By Michelle Cotroneo, Ph.D., Scientific Advisor

A cataract is a clouding of the lens, the structure that focuses light onto the retina.  The cloudiness is caused by aggregation of lens proteins, and results in a reduction in the amount of light that reaches the retina.  Cataract can result in vision changes such as blurriness, color distortion, sensitivity to glare, reduced night vision, or double vision.  Cataract is the principle cause of blindness worldwide (1).  If vision is severely impaired, the treatment for cataract is surgical removal of the lens, and in some cases, replacement with an implant. 

There are many risk factors for cataract development, including smoking, diabetes, ionizing radiation, eye injury or surgery, excessive UVB exposure, family history, and extended use of steroids.  However, the most important risk factor for cataract development is aging.  It is estimated that approximately 70 percent of Americans over the age of 75 have cataracts that result in impaired vision (Mayo Clinic).  Although the disease is considered “age-related”, it may be present in middle age and be diagnosed later in life when symptoms begin.

Cataract formation during aging

The lens is composed mainly of proteins and water.  The lens retains all its cells for the entire lifespan of the organism, and is completely clear at birth.  Protein turnover in the center of the lens is very slow; therefore, it is composed of very stabile proteins.  The predominant proteins in the lens belong to the crystallin family (alpha, beta and gamma).  Alpha crystallins have “chaperone” functions, which enable them to associate with other proteins.  These associations include binding to unfolded or aberrant proteins to prevent the formation of aggregates.  In the aging lens, chaperone activity of crystallins is decreased, allowing cataractogenesis to occur (2).

During the process of aging, crystallins undergo chemical modifications, such as oxidation.  Once chemically modified, these proteins are broken down into amino acids.  This process is inefficient, resulting in the accumulation of oxidized proteins (3).  Protein modifications can result in inappropriate protein interactions, causing clumping to occur (4).  Aggregates of chemically modified, damaged and partially unfolded crystallins may then form the cataract.  As the cataract enlarges, the light passing through the lens becomes more scattered, resulting in lens opacity and blurring of vision.   

Nutritional prevention studies

There is a great deal of interest in the role of antioxidants in the prevention of age-related diseases.  However, clinical data have shown limited promise thus far.  The Age-Related Eye Disease Study (AREDS), involving a 6 year treatment with high doses of vitamins C, E, and beta-carotene reported no apparent effect on the development or progression of age-related lens opacities in older, Caucasian American adult subjects (reviewed in 5).  Similarly, no effect was observed on cataract progression with these supplements in study subjects from a region of India with high cataract incidence (6).  The Food and Drug Administration has reviewed the findings of studies using supplementation with the carotenoids lutein and zeaxanthin and did not find sufficient evidence of prevention of cataract (7).  Despite the negative findings of these large-scale studies and reviews, there are numerous reports that suggest that high dietary antioxidant intake or supplementation is related to delayed progression of cataract (reviewed by the Foundation of the American Academy of Ophthalmology).  Discrepancies between study results may be attributed to differences in their design, methods, and subjects.  Despite conflicting reports, all would agree upon the benefits of a healthy diet.

References

1.     Foster A, Johnson GJ, 1990; Int Ophthalmol . 14:135–40.

2.     Kumar PA, Reddy GB, 2009; IUBMB Life 61(5):485-95.

3.     Sharma KK, Santhoshkumar P, 2009; Biochim Biophys Acta. 1790(10):1095-108.

4.     Takemoto L, Sorensen CM, 2008; Exp Eye Res. 87(6):496-501. 

5.     Chiu CJ, Taylor A, 2007; Exp Eye Res. 84(2):229-45.

6.     Gritz  DC, et al., 2006; Br J Ophthalmol. 90(7): 847–851.

7.     Fernandez MM, Afshari NA. 2008; Curr Opin Ophthalmol. 19(1):66-70.

Posted under: Cataract.

Tags: aging, antioxidants, Cataract

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

Hypertension is commonly referred to as high blood pressure. Blood pressure is the force exerted by the blood on the arterial walls. It is measured in millimeters of mercury, and consists of two parts, a top number (systolic) and a bottom number (diastolic). Systolic refers to the pressure during contraction of the heart, where blood is pumped out into the arteries. Diastolic is the pressure when the heart relaxes and fills with blood. Hypertension is usually asymptomatic. If left untreated, it can lead to stroke, heart attack, kidney disease and other problems.

The criteria for a diagnosis of hypertension defined by the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are as follows:

1. Blood pressure readings are taken after the patient has been seated quietly for 5 minutes.

2. The blood pressure cuff is the correct size and the arm is elevated with support to be level with the heart.

3. The patient must refrain from smoking, exercising, or consuming caffeine 30 minutes prior to the measurement.

4. Elevated blood pressure on two readings (average) per visit on two or more visits is suggested for diagnosis of hypertension.

The committee also classified blood pressure readings for adults:

Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42:1206–52.

The likelihood of having hypertension increases with age; it is estimated that more than 50% of people 65 and older have hypertension (American Geriatric Society). There are many contributing factors in the etiology of developing hypertension with aging. Many are due to physiologic changes that occur in the arteries that result in loss of elasticity. These include collagen accumulation and crosslinking, thinning of the elastic vessel components, calcium buildup and a decrease in smooth muscle cells (1). These structural changes are most evident in large arteries, like the aorta (2). The resulting thickening and a loss of elasticity leads to a decreased ability of the artery to respond to changes in blood flow occurring as the heart pumps. The impaired ability of the arteries to expand when blood is pumped out of the heart will elevate systolic blood pressure. Elevations in systolic blood pressure are now thought to be associated with adverse outcomes, such as stroke and heart attack.

Age-related hypertension is also related to salt-sensitivity, which tends to increase in aging. Approximately 60% of individuals with hypertension are physiologically sensitive to sodium intake. These individuals will have an increased blood pressure response to sodium, compared with those who are not sensitive. This is thought to be related to a decrease in the ability of the kidney to clear sodium from the body (3). Excess sodium retention may be due to decreased functioning of cellular sodium-potassium pumps (4) or an increase in substances that inhibit the action of sodium pumps (5). In some individuals, salt sensitivity may be due to inherited gene mutations. In women, decreased estrogen production after menopause is thought to increase salt sensitivity (6).

Hypertension is commonly treated with antihypertensives. However, lifestyle factors can be modified to lower blood pressure in hypertensive people.

1. Dao HH, Essalihi R, Bouvet C, et al. Cardiovasc Res 2005; 66: 307–17.

2. Mitchell GF, Parise H, Benjamin EJ, et al. Hypertension 2004; 43: 1239–45.

3. Epstein M, Hollenberg NK. J Lab Clin Med 1976; 87: 411–7.

4. Zemel MB, Sowers JR. Am J Cardiol 1988; 61(16): 7H–12H.

5. Anderson DE, Fedorova OV, Morrell CH, et al. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1248–54.

6. Colylewright M, Reckelhoff JE, Ouyang P. Hypertension 2008; 51: 952–9.

Posted under: Cardiovascular diseases, Hypertension.

Tags: aging, high blood pressure, Hypertension

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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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