About NIA

Fiscal Year 2006 Budget

Reducing Disease and Disability

About 79 percent of people age 70 and older have at least one of these seven potentially disabling chronic conditions—arthritis, hypertension, heart disease, diabetes, respiratory diseases, stroke, and cancer.9  Other chronic conditions can compromise the health and quality of life of older Americans, as well; for example, a recent study found that 11 percent of U.S. men and 10.2 percent of U.S. women over age 65, and fully 20 percent of Americans over age 85, have anemia. This condition, while usually treatable, is often under-diagnosed and can be associated with a number of adverse health outcomes.10 The burden of such chronic conditions is felt not only by individuals, but also by families, employers, and the health care system.  Research to improve understanding of the risk and protective factors for chronic disease and disability can lead to the development of effective prevention strategies. 

Treatment and Prevention of Disease

An Asthma Drug Improves Heart Function and Prevents Further Damage in Rats With Heart Disease. The β-adrenoreceptors (β-ARs) receive and react to nerve impulses in certain tissues throughout the body.  In the heart, there are at least three types of β-AR, each found primarily in a different type of cardiac tissue and each causing different effects when activated. Suppression of β1-adrenoreceptors through the use of “beta blockers” is a standard treatment for congestive heart failure, which currently affects around five million Americans,11 while drugs that stimulate β2-ARs act as vasodilators and are commonly used in asthma inhalers. In addition, laboratory studies have shown that continuous stimulation of β2-ARs protects heart cells from premature death.

NIH researchers have achieved promising results using a β2-AR stimulator in a rat model of heart disease. After inducing heart attacks in rats, they treated one group with a beta blocker, metaprolol, while additional groups received continuous treatment with one of two β2-AR stimulators, either fenoterol or zinterol. A final (control) group received no treatment. After six weeks, the rats' heart function was assessed and heart tissue was examined. The researchers found that the β2-AR stimulators were more effective than metaprolol in preventing further cell damage and death. In addition, treatment with fenoterol or zinterol, unlike metaprolol, was actually associated with improved heart function in the diseased rats. These results suggest that β2-AR stimulators, already widely in use for the treatment of pulmonary disease, may also be effective in the treatment of congestive heart failure.

Extended Outpatient Rehabilitation improves independence after hip fracture. Hip fractures are common in the elderly and can have a devastating impact on the ability of older patients to remain independent.  Despite standard rehabilitation, up to three-fourths of patients with hip fractures fail to regain their walking ability or functional status within six to twelve months of surgery. To determine whether additional rehabilitation would improve function following hip fracture in frail elders, researchers conducted a randomized controlled trial comparing extended outpatient rehabilitation that included resistance training, to the usual program of low intensity home exercise following surgery to repair a hip fracture. Men and women 65 years or older with a recent hip fracture (within 16 weeks of repair) were randomly assigned to either supervised physical therapy with whole-body progressive resistance exercise training or to a control group doing home exercise focusing primarily on flexibility. The outcome measures included physical performance tests, measures of functional status, and activities of daily living (ADL) over six months. Changes in physical performance and functional status over time were significantly better for the intervention group compared to the control group: patients in the intervention group showed greater improvements in muscle strength, walking speed, and balance than patients in the control group. These results indicate that extended outpatient rehabilitation with progressive resistance training improves physical function and mobility among frail elderly hip fracture patients. Compared to usual care for this patient population, this program promotes better return to prefracture function, reduces disability, and improves quality of life. 

Early-Life Determinants of Late-Life Health

A number of studies have investigated early-life determinants of later life health. For example, researchers have investigated the association of high blood pressure (BP) and hippocampal atrophy (HA) among Japanese-American men participating in the longitudinal community-based Honolulu Asia Aging Study (HAAS). The hippocampus is an area of the brain that is critical to learning and memory, and is vulnerable to vascular damage. The investigators found that men who had had high midlife BP, but had never been treated, had an increased risk for later HA compared with never treated men with normal midlife BP. In another study, researchers studying a cohort of young and middle-aged adults from a semirural black and white community in Bogalusa, Louisiana, examined the association between carotid wall thickness and traditional cardiovascular risk factors measured since childhood.  Increased arterial stiffness is a known predictor of cardiovascular-related diseases and death at middle and older ages, and carotid artery wall thickness is associated with cardiovascular risk factors and predicts atherosclerosis in middle- and older aged adults. They found that measures of LDL (“bad”) cholesterol and relative weight in childhood predicted carotid wall thickness in the adults, and that childhood blood pressure was a consistent predictor of arterial stiffness in adulthood. Recent research has pointed to a number of early life conditions that have far-reaching associations with a range of chronic conditions, including exposure to adverse conditions in utero, infectious diseases and environmental toxins, nutritional deficits, childhood poverty and stressful family conditions.  Earlier identification of risk factors that are associated with diseases that manifest later in life could lead to the development of earlier and better preventive strategies.

Elevated Levels of Homocysteine May be an Important but Modifiable Risk Factor for Osteoporosis. To test the hypothesis that increased blood homocysteine levels may be a risk factor for osteoporosis, the relationship between circulating homocysteine levels and later hip fractures was evaluated in 825 men and 1174 women, ranging in age from 59 to 91 years, from whom blood samples had been obtained years earlier. After a followup of 12.3 years for men and 15.0 years for women, there was a significantly greater risk of hip fracture for both men and women with high homocysteine compared to those with low levels—risk was increased in men and women by a factor of 4 and 1.9 respectively. Because homocysteine levels can be modified by diets or vitamin supplements with sufficient levels of vitamins such as folic acid, B6 and B12, such dietary strategies could reduce the burden of hip fractures in older individuals. 

Importance of Walking for Maintaining Mobility. In a recent study of community-dwelling women enrolled in the Women's Health and Aging Study, investigators found that functionally limited women ages 65 and older, who walked at least eight blocks per week outside their homes, were better able to maintain their functional capacity and walking ability than women who walked less or did not get out the door at all. This effect is independent of initial functional capacity, disease profile, health-related behaviors, and psychological and social-demographic factors. These results provide strong evidence that even a small amount of regular walking can help to maintain mobility.

Appetite and the Immune System: A New Model. Loss of appetite and decreased food intake are common among the seriously ill. Appetite regulation is complex and involves a number of factors; for example, appetite is suppressed by leptin, a protein found in fat cells, but stimulated by ghrelin, a recently identified hormone produced by stomach cells.  There is also increasing evidence that the immune system is involved, with immune-based proteins known as inflammatory cytokines acting on the nervous system to control appetite. NIH researchers have recently found that, in addition to stomach cells, ghrelin is produced in certain immune cells, along with its receptor protein, GHS-R. When ghrelin binds to GHS-R, the result is inhibition of inflammatory cytokines associated with appetite loss. They further found that leptin increases cytokine activity, while also spurring increased expression of GHS-R by T-lymphocytes, a different type of immune cell. These findings provide a model of how ghrelin and leptin work together to control immune cell activation and inflammation with regard to the appetite, and also suggest that drugs that stimulate ghrelin/GHS-R may be useful in the management of wasting associated with chronic disease.

  1. National Center for Health Statistics. Health, United States, 1999 with Health and Aging Chartbook.  Figure 11, pg. 41. Hyattsville, MD:  1999.
  2. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, and Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: Evidence for a high rate of unexplained anemia. Blood  104:  2263-2268, 2004.
  3. Data are from the National Center for Health Statistics. See Morbidity & Mortality: 2004 Chart Book on Cardiovascular, Lung, and Blood Diseases. National Heart, Lung, and Blood Institute, 2004.