By Michelle Cotroneo, Ph.D., Scientific Advisor

Type 2 diabetes is a disorder of inadequate production of, or resistance to insulin, a hormone produced by the pancreas. A key function of insulin is to move glucose from the blood into the cells, where it is used as energy.  Without sufficient insulin function, glucose accumulates in the blood, leading to complications.  Some of the disorders that can occur as a result of type 2 diabetes include: hypertension, blindness, stroke, nephropathy (kidney disease), neuropathy (nerve damage), and skin infections.

It is estimated that there are 17.9 million diagnosed cases of diabetes in the United States and 57 million people with pre-diabetes. Risk for diabetes is increased in those with a family history of the disease, in certain ethnic groups, and in overweight or obese individuals. Aging also increases the risk for developing diabetes, affecting 23.1% of Americans over 60 (statistics from the National Diabetes Fact Sheet, American Diabetes Association). It is also estimated that by 2025, two thirds of diabetic individuals worldwide will be age 60 or older (1).

Why is aging associated with increased diabetes risk?

It is thought that the increased chance of developing type 2 diabetes as a person ages is related to increasing insulin resistance. In an interesting study comparing insulin sensitivity between different groups of individuals (2), no difference was identified in insulin sensitivity between old and young athletes, between older and younger normal weight individuals, or between older and younger obese subjects. The athletes demonstrated the highest insulin sensitivity, followed by the normal weight individuals, with obese subjects having the lowest sensitivity to insulin.  The authors concluded that aging alone cannot account for insulin resistance, but that the decreased physical activity and obesity that can occur with aging can be responsible for age-related insulin insensitivity.

An increasing amount of research has been devoted to studying the relationship between physical activity, obesity and diabetes. It is now generally accepted that the presence of abdominal fat increases the risk for diabetes and cardiovascular disease. Although abdominal fat increases during aging, it may not result in a noticeable increase in weight, as fat distribution also changes as a consequence of aging. Fat deposition in the arms, legs and hips decreases, while it increases in the abdominal area. Subcutaneous fat is under the skin, and is not associated directly with increased disease risk. On the other hand, visceral fat located deeper in the body collecting around the organs is associated with the risk for diabetes and cardiovascular disease.

How can fat increase diabetes risk?

Adipose (fat) tissue is a complex endocrine organ that produces hormones and adipocytokines that are involved in the regulation of glucose and fat metabolism. Expansion of this tissue is accompanied by the infiltration of macrophages (inflammatory cells). Abdominal obesity can result in adipocyte dysfunction, resulting in altered production of hormones and adipocytokines.  Perturbations in the balance of these factors and the presence of macrophages results in altered insulin sensitivity, glucose utilization, pancreatic cell function, fat deposition and inflammation (3,4).

Can you get rid of visceral fat?

It is a well known fact that risk for diabetes in overweight or obese individuals can be decreased by exercise and weight loss. But do these measures result in a decrease in visceral fat? A comprehensive review of scientific studies in this area has shed important light on these questions (5). These authors concluded that moderate weight loss resulted in preferential loss of visceral fat over subcutaneous fat, but that greater weight loss reduced this effect. They also found that there was no evidence that any type of weight loss strategy was more effective than another in preferentially reducing visceral adipose tissue.  Taken together, the current research underscores the importance of maintaining a healthy weight and continuing to exercise as we age.

1. King H, Aubert RE, Herman WH. Diabetes Care 1998; 21(9): 1414-31.

2. Amati F, Dubé JJ, Coen PM, Stefanovic-Racic M, Frederico G. Diabetes Care 2009; 32(8): 1547-9.

3. Ioannidis, I. Angiology 2008; 59 (39S): 39-43.

4. Hajer GR, van Haeften TW, Visseren FLJ. European Heart Journal 2008; 29: 2959–71.

5. Chaston TB, Dixon JB. International Journal of Obesity 2008; 32: 619–28.

Posted under: Diabetes.

Tags: aging, type 2 diabetes, visceral fat

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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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