660387 [PubMed - indexed for MEDLINE]

170: Meydani M. Nutrition interventions in aging and age-associated disease. Ann N Y Acad Sci. 2001 Apr;928:226-35. Review. PMID: 11795514 [PubMed - indexed for MEDLINE]

171: Hayflick L. Biological Aging Is No Longer an Unsolved Problem. Ann N Y Acad Sci. 2007 Apr;1100:1-13. PMID: 17460161 [PubMed - as supplied by publisher]

172: Grant WB. Milk and other dietary influences on coronary heart disease. Altern Med Rev. 1998 Aug;3(4):281-94.PMID: 9727089 [PubMed - indexed for MEDLINE]

173: Esselstyn CB Jr. Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition. Prev Cardiol. 2001 Autumn;4(4):171-177. PMID: 11832674 [PubMed - as supplied by publisher]

Knowledge Search