Vitamin E

Inclusion of vitamin E (DL-alpha-tocopherol) in the culture medium for human diploid cells greatly prolongs their in vitro lifespan. The addition of 100 mug of DL-alpha-tocopherol per ml of medium has allowed us to culture WI-38 cells for more than 100 population doublings to date. (These cells normally have an in vitro lifespan of 50 +/- 10 population doublings.) Cells at the 100th population doubling have a normal diploid karyotype, appear to behave in all other respects like young WI-38 cells, and are still actively dividing.

Previously we reported [Packer, L. & Smith, J.R. (1974) Proc. Natl. Acad. Sci. USA 71, 4763-4767] that the lifespan of WI-38 human diploid fibroblasts in vitro was significantly increased by continuously growing the cell cultures in the presence of vitamin E(dl-alpha-tocopherol), but in 19 subsequent subcultivation series we were unable to reproduce these findings. While vitamin E is incorporated into the cells and is able to act effectively as an antioxidant, apparantly is intracellular antioxidant properties alone do not routinely result in an increase of cell lifespan.

Vitamin E refers to a family of several compounds that possess a similar chemical structure comprising a chromanol ring with a 16-carbon side chain. The degree of saturation of the side chain, and positions and nature of methyl groups designate the compounds as tocopherols or tocotrienols. Vitamin E compounds have antioxidant properties due to a hydroxyl group on the chromanol ring. Recently, it has been suggested that vitamin E may also regulate signal transduction and gene expression.

Longevity can be explained by the free radical theory of aging, and caloric restriction (CR) studies showed that CR-induced lifespan extension is associated with the prevention of a decrease in oxidative stress. Non-enzymatic lipophilic antioxidants may play a pivotal role in our aging process, and are reflected in our dietary lifestyle and dietary supplementation. Their significance lies in their general good absorption and slow excretion within our body.

Cellular senescence is a tumor suppression mechanism. We previously reported that CKII downregulation induces senescence in human lung fibroblast IMR-90 and colon cancer HCT116 cells. In this study, potential longevity drugs, including rapamycin, vitamin C, and vitamin E, blocked CKII downregulation-mediated senescence through reduction of reactive oxygen species (ROS) production in HCT116 cells.

The statistical characteristics of body weight in a number of longitudinally studied mouse populations were examined. Frequency distribution of body weights appears to be rather "fluid" (though within a strict range), changing from symmetric to positively skewed to symmetric and finally to negatively skewed as the mice pass through the stages of early maturity, middle age, and senescence. Because body weight is a highly integrated physiological variable, it is postulated that various diets which affect survivorship would affect body weight frequency distribution similarly.

Antioxidants have been linked to protection against degenerative diseases associated with aging. Plasma concentrations were determined for and 7-d diet records collected from 200 women and 231 men aged 20-95 y who took part in the Baltimore Longitudinal Study of Aging. Men consumed more vitamin A from animal and less from vegetable sources than did women. These sex differences are reflected in plasma concentrations of retinol and beta-carotene.

Restriction of energy intake (ER), without malnutrition of essential nutrients, has repeatedly been demonstrated to increase longevity in rodents. In the antioxidant theory of aging the lack of balance between the generation of free radicals and free radical scavenging was thought to be a main causal agent, in the aging process. From this point of view the antiaging effect induced by ER might be due to the lower rate of free-radical production and related damage induced by a lower metabolic rate. The antiaging effects of ER might also occur in humans.

The hypothesis of the atherogenic role of oxidized. LDL lipoproteins and the observation of the longevity of individuals on a "mediterranean diet" led to the concept that antioxidant vitamins may exert cardiovascular protective effects. In this first article, we summarize the results of the main epidemiological studies which analyzed the influence of dietary intakes (or resulting plasma concentrations) in vitamin E (alpha-tocopherol), vitamin A (beta-carotene) or vitamin C (ascorbic acid).