Research in science shows that glutathione, a major cellular synthesized antioxidant, is at the heart of aging and could slow the process.
Knowledge about the biological basis of aging is limited and many theories reflect the current direction of what is “hot” in research. Of these, shortening of “telomeres” and the “theory of free radicals” draw special attention at the present moment (1). To this end, recent set of data places glutathione (GSH) in the heart of these two theories with a potential role in slowing the progression of aging.
Glutathione and free radical theory
The theory that links aging to oxidative stress and free radicals was first proposed by Dr. Harman in 1956 (2). It stated that the age and loss of physiological functions were due to progressive accumulation of oxidative damages.
Currently, this theory of aging involves the overproduction of free radicals and subsequent damage to cellular structures, macromolecules, and in particular mitochondrial DNA (mtDNA). Consequently, the mutation accumulation in mtDNA leads to the production of defective mitochondria, irreversible oxidative damages and cell death. The latter affects the immediate environment of the organ and this oxidative vicious cycle has been proposed to be a relevant factor in the mammal’s longevity (3).
Consistent with this theory, studies in mice show that during tissues and mitochondria aging, the ratio of “non-oxidized glutathione/oxidized glutathione” gradually moves towards oxidation (rust) (4, 5). Moreover, in another mouse model that has a life shortened by 48% compared to control mice, the researchers noticed a significant decrease in mitochondrial GSH levels in the brain, skeletal muscles and liver (5). Finally, another study points to a direct relationship between the amount of mtDNA damages and the amount of oxidized glutathione in the mitochondria (6), suggesting that beyond no doubt glutathione protects mitochondria.
In another study published in 2004, an American research team has systematically assessed the effect of aging on glutathione, in different rat organs. They found that GSH level decreases in all tissues, with aging (7).
Another eloquent proof on the GSH role in slowing the aging process was published in 1989, when mice that were fed with whey proteins, a natural precursor of glutathione synthesis, extend their longevity by five months (8, 9)
In light of these results, GSH protects mitochondria and slow aging, in the context of this theory (10).
A telomere is the region at the end of a linear chromosome. In humans, telomeres shrink each time a cell divides (with the exception of germ cells that possess active telomerase), because of the inability of the cellular machinery to “duplicate” the last elements of this DNA structure. This loss of genetic information is at the heart of an exciting scientific debate and would be responsible for several types of diseases, including aging (11).
To this end, numerous studies show that short telomeres are characteristic of various human diseases associated with aging such as heart disease, ulcerative colitis (bowel), liver cirrhosis, atherosclerosis, and several premature aging syndromes (12).
Recently (2011), a study carried out by a Singapore research team, made the discovery that when telomerase is present in large quantities in cells, it also plays a major role in neutralizing and blocking the cellular production of free radicals (13). These beneficial effects are mediated directly by the increase in cellular non-oxidized glutathione level.
Conversely, the loss of telomerase leads to a sharp increase in free radicals creation due to oxidative stress (13).
Recent published scientific studies are bringing together two major theories of aging. Glutathione, a naturally synthesized antioxidant that helps to keep the cell in a non-oxidative state, is at the heart of these theories. As it is possible to raise systemic GSH levels naturally, via glutathione precursors rich nutrition (eg. undenaturated whey proteins (15)), and not telomerase’s level, scientific studies suggest that it is possible to counter the regressive effects of aging by maintaining a high amount of non-oxidized glutathione (1, 14).
1. Mari M, Morales A, Colell A, Garcia-Ruiz C, Fernandez-Checa JC. 2009. Antioxid Redox Signal 11: 2685-700
2. Harman D. 1956. J Gerontol 11: 298-300
3. Jang YC, Remmen VH. 2009. Exp Gerontol 44: 256-60
4. Rebrin I, Kamzalov S, Sohal RS. 2003. Free Radic Biol Med 35: 626-35
5. Rebrin I, Sohal RS. 2004. Exp Gerontol 39: 1513-9
6. de la Asuncion JG, Millan A, Pla R, Bruseghini L, Esteras A, et al. 1996. FASEB J 10: 333-8
7. Liu H, Wang H, Shenvi S, Hagen TM, Liu RM. 2004. Ann N Y Acad Sci 1019: 346-9
8. Bounous G, Batist G, Gold P. 1989. Clin Invest Med 12: 154-61
9. Bounous G, Gervais F, Amer V, Batist G, Gold P. 1989. Clin Invest Med 12: 343-9
10. Green RM, Graham M, O’Donovan MR, Chipman JK, Hodges NJ. 2006. Mutagenesis 21: 383-90
11. Blasco MA. 2005. Nat Rev Genet 6: 611-22
12. Monaghan P. Ann N Y Acad Sci 1206: 130-42
13. Indran IR, Hande MP, Pervaiz S. Cancer Res 71: 266-76