Life Extension Magazine February 2006
Antioxidants, Mitochondrial Damage, and Human Aging
By Edward R. Rosick, DO, MPH, MS
By Edward R. Rosick, DO, MPH, MS
Protecting the Mitochondria
Even mainstream scientific publications now recognize the importance of mitochondrial function in aging and disease. A study in the Annals of the New York Academy of Sciences highlighted how mitochondrial dysfunction caused by free radical-induced oxidative damage is a common marker in both aging and age-related diseases such as cancer. The authors note that cancer is associated with aging, and that adults aged 65 or older account for 60% of all cancers and 70% of all cancer deaths. According to the authors, not only it is likely “that increased susceptibility of mitochondrial DNA to oxidative damage and limited DNA repair capacity of the proteins involved in mitochondrial repair play a significant role in mutagenesis of aging,” but “mitochondrial dysfunction that accompanies aging may exert a major influence on carcinogenesis.”12
Fortunately, ample evidence suggests that diets rich in fruits and vegetables—and thus high in antioxidants—have significant protective effects against many age-related diseases. In addition, preliminary evidence indicates antioxidants exert direct protective effects against mitochondrial damage caused by free radicals. In another article in the Annals of the New York Academy of Sciences, the authors reviewed how certain antioxidants such as coenzyme Q10, N-acetylcysteine, and lipoic acid may neutralize the excess production of free radicals inside the mitochondria.13
Benefits of Lipoic Acid, Acetyl-L-Carnitine
Lipoic acid is considered an important antioxidant and crucial for a variety of mitochondrial reactions. In Europe, doctors prescribe lipoic acid to treat liver diseases and polyneuropathies. Recent research has shown that lipoic acid may be a useful adjunct in the fight against pathological and age-related changes seen in the brain.
One study examined how lipoic acid modulates neurotransmitters in the brains of aged rats. The older rats given lipoic acid supplements increased their levels of several important neurotransmitters, including dopamine, serotonin, and norepinephrine. Postulating that this increase could be due to lipoic acid’s antioxidant action, the authors concluded, “supplementation of lipoic acid could represent a viable therapeutic approach to diminish oxidative stress in the central nervous system and thereby modulate the levels of neurotransmitters during [aging].”14
Another study, coauthored by Dr. Ames, found that in aged rats, lipoic acid and acetyl-L-carnitine significantly protected mitochondria from oxidative damage and age-associated decay. According to the authors, “feeding old rats acetyl-L-carnitine plus lipoic acid restores mitochondrial function, lowers oxidants . . . improves the age-associated decline in ambulatory activity and memory . . . and prevents mitochondria from oxidative decay and dysfunction.”15
Antioxidants That Combat Alzheimer’s
In addition to lipoic acid, other antioxidants can help protect the brain against the ravages of aging. Beta-carotene and vitamins C and E show great promise in the fight against Alzheimer’s disease. Alzheimer’s, the most common cause of dementia in adults aged 65 and older, affects more than 15 million people worldwide. One major change that occurs in the brains of Alzheimer’s sufferers is generalized oxidative damage to neurons. However, current prescription medications for Alzheimer’s focus only on increasing levels of the neurochemical acetylcholine, not on combating oxidative damage to neurons. Multiple studies support the idea that antioxidants have a place as a front-line therapy against Alzheimer’s.
One such study of 442 elderly Swiss patients directly correlated higher blood levels of two common antioxidants (beta-carotene and vitamin C) with better memory.16
A study published in the Archives of Neurology in 2004 examined Alzheimer’s risk in people who took antioxidant supplements. The study found that “use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD [Alzheimer’s disease]. Antioxidant supplements merit further study as agents in the primary prevention of AD.”17
Vitamin E May Prevent Muscle Loss
As people age, not only do their bones become brittle, but their muscle tissues shrink and atrophy, a condition known as sarcopenia. It has been estimated that between the ages of 20 and 80, skeletal muscle mass decreases by 35-40% in men and women. While brittle bones secondary to osteoporosis certainly contribute to the greater incidence of hip fractures and other debilitating injuries in the elderly, leg weakness caused by sarcopenia is a major contributing factor to the falls that cause hip fractures. When sarcopenia robs people of their ability to walk, climb stairs, or perform the simple task of getting in and out of a chair, it confines them to an unhealthy, sedentary lifestyle.
While studies are ongoing, some researchers believe that intramuscular mitochondrial DNA damage caused by free radicals may be a significant factor in the loss of muscle mass seen in the aged.6 The use of antioxidants—specifically, vitamin E—may help prevent sarcopenia in the elderly. A report from Johns Hopkins examined the relationship between plasma levels of antioxidants and muscle strength in women aged 70-79. Higher carotenoid and alpha tocopherol (vitamin E) levels were independently associated with greater muscle strength,18 leading the authors to conclude that sarcopenia in older adults may result in part from oxidative stress, and that antioxidants may be protective.
Lutein, Zeaxanthin Protect Vision
Many longitudinal studies show that high intake of carotenoids—the phytocompounds responsible for the red to yellow pigmentation in fruits and vegetables—can protect against various age-related disease states, including vision loss. Two of the most useful carotenoids for combating age-related vision loss caused by cataracts are lutein and zeaxanthin.
These potent antioxidants are thought to help prevent cataracts by protecting the eye lens from the damaging effects of ultraviolet radiation and endogenous free radical formation. Three recent studies have demonstrated that people with a high intake of lutein and zeaxanthin have significantly lower risks of developing cataracts compared to those with a low intake.19-21 In addition, research has shown that even in people who have already developed cataracts, lutein supplementation can help improve vision.22
Age-management medicine is about more than just extending the years of life. Its goal is to lengthen and optimize the years of healthy, functional living by preventing the diseases that commonly afflict older adults. With a little common sense and healthy everyday behaviors—including regular exercise, a diet rich in fruit, vegetables, and lean protein, and use of antioxidant supplements—you can ensure that you have both the chance and the capacity to enjoy a long, healthy life.
1. Harman, D. Aging: a theory based on free radical and radiation chemistry. The University of California Radiation Laboratory Report, No. 3078. 1955 Jul 15; Univ. of California, Berkley, CA.
2. Harman D. The aging process. Proc Natl Acad Sci USA. 1981 Nov;78(11):7124-8.
3. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993 Sep 1;90(17):7915-22.
4. Barja G. Free radicals and aging. Trends Neurosci. 2004 Oct;27(10):595-600.
5. Junqueira VB, Barros SB, Chan SS, et al. Aging and oxidative stress. Mol Aspects Med. 2004 Feb;25(1-2):5-16.
6. Ashok BT, Ali R. The aging paradox: free radical theory of aging. Exp Gerontol. 1999 Jun;34(3):293-303.
7. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann NY Acad Sci. 1998 Nov 20;854:155-70.
8. Mandavilli BS, Santos JH, Van Houten B. Mitochondrial DNA repair and aging. Mutat Res. 2002 Nov 30;509(1-2):127-51.
9. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000 Aug;29(3-4):222-30.
10. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood.). 2002 Oct;227(9):671-82.
11. Mecocci P, Polidori MC, Troiano L, et al. Plasma antioxidants and longevity: a study on healthy centenarians. Free Radic Biol Med. 2000 Apr 15;28(8):1243-8.
12. Singh KK. Mitochondrial dysfunction is a common phenotype in aging and cancer. Ann NY Acad Sci. 2004 Jun;1019:260-4.
13. Miquel J. Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann NY Acad Sci. 2002 Apr;959:508-16.
14. Arivazhagan P, Panneerselvam C. Neurochemical changes related to ageing in the rat brain and the effect of DL-alpha-lipoic acid. Exp Gerontol. 2002 Dec;37(12):1489-94.
15. Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann NY Acad Sci. 2002 Apr;959:133-66.
16. Perrig WJ, Perrig P, Stahelin HB. The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc. 1997 Jun;45(6):718-24.
17. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8.
18. Semba RD, Blaum C, Guralnik JM, et al. Carotenoid and vitamin E status are
associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res. 2003 Dec;15(6):482-7.
19. Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Greger JL. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol. 1999 May 1;149(9):801-9.
20. Brown L, Rimm EB, Seddon JM, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr. 1999 Oct;70(4):517-24.
21. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr. 1999 Oct;70(4):509-16.
22. Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study. Nutrition. 2003 Jan;19(1):21-4.