By Michelle S. Cotroneo, Ph.D., Scientific Advisor

Approximately 1 out of every 6 men will be diagnosed with prostate cancer. Prostate cancer is the most common non-cutaneous malignancy and is second only to lung cancer in deaths due to cancer in American men. Prostate cancer is a disease of aging, with a median age of 79 years (1). Latent prostate cancer, which causes no clinical manifestations, is often found at autopsy by microscopic examination of prostatic tissue. Analysis of autopsy data showed that 15 to 30% of men over the age of 50 had latent prostate cancer, with the incidence increasing to 60-70% by the age of 80 (2,3). In a society where life expectancy has increased, it is important to determine how aging is related to prostate cancer risk.

An important research approach begins at the cellular level. Such studies characterize the interaction between cancerous cells and those that surround them. Senescent cells are those that have lost the ability to divide, and are considered to be “aged”. It is hypothesized that senescent cells may create a permissive or growth-stimulatory environment for cancerous cells. Experimental data have shown that cells immediately surrounding a prostate carcinoma (stromal cells) can cause tumor progression (4). Cellular interactions are mediated by various proteins, including growth factors and enzymes.

In addition to studying interaction between cells, characterizing the relationship between aging and disease often involves examining signaling pathways that occur within cells. One signaling pathway with an important role in both aging and prostate cancer is mediated by the cellular enzyme, mTOR (mammalian target of rapamycin), which functions in cellular growth and metabolism. mTOR signaling is frequently increased in prostate and other cancers. Experimental evidence shows that inhibition of this pathway in living organisms prolongs lifespan, a result that is also achieved with calorie restriction (5); therefore, this pathway may play a central role in age-related cancer.

Other theories about how advancing age is a risk factor for certain diseases focus on the role of accumulating damage to DNA. Recent advances in technology are helping researchers conduct large scale genetic association studies to determine gene-disease relationships. Investigators test human DNA samples for the presence of aberrant chromosomal regions, genes, or single nucleotides. Statistical testing is used to determine if a particular variant occurs with higher frequency in samples derived from diseased individuals, compared to those from persons not having the disease. Interestingly, a review of the recent data from such studies has revealed that there are several prostate cancer variants which serve functions in aging-related cellular pathways (6).

Despite the varying approaches of researchers studying age-related diseases, they share a common goal: to develop strategies to treat or prevent disease.

References

1. Yancik R. Cancer J 2005; 11:437-441.

2. Pienta KJ, Esper PS. Ann Intern Med 1993; 118:793-803.

3. Franks LM, Durh MB. Lancet 1956; 17:1037-1039.

4. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Cancer Res 1999; 59:5002-5011.

5. Blagosklonny MV. Cancer Biology & Therapy 2008; 7:1520-1524.

6. Cluett C, Melzer D. Mechanisms of Ageing and Development 2009; 130: 553–563.

Posted under: Cancer, Cell Senescence.

Tags: aging, cellular senescence, prostate cancer

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By Michelle S. Cotroneo, Ph.D., Scientific Advisor

Coronary artery disease (CAD) is a narrowing or blockage of the arteries leading to the heart. It is the leading cause of mortality in the United States. This condition can reduce blood flow to the heart, which can lead to angina (pain). Complete blockage of the vessels can lead to death of heart muscle (heart attack).

CAD results from the formation of plaques in the lining of the arterial walls, a condition referred to as atherosclerosis. Plaques are composed of fat, cholesterol, cellular waste products, calcium, platelet clumps, and fibrin. Their accumulation over time leads to narrowing of the blood vessels and potential clot formation.

Factors known to increase risk of CAD include hypertension, diabetes, hypercholesterolemia, hyperlipidemia, smoking, sedentary lifestyle, high blood levels of the amino acid, homocysteine, and obesity. Other lifestyle factors, such as excess alcohol consumption, sleep apnea, and stress can also contribute to the development of CAD. Most of these factors can be managed or changed.

Non-modifiable risk factors are family history and age. The incidence of cardiovascular diseases, including CAD, increases with age. Men develop coronary artery disease at a younger age than women. However, the incidence for CAD in women increases following menopause, eventually becoming equal to that in men. This is thought to be due to the loss of the protective effects of estrogen on the arteries.

Why is age is a risk factor for cardiovascular disease?

Age-related changes in the arteries may play a role in the development of CAD. Arterial walls stiffen and thicken with age, losing their elasticity and ability for expansion to accommodate blood flow, resulting in hypertension. Understanding the cellular mechanisms behind vascular aging is the subject of a vast number of research studies.

Oxidative stress and inflammatory processes occurring in the endothelial cells have been hypothesized to contribute to CAD by promoting atherosclerosis. The formation of reactive oxygen species (ROS), such as peroxide, in aging endothelial cells activates the production of inflammatory cytokines and depletes nitric oxide (NO) levels. Nitric oxide has protective functions, including the prevention of platelet aggregation and control of inflammatory signaling pathways. The increase in inflammatory cytokines, coupled with a reduction in vasculoprotective NO can result in dysfunction or death of the endothelial cells.

Interestingly, comparative biologists have provided insight into the underlying cellular mechanisms of aging by comparing species with a short lifespan with those having longer ones. Existing comparisons support the theory that oxidative stress and production of ROS contribute to aging, and that vasculoprotection are predicted to occur with a reduced and/or delayed onset of production of ROS and increased defense mechanisms (Ungvari Z, et. al, Front Biosci. 2008, 13:5056-70). Ongoing and future biomedical research will continue to shed light on the relationship between vascular aging and coronary artery disease. Clinical research, such as the VALIDATE Study (ClinicalTrials.gov identifier: NCT00246493) will aid in understanding why age is such an important risk factor for the development of coronary artery disease.

Posted under: Cardiovascular diseases.

Tags: coronary artery disease, vascular aging

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By Ryan Acosta, Staff Writer

No dashing young Victorian era gentleman would venture out in the streets without his walking stick. It was one of the essential fashion apparels for men back then, a symbol of elegance and affluence. In contrast, today’s young men would probably scoff at the notion of roaming around with walking sticks.

That’s understandable enough if you consider the it’s-hip-to-be-young trend that’s being perpetually portrayed in the mass media. In the modern youth’s psyche, the walking stick is synonymous to old age, to frailty, and, perhaps, to arthritis. For the vast majority of those strolling the streets equipped with walking sticks these days are old people struggling with arthritis, particularly osteoarthritis.

Osteoarthritis is the most common form of arthritis and occurs in more than 27 million Americans (Helmick, C., Felson, D., Lawrence, R., Gabriel, S., et al, 2008). Because osteoarthritis usually affects the knee and hip, it is the main reason for disability in the US (Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, et al, 1994).

What makes this disease very painful is that it slowly chews the top portion of the cartilage, which is the soft that prevents bones from colliding. In time, the cartilage is entirely broken down and bones rub together. Constant collision between bones causes severe pain and swelling and gradually deforms the affected joint.

Symptoms

According to the Mayo Clinic, majority of patients with osteoarthritis complain of severe pain, especially when moving. Patients may also experience stiffness, tenderness, and a “grating sensation” in the affected joint. It is generally suggested that individuals should see a doctor if the aforementioned symptoms persist for two or more weeks.

Diagnosis

According to the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), there is not one test that can be performed to identify osteoarthritis. Usually, it is diagnosed by X-ray tests, which normally reveals bone and cartilage protrusions in affected joints. However, doctors would only recommend X-ray tests after physical examination of the patient showed joint swelling and tenderness, decreased motion of the joints, or visible damage to the joints. Aside from X-ray tests, synovial fluid analysis, blood tests, and other exams are also performed to diagnose osteoarthritis.

Aging and Osteoarthritis

Age is not the main risk factor for osteoarthritis. Joint injury, obesity, genetic defect in joint cartilage, severe stress on the joints resulting from occupational tasks, and other things may cause osteoarthritis (NIAMS). However, the prevalence of individuals affected with osteoarthritis increases with age. And many elderly people are not aware that they have osteoarthritis until X-ray tests are performed since common signs and symptoms (such as pain, stiffness, and tenderness in the joint area) do not necessarily occur at all times. In fact, it is estimated that about 70% of people above 65 may be diagnosed with osteoarthritis upon X-ray examination (Lane and Thompson, 1997).

As humans grow older, chondrocytes, the cells in the cartilage, are not replaced at a consistent rate. This results in an older chondrocyte population in the cartilage and makes it prone to degeneration (Bulkwalter and Mankin, 1998).

Treatment

Right now, there is no cure for osteoarthritis. Joint replacement surgery is sometimes performed if the pain is very severe and untreatable with normal pain medication. Treatment usually aims to alleviate the pain and other symptoms that cause disability to the patient. Analgesics, like acetaminophen, are the common medications for osteoarthritis (Brandt, 2000). Non-steroidal anti-inflammatory drugs (NSAID) are also used to treat osteoarthritis, which not only minimize pain but also reduces inflammation around the affected joints.

Research

Osteoarthritis is really a debilitating disease. As such, many studies are now being conducted in order to know more about it, particularly on determining its exact causes and developing better treatment. Tissue engineering therapy is perhaps the most promising research that is being conducted to treat osteoarthritis. Studies in this field focus on ways to develop techniques on transplanting healthy cartilage cells (preferably stem cells) to damaged joints.

The possibilities are really promising. The time will really come when people, especially elderly people, with osteoarthritis will not experience debilitating pain and disability.

References:

Brandt, K.D. The role of analgesics in the management of osteoarthritis pain. American Journal of Therapeutics. 7.2 (2000): 75-70.

Buckwalter , J.A. and Mankin, J.H. Articular Cartilage: Degeneration and Osteoarthritis, Repair, Regeneration, and Transplantation. Instructional Course Lectures. 47 (1998): 487-504.

Guccione, A.A., Felson D.T., Anderson J.J., Anthony J.M., Zhang Y., Wilson P.W., et al. The effects of specific medical conditions on functional limitations of elders in the Framingham Study. American Journal of Public Health. 84 (1994): 351-8.

Helmick, C., Felson, D., Lawrence, R., Gabriel, S., et al. Estimates of the Prevalence of Arthritis and Other Rheumatic conditions in the United States. Arthritis & Rheumatism 58.1 (2008): 15-25.

Lane, N.E. and Thompson, J.M. Management of osteoarthritis in the primary-care setting: an evidence-based approach to treatment. American Journal of Medicine 103.6 (1997): 25-30.

Mayo Clinic. Osteoarthritis: Symptoms. October 13, 2009. http://www.mayoclinic.com/health/osteoarthritis/ds00019/dsection=symptoms.

NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases). What Is Osteoarthritis? September 2006. http://www.niams.nih.gov/Health_info/Osteoarthritis/osteoarthritis_ff.asp.

Posted under: Osteoarthritis.

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