Currently, there are no treatments with significant disease modifying impact for major neurodegenerative diseases including Alzheimer?s disease and Parkinson?s disease. These diseases, even in their rare, autosomal dominant forms, are age-dependent, with age presenting the key risk factor for all sporadic forms of disease. Because the aging brain becomes increasingly vulnerable to neurodegeneration, slowing or reversing aspects of aging could therefore have a tremendous impact on the incidence and prevalence of these diseases. With a rapidly aging population, including aging Veterans pushing the boundaries of what our health care systems can absorb, there has been an unprecedented interest in aging and longevity from the public, funding agencies, and industry. Interestingly, studies of rodents and humans suggest that interventions targeted to individual organs or tissues, including muscle (e.g. through exercise), gut (e.g. through modifications of diet and the microbiome), and immune system (e.g. by reducing inflammation), can affect organismal aging. But how these organs may regulate aging processes is unknown. Dr. Wyss-Coray?s discoveries along with those of others indicate that the phenotypic age of individual organs is malleable and can be altered by exposing the organism to the systemic environment of an organism of a different age through heterochronic parabiosis or plasma transfer. Unexpectedly, Wyss-Coray recently found that heat-labile factors in blood plasma from young mice or young humans are sufficient to slow or reverse brain aging in mice. Conversely, factors in plasma from old mice or old humans can accelerate aspects of brain aging and cognitive impairment in mice. These surprising observations point in a new direction and prompted Dr. Wyss-Coray to study brain aging from a physiological, top-down perspective. Dr. Wyss-Coray is using chemical, bio-orthogonal manipulation of organisms, cutting edge proteomics, and next generation sequencing to answer how young blood revitalizes the old brain at the molecular level and to harness these processes towards reversing age-related changes and Alzheimer?s disease in the human brain. The goal of these studies is to develop new treatments for Veterans and patients with neurodegenerative diseases.

Public Health Relevance

According to the National Center for Veterans Statistics, 53% of Veterans, or roughly 9.86 million men and women were older than 65 in 2016. In 1992 only 26% were in that age group. With this dramatic increase in the aged population, there has been a profound increase in age- associated diseases with Alzheimer's disease taking the lead. According to statistics from the Alzheimer's Association an estimated one million, or 20% of all AD cases in the US are Veterans. This clearly is a major challenge to the scientific community and health professionals alike and I believe the novel research approach my group has taken can help in identifying possible therapeutic targets for neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Project #
5IK6BX004599-02
Application #
9911974
Study Section
Special Emphasis Panel (ZRD1)
Project Start
2019-04-01
Project End
2020-07-31
Budget Start
2020-04-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Veterans Admin Palo Alto Health Care Sys
Department
Type
DUNS #
046017455
City
Palo Alto
State
CA
Country
United States
Zip Code
94304