Areas of Interest
Aging is the progressive increase of physiological deterioration leading to impaired organ function and is a primary risk for degenerative diseases, including both sporadic cases and those with genetic underpinnings. Aging is universal to all living species and it has always been assumed that it is unavoidable. In recent years, however, the science of aging has demonstrated unequivocally that the development of aging is controlled by biomolecular and genetic pathways. At the Center for Healthy Aging, we will work on several areas of interest. These include:
Geroscience, the field of aging research, which aims to understand, and potentially alter, how fundamental biological processes lead to age-related changes, has exploded in recent years due to advances at Stony Brook and other institutions. For example, researchers at SBU are examining ways to control senescent cells (cells that deteriorate with age), which accumulate with age in various tissues and play a causal role in chronic diseases such as diabetes, cancer, osteoarthritis and Alzheimer’s disease. SBU has considerable strengths in research into the biology of cellular senescence, the impact of endogenous viruses in mediating inflammatory pathways of senescent cells, and in imaging inflammatory signaling and metabolic dysfunction within tissues. The CHA will support a vibrant program of geroscience research and is already leveraged by substantial federal funds. Convergence of existing expertise relating to aging, including DNA damage, endogenous retroviruses, inflammaging, immunology, metabolism and neurodegenerative diseases that are the main pillars of geroscience, will be the cornerstone of the CHA. In addition to the existing research strengths, the CHA will also be leveraged by state-of-the-art imaging facilities, including MRI and PET.
Representative microscope images of human brain slices of the substantia nigra pars compacta derived from age-matched control individual or sporadic Parkinson’s patients. Tyrosine hydroxylase (TH, green) labels dopaminergic neurons, p21 (magenta) is a marker for senescence. In summary, this figure shows evidence of cellular senescence in the most relevant nerve cells in Parkinson’s disease. Senescence can be seen as molecular biological aging and is characterized by gradual deterioration of functional characteristics in living organisms. It is thought that accumulation of senescent cells leads to “inflammaging” and generally causes age-related symptoms. Age-related senescence will cause a local inflammation leading to spreading and ultimately loss of nerve cells which causes Parkinson’s disease. The discovery of this kind of “inflammaging” is novel in Parkinson’s and has potential for new therapeutic interventions to stop progression of the disease. (Images from Riessland et al., Cell Stem Cell 2019).
Representative images of human stem cell-derived dopaminergic neurons. These nerve cells are the affected cells in Parkinson’s disease. Blue staining positive cells are senescent neurons. The senescent cells on the right are cells that were depleted for the Parkinson’s risk gene SATB1. In summary, this data shows that dopamine neurons are capable of entering a state of senescence which could lead to midbrain “inflammaging”. (Images from Russo (unpublished) and Riessland et al., Cell Stem Cell 2019).
Stony Brook has unique imaging resources that will be a central focus of the CHA. Positron Emission Tomography (PET) is an imaging technique using positron labeled molecules of very low mass to image and measure molecular targets. Using PET imaging for a given molecule of interest (e.g., markers of inflammation), the following can be determined: 1) the quantity of the target, 2) its distribution throughout the body, 3) feasibility of a new pharmaceutical, 4) the pathophysiology of disorders affecting that target, and 5) the level of target engagement needed for treatment response (treatment outcome prediction).
Brain PET, in particular, has received much interest in recent years due to the importance of PET in neurodegenerative and psychiatric disorders, and is uniquely suited for aging research.
SBU has world-class PET imaging facilities, including two research dedicated PET scanners, a simultaneous PET/MRI and a preclinical PET imaging facility, allowing quantification of targets in rodents, non-human primates, and humans. The facility can synthesize PET tracers that target acetylcholine, amyloid, dopamine, glutamate, serotonin, metabolism, and inflammation. Further, with experts in PET tracer development, the ability to design and synthesize new PET tracers to examine targets previously unseen in vivo can be offered to CHA investigators. Stony Brook is one of the few institutions in the world that can perform full quantification of these targets. With these services, a major goal for the CHA will be to expand the application of PET to aging research in the brain and other tissues.
The RSOM has a large geriatric clinical practice that includes ambulatory and inpatient services, outreach programs to nursing and rehabilitation centers in our area, including the Long Island State Veterans Hospital on the Stony Brook University campus, and a program on translational research and geriatric care.
The Center of Excellence for Alzheimer’s Disease serves more than 54,000 patients on Long Island suffering from Alzheimer’s disease and related dementias. In addition, Stony Brook Medicine has achieved designation as an Age Friendly Health System by the Institute for Healthcare Improvement and is working to improve care related to geriatrics.
The Health Resources Services Administration awarded a $10 million grant to SBM to create inpatient research capacity. With these existing outstanding clinical programs, the CHA represents a unique opportunity for faculty to address the basic and clinical science of the multi-system decline of physiologic systems with aging; develop unique, interdisciplinary strategies to study our aging patients; and reach out to the community to develop services that will enhance the quality of life of our elderly population.
The science of mobility has been identified as a new research opportunity that would be inclusive of our medical specialties, other schools of the health sciences and the university. An integrated, multidisciplinary approach to understanding factors that contribute to reduced mobility may help to target interventional strategies or environmental modifications to reduce the occurrence of falls, which are a major cause of morbidity and mortality in older individuals.
With age, diseases such as macular degeneration, diabetic neuropathy, osteoporosis and sarcopenia, as well as age-related declines in hearing, diminish the quality of the integrated sensory input systems critical to stability. Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s undermine the ability to perceive, process and respond to environmental cues, increasing fall risk. As such, when translated to the clinic, Stony Brook’s research endeavors, focusing on reducing age-related decline/disease through multidisciplinary approaches will also result in a reduction of falls.
Inevitably, fall risk is ultimately a complex amalgam of many different system inputs that will involve, initially, geriatrics, orthopedics, ophthalmology, neurology, radiology, lifestyle medicine, nutrition and nursing. Mobility, as a theme for the CHA is ideal for population-based studies and for extending our clinical research to elderly patients in their own homes.
The CHA represents an unprecedented continuum of research and patient care. The combination of these unique assets will help formulate a one-of-a kind academic partnership that will offer education and training opportunities leading to increased competitiveness for additional federal and state funding, synergize with the Long Island Network for Clinical and Translational Science (LINCATS), and provide a competitive edge for Program Project Grants at the NIA.
