Juvenon Health Journal volume 3 number 12 december 2004
To answer the age-old question of how long humans can live, scientists for decades have investigated the processes by which cells divide, senesce and die. In the 1960’s it was shown that cells grown in culture proliferate rapidly, then slow down and die after a limited number of replications. In the last decade, the mechanisms associated with apoptosis and other cell death phenomena have been elucidated. More recently, scientists have turned their attention to senescence induced by stress, which has major implications for healthy aging. For an overview of stress-induced senescence, visitThe Journal of Clinical Investigation.
(For the full article in PDF format, click here.)
“When cells get stressed: an integrative view of cellular senescence”
J. Clin. Invest. 113:8-13 (2004).
By Benjamin V. Treadwell, Ph.D.
Why do we age? The formula in today’s title indicates that the time we spend on earth is inversely proportional to the stress our bodies encounter. But what do we mean by cellular stress, and why does it cause us to age and eventually die?
THE CELLULAR AGING PROCESS
In 1961 Leonard Hayflick, a scientist now at the University of California, San Francisco, made an interesting observation on the age-old question of why man lives a fixed amount of time. Hayflick and his colleague, Moorhead, demonstrated that cells from an embryo, when placed in culture, grew and thrived. However, the rate of growth diminished as the cells continued to reproduce by cell division. Eventually the cells ceased to divide and died. This cycle of growth by cell division, and eventual death, was remarkably reproducible. In fact, Hayflick could predict exactly when a cell would die – normally after it divided 40-50 times. This morphed into the Hayflick theory (or limit) of aging, and later to replicative senescence, which posits that each of us is born with a predetermined life span based on the number of times our cells divide before dying.
Two decades after this seminal work, another important discovery was made, which the Hayflick supporters believed proved this theory. Our genetic blueprint, DNA, is coated with specialized protective proteins, histones, that form the 23 pairs of chromosomes containing all of our genetic information. The ends of each of the chromosomes contain a unique structure now known as a telomere. It, too, consists of a specific type of DNA in combination with specialized proteins. This structure is required for normal cell replication (division). If it is lost or defective, the cell cannot divide and consequently becomes what is labeled a replicative senescent cell. The majority of our cells initially contain telomeres of a certain length, and with each cell division this length is diminished by a fixed amount. It is now known that the cell can no longer reproduce itself once the telomeres wear down to some minimum length. So it appeared that Hayflick, with his depressing discovery that our time on earth is predetermined, might be right. Or not! There is more than enough room for the optimist to argue that this is not necessarily a definitive hypothesis. In fact, as you will see, it is full of holes. Life can be extended!
The telomeres, it turns out, can be lengthened by the action of a specialized enzyme, telomerase. Since this enzyme can rejuvenate the telomere to its youthful length, why don’t our cells continue to divide? Although virtually all of our cells contain this life-saving enzyme (or the potential to produce it), it remains in a relatively inactive form once the constituent cells of an organ have reached maturity. In other words, many of our cells don’t need this telomere-extending enzyme because they don’t divide after they reach maturity.
The telomere-shortening mechanism of aging is known as replicative senescence. That is, the cell senesces, or ages, as it reaches its reproductive limit. However, there is another form of senescence, induced by stress, that in fact may be more important than replicative senescence in our bodies (as opposed to in the artificial conditions of cell culture). In fact, this form of senescence may reflect the real world, rather than the results Hayflick first demonstrated in the artificial environment of cell culture.
Evidence is mounting to support the hypothesis that stress, in the form of toxic oxidants, as well as other DNA-damaging agents produced by our cells and the environment (radiation, smoke, toxic metals), can induce cellular senescence. Furthermore, cellular aging can result from over-production of certain regulators (oncogenes) of cell division. These oncogenes, too, can be activated by cell stress-inducing toxic agents. These forms of stress do not involve telomere shortening, yet can cause a cell to senesce in a relatively short period of time.
We all know how age affects us; we are slower, both mentally and physically, with less energy. This process continues in a downward spiral until death. Once a certain amount of damage occurs to the cell, particularly the DNA comprising our genetic code, a cellular mechanism is activated to rid the body of the cell. The cell responds to toxic oxidant-induced cell damage by producing specialized proteins. These proteins turn on a pathway to digest the cell and remove it from the body. Interestingly, these proteins also serve a critical role in the body. Those very cells that have damaged DNA may contain a cancer-producing mutation. So by eliminating these cells, the body may be protecting itself against cancer. In other words, there is a trade-off. Our body may be able to avoid cancerous growth by eliminating senescent cells, but this also may contribute to the aging process.
Scientists recently discovered that some of the cellular-derived agents that trigger the senescent cell-death pathway increase in tissues with age. In other words, these substances that are produced as a cell progresses toward senescence may represent an accurate marker of the biological age of a tissue. We all know our chronological age, but the more accurate determination of age is one that reflects the health of our tissues.
Knowing the level of these markers can be of enormous value in determining the effectiveness of a dietary supplement or drug in inhibiting those events that age a cell. For example, caloric restriction, the only proven method to extend life from flies to mammals, remarkably lowers levels of these age markers. On the flip side, expose cells to high levels of the known aging effects of oxidant stress, and these markers go up prior to the cell becoming senescent, and being eliminated from our tissues. Thus, these markers appear to be excellent indicators of cellular health.
The messages emerging from the majority of aging studies are still not entirely clear. However, most of the studies do implicate toxic oxidants (free radicals produced during cellular metabolism) and environmental agents (toxic chemicals, radiation, UV light) as important factors involved in accelerating the aging process. That is, factors that place stress on the cell appear to be directly involved in the activation of biochemical pathways leading to cellular senescence and ultimately death.
The option for us is to take measures to try to minimize the cell-damaging effects of these toxic agents through a healthy lifestyle, proper nutrition, and exercise. Adding vitamins as well as additional micronutrients to our daily regimen may also be of help in neutralizing the toxic substances before they attack and damage the cell.
I have a question about the product HGH and Juvenon. What’s the difference? Should I try to take Juvenon or HGH? I am a 41 year old female and I noticed age creeping in.
C.B.,via emailBenjamin V. Treadwell, Ph.D. is a member of Juvenon’s Scientific Advisory Board and formerly an associate professor at Harvard Medical School.
Send your questions to AskBen@juvenon.com.
Answers to other questions are available athttp://juvenon.com/product/qa.htm.
Juvenon™ Cellular Health Supplement does not contain hormones. It contains compounds our bodies normally make, but as we age the quantity being synthesized by our cells decreases. This is the logic behind supplementing with the Juvenon tablets to help maintain normal healthy levels of these important nutrients. They help support cellular health and increase the production of energy by the mitochondria in the cell. HGH (human growth hormone) must be taken under a doctor’s supervision. There are potential dangers associated with taking this hormone, as it has an effect on numerous metabolic pathways including potential stimulation of unwanted cellular growth. Please consult your physician with any question regarding HGH.