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ARRA Investments in Research on Inflammation and Aging


Public Health Burden
Inflammation is a natural and highly regulated response that provides protection and promotes healing when infection or injury occurs. However, inflammatory processes, especially those mediating chronic inflammation, have been implicated as predictors or initiators of or contributors to chronic diseases and conditions of aging including cardiovascular disease, osteoarthritis, osteoporosis, Alzheimer's disease, insulin resistance and diabetes, muscle wasting, and frailty. The underlying biology connecting mediators of inflammation with these various age-related disease processes and conditions is unclear.

Preventing Neuroinflammation
The role of neuroinflammation, particularly chronic inflammation of the brain in the development of age-related neurodegenerative diseases such as Alzheimer’s disease (AD), has become a major focus for many researchers. The ability to counteract inflammatory processes in the brain could prevent or delay the onset of neurodegenerative diseases such as AD. ARRA funds are helping researchers accelerate their efforts to better understand the course of inflammatory processes in Alzheimer’s disease in the hopes of preventing or delaying cognitive decline and other more severe AD symptoms. For example, researchers are working to:  
  • Extend observations of participants in the NIH Alzheimer’s Disease Anti-inflammatory Prevention Trial to further elucidate the long-term effects of non-steroidal anti-inflammatory drugs and their ability to reduce cognitive decline and the incidence of AD dementia.1
  • Develop a safe and effective vaccine for the treatment of Alzheimer’s disease that will not cause an inflammatory response in the brain as previously experienced in an earlier clinical trial.  This novel approach holds significant promise for the development of future AD vaccines.2
Addressing Health Disparities and Social Stress
Many of the disparities in adult health and life expectancy across national, racial, occupational, and social class boundaries are well documented, but causal mechanisms are less well understood. Research to understand the biological functioning among diverse populations such as stress and its impact on inflammatory responses will be critical to the development of behavioral and public health interventions and to the elimination of these disparities. Investigators are using ARRA support to further understand the biological factors associated with health disparities. For example, in one project using Grand Opportunity funding, researchers are working to:
  • Better understand how race-based social stress, racial/ethnic identity, and biological functioning, including inflammation and the inflammatory system, contribute to health and healthy aging by studying participants in the Maryland Adolescent Development in Context Study, a nationally-recognized 17- year longitudinal study of family, school, neighborhood, and peer influences on the healthy and successful development of early adolescents and their families.  The population under study includes an oversampling of African Americans who are known to experience health disparities across these measures.3
Reducing Inflammation and Cardiovascular Disease Risk through Exercise
Research has shown that regular exercise reduces cardiovascular disease risk by suppressing inflammatory processes and reducing oxidative stress that can cause significant cellular damage. However, more research is needed to examine the link between exercise and the underlying mechanisms that cause a reduction in inflammation and oxidative stress. ARRA funds are being used to compare the effects of each of these mechanisms separately combined with an aerobic exercise program. Researchers are working to:
  • Examine the molecular and cellular pathways of  non-steroidal anti-inflammatory drugs such as salsalate or anti-oxidants such as vitamin C that may be responsible for exercise induced improvements in vascular functioning, which could help physicians identify the most effective treatment approach for reducing risk of cardiovascular disease, and could potentially prove beneficial for other age-related diseases that are improved with exercise.4
Inflammation and Osteoporotic Fractures
Osteoporosis is a disease that weakens bones to the point where they break easily – most often bones in the hip, backbone (spine), and wrist. It is called the “silent disease” because the loss of bone and bone mass may not be noticed until a bone breaks. Growing evidence suggests that there is a strong link between inflammation and the “remodeling” that accompanies bone erosion.
  • With ARRA support, several investigators are expanding their work in the Study of Osteoporotic Fractures (SOF) to examine whether renal function, inflammation, and vitamin D are important to maintaining and achieving higher levels of physical function and lower risks of falls and hip fractures.  Additional funding for SOF Clinical Centers will also allow investigators to implement public data sharing to allow other investigators direct access to data that can be used for other studies.5
Understanding Inflammation
As people age, their immune systems decline, resulting in dysfunction of inflammatory responses. Investigators are studying how chronic inflammation accelerates the aging process causing changes to skin, tissues, organs, and biological systems. With the availability of ARRA funds, investigators are working to describe more fully the underlying biology connecting the mediators of inflammation with different age-related disease processes and conditions. Their goal is to:
  • Investigate how neuronal nicotinic receptors (nAChR), that help cells throughout the body regulate normal inflammatory responses, contribute to regulating inflammation, especially as people age and to determine if changes in nAChR expression shape the progression of normal aging of the skin by altering the important balance between normal and excessive inflammation.6



  1. 1U01AG015477-06A2 -- Prevention of Alzheimer Dementia and Cognitive Decline -- John C. S. Breitner (WA)
  2. 3R01AG020159-08S1 -- Mucosal Abeta Vaccination: Modulating the Immune Response -- Cynthia Lemere (MA)
  3. 1RC2AG036780-01 -- Race-Based Social Stress and Health Trajectories from Adolescence to Adulthood -- Jacquelynne Eccles (MI)
  4. 3R01AG031141-01A1S1 -- Reduced Inflammatory Suppression of EDD with Habitual Exercise in Older Adults -- Douglas R. Seals (CO)
  5. 2R01AG027576-25 -- Study of Osteoporotic Fractures -- Pittsburgh Clinical Center -- Jane Cauley (PA); 2R01AG005394-25 -- Study of Osteoporotic Fractures -- Kristine Ensrud (MN); 2R01AG027574-25 -- Study of Osteoporotic Fractures -- Portland Clinical Center -- Teresa A. Hillier (OR)
  6. 3R01AG029838-02S1 -- Peripheral Nicotinic Cholinergic and Inflammatory Dysfunction in Aging -- Lorise Gahring (UT)


 
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