By Benjamin V. Treadwell, Ph.D.
Should we exercise? Some would say “no.” Here’s their theory: the body – bones, muscles, organs – is built to withstand a predetermined number of hours of wear and tear. Once this limit is reached, part by part, the body fails. By speeding up the timetable with the stresses of exercise, we contribute to a shorter lifespan. True, there are variations in human lifespans but, according to this theory, they are attributable to the effects of good genes, “super genes,” creating body parts that can withstand more abuse. These theorists put more emphasis on diet and essential multivitamins, rather than exercise or a combination thereof.
Although it may be appealing to think that it’s “healthier” not to expend energy and work up a sweat a few times a week, there is quite a bit of evidence to the contrary. Here’s just one example. Exercise, especially aerobic exercise, has been shown to have a significant positive effect on cardiovascular health: improving vascular tone and lipid profile (raises HDL), as well as reducing the work (beats per minute) the heart has to perform (a strong-healthy heart has a lower resting heart rate).
Aside from the fact that it’s an excellent means of healthy weight control, recent research has also demonstrated that moderate exercise (running, walking) can actually improve the health of cartilage tissue. Could this help reduce/prevent the aches and pains associated with aging joints?
The Cartilage Connection
Adequate cartilage tissue at the ends of our bones allows for smooth, low friction, pain-free movement of our limbs. Moderate exercise seems to stimulate cartilage growth, improving the cushion of cartilage at the points of articulation. (Exercise also improves muscle tone and strength to keep our joints aligned, preventing damage.)
However, exercise that produces repetitive pounding of the joint surfaces, especially with excess weight, seems to have the opposite result: damage to the cartilage. This kind of chronic stress may lead to the development of one of the most common diseases of modern western civilization, osteoarthritis (OA). Although the incidence of this disease appears to be increasing (perhaps due, in part, to an increasingly obese population), our knowledge of it was limited…until recently.
Numerous investigators have reported markers of inflammation (IL-6, IL-1, TNF alpha) in the cartilage tissues of patients with OA. However, the biochemical mechanism(s) involved in the destruction of cartilage during the disease’s initiation and progression has not been clear.
A recent study revealed not only a number of intricate biochemical events leading to the destruction of cartilage, but also the probable cause of the pain associated with OA. The study, using a model system of OA, placed human chondrocytes (cartilage cells) in a specialized chamber to mimic the high shear stress conditions that lead to OA.
In response to the stress, a fatty acid-like inflammatory substance, (PGE2) was produced, as well as specific receptors to which it binds. This PGE2-receptor binding event triggered a series of specific chemicals and enzymes, which activated the master regulator of inflammation, NF-kB. The NF-kB (a transcriptional factor controlling gene expression) travels to the nucleus of the cartilage cell and turns on genes, carrying the code for several inflammatory agents, including cytokine IL-6.
The cytokine IL-6 is believed to be responsible for the pain associated with OA. And the series of reactions, initiated by stress on cartilage, appear to produce destructive machines, proteases, capable of tearing apart the constituents of cartilage.
PGE2 Receptors Revisited
Previous work also showed that large amounts of PGE2 were present in cartilage from patients with OA, identifying it as the principal substance that led to the disease. In fact, this hypothesis was popular about 30 years ago, when some orthopedists were prescribing aspirin for OA patients. They believed this inhibitor of the enzyme responsible for PGE2 production (cyclo-oxygenase or COX-2) would not only relieve the pain, but also help cure the disease.
The more recent study demonstrates, however, that stress on cartilage not only increases the levels of PGE2, but also affects the levels of two important receptors for it, namely EP2 and EP3. The former, EP2 (increases with stress), activates the pathway leading to cartilage destruction. The latter, EP3 (decreases with stress), inhibits this pathway. In other words, the destructive process is not the result of more PGE2 alone, but also more EP2 and less EP3.
Cartilage destruction is prominent in osteoarthritis. OA is commonly associated with obesity, misaligned joints, excessive trauma to joints (sports injury), and too much repetitive activity. All of these cause significant stress to the cartilage, the chondrocytes, which respond by attempting to “remodel” the cartilage to make it stronger. Unfortunately, cartilage synthesis seems to be inhibited.
How can we avoid the stress that starts the destructive chain reaction and promote cartilage growth? The answer for both brings us back to the value of moderate exercise, like walking (also running as long as it is of moderate intensity and your joints are healthy). It’s a great form of healthy weight control and is probably the most important method of prevention. It strengthens the muscles, ligaments and tendons that help keep the joints properly aligned. And it stimulates cartilage growth.
Are there other ways to improve cartilage health? Reported clinical studies have shown limited improvement in some OA patients taking the supplement chondroitin sulfate/glucosamine. Other natural sources currently being examined as potential OA therapeutics include plant-derived compounds such as curcumin (turmeric flavonol), a number of polyphenols like pynogenol and resveratrol, and the omega 3 fatty acids EPA/DHA.
Thanks to research like the study described earlier, a better understanding of the events leading to cartilage destruction and OA may lead to the development of new treatments for this painful and debilitating disease.
Osteoarthritis (OA) affects cartilage, the resilient material that covers the ends of bones and is necessary for near frictionless flexion and extension. The end result of the disease is a joint surface eroded to underlying bone. The affected joint has a high coefficient of friction, making movement without excruciating pain difficult. OA is commonly associated with excessive stress placed on the cartilage, either by blunt trauma (sports injury), or excessive stress due to repetitive pounding (such as excessive running), or obesity.
With the goal of providing information that could lead to new therapeutics for OA, a group of investigators set out to determine how one of the inflammatory agents associated with the disease, the cytokine IL-6, is activated during its early stages. The team, from Johns Hopkins University and the George Washington University Medical Center, published “Shear-induced interleukin-6 synthesis in chondrocytes: the roles of E prostanoid (EP)2 and EP3 in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-kB activation,” in the Journal of Biological Chemistry.
The article describes the investigators’ discovery of a complicated biochemical pathway. With an OA model system, designed to mimic the effects of stress on cartilage that would normally initiate the disease in humans, the researchers examined the expression of several genes in cartilage cells, chondrocytes, compared to chondrocytes under non-stress conditions.
The results showed a remarkable increase in several substances previously demonstrated to be up-regulated in OA cartilage. More importantly, the experiments revealed a sequence of events in the stressed chondrocyte, starting with an increased synthesis of the enzyme COX2 (cyclo-oxygenase 2), which in turn is responsible for the production of the inflammatory fatty acid substance, PGE2.
Coincident with the synthesis of PGE2 was increased synthesis of its receptor, EP2. The binding of PGE2 to EP2 initiated production of the signaling molecule, cAMP, which in turn, activated a cascade of enzymes, culminating in the activation of the master regulator of inflammation, NF-kB.
NF-kB, transported to the nucleus of the cell, activated specific inflammatory genes, including IL-6, as well as additional inflammatory cytokines. These activated specific cartilage proteases, producing destruction of cartilage and the characteristic OA condition (pain and immobile joints).
The researchers speculate that their data on this biochemical pathway may lead to therapeutics for early intervention in cartilage erosion, allowing OA to be more easily controlled.
Read abstract here.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.
Dr.Treadwell answers your questions.
question:I am a long-time customer and am extremely pleased with the Juvenon products. In a discussion with a friend the other day, he said he was contemplating taking human growth hormone. Can you give me any info about the use of human growth hormone? – D
answer:Although the claims for human growth hormone (HGH) may seem enticing, I don’t recommend taking it, except for a specific disorder and under a qualified health professional’s supervision. Why? It’s expensive and, apart from some human studies that showed increased lean body mass, most of the evidence for the benefits of HGH is anecdotal. On the other hand, negative side effects, including cancer cell growth, have been documented in animal studies. In my opinion, it’s not worth the gamble.
Benjamin V. Treadwell, Ph.D.,is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.