Age-related olfactory loss is an important public health problem affecting approximately 14 million older Americans. The profound burden this sensory impairment causes in the daily lives of older people is associated with a substantially decreased quality of life, affecting critical functions such as safety, nutrition, sensation of pleasure, and general well-being. Because olfaction declines over time, the clinical impact will increase as our population ages. Previous studies of this decline in olfactory physiology in humans have been limited, requiring novel approaches to understanding factors that affect this process. In this application, I propose to characterize factors that underlie susceptibility to ag-related olfactory decline. Using data from the Memory and Aging Project (MAP) and the National Social Life, Health, and Aging Project (NSHAP), I plan to identify biodemographic factors that are associated with age-related olfactory decline. These robust resources, in which health and olfactory data have been collected previously along with relevant biomeasures, will allow an analysis of medical and psychosocial parameters that are associated with olfactory loss in older persons. In parallel, I will examine genetic risk factors for this phenotype by performing genome-wide association studies (GWAS) using existing genotype data in MAP and in the Hutterites, a population which has a number of distinct advantages for genetic mapping, including uniform environmental exposures and rich clinical information on relevant co-morbidities. This line of study will involve analysis of several olfactory traits for identifying gene(s) involved in the decline of the sense of smell. Lastly, using available, high quality DNA specimens, I will replicate these genetic associations in NSHAP. A structured training program will include courses in genetic epidemiology and demography for the development of analytic expertise, culminating in a Master's degree. Mentorship will be multidisciplinary by three renowned scientists who possess significant experience in genetics, demography, and aging. This award will allow me to develop the skills necessary to direct an independent research program on the impact of olfactory decline and other nasal diseases on older persons. This approach, utilizing three unparalleled and complementary data sets, will provide insight into the pathophysiology of age-related olfactory decline which, ultimately, can lead to improved prognostic, diagnostic and therapeutic modalities. Completion of these studies will serve as a model for understanding the non- genetic and genetic influences on sensory decline in aging.

Public Health Relevance

This proposal describes multiple approaches to understanding why the sense of smell decreases with age, a burdensome problem for millions of older persons. Through analyses in three well-characterized groups of older individuals, each with unique advantages for study, Dr. Pinto will examine both clinical and genetic factors that predispose to olfactory decline in aging. Additionally, with training in demography, gerontology, and genetics supported by this award, Dr. Pinto will develop new scientific skills in this arena with wide applicability to future work, allowing for a productive career in geriatric otolaryngolog.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG036762-03
Application #
8659328
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Chen, Wen G
Project Start
2012-04-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
$148,566
Indirect Cost
$11,005
Name
University of Chicago
Department
Surgery
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Dong, Jing; Wyss, Annah; Yang, Jingyun et al. (2017) Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans. Mol Neurobiol 54:8021-8032
Igartua, Catherine; Davenport, Emily R; Gilad, Yoav et al. (2017) Host genetic variation in mucosal immunity pathways influences the upper airway microbiome. Microbiome 5:16
Correia, Camil; Lopez, Kevin J; Wroblewski, Kristen E et al. (2016) Global Sensory Impairment in Older Adults in the United States. J Am Geriatr Soc 64:306-313
Ajmani, Gaurav S; Suh, Helen H; Wroblewski, Kristen E et al. (2016) Fine particulate matter exposure and olfactory dysfunction among urban-dwelling older US adults. Environ Res 151:797-803
Ajmani, Gaurav S; Suh, Helen H; Pinto, Jayant M (2016) Effects of Ambient Air Pollution Exposure on Olfaction: A Review. Environ Health Perspect 124:1683-1693
Sivam, Anita; Wroblewski, Kristen E; Alkorta-Aranburu, Gorka et al. (2016) Olfactory Dysfunction in Older Adults is Associated with Feelings of Depression and Loneliness. Chem Senses 41:293-9
Adams, Dara R; Ajmani, Gaurav S; Pun, Vivian C et al. (2016) Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older U.S. adults. Int Forum Allergy Rhinol 6:1245-1252
Pinto, Jayant M; Wroblewski, Kristen E; Kern, David W et al. (2015) The Rate of Age-Related Olfactory Decline Among the General Population of Older U.S. Adults. J Gerontol A Biol Sci Med Sci 70:1435-41
Garneau, Jonathan; Ramirez, Michael; Armato 3rd, Samuel G et al. (2015) Computer-assisted staging of chronic rhinosinusitis correlates with symptoms. Int Forum Allergy Rhinol 5:637-642
Kern, David W; Schumm, L Philip; Wroblewski, Kristen E et al. (2015) Olfactory thresholds of the U.S. Population of home-dwelling older adults: development and validation of a short, reliable measure. PLoS One 10:e0118589

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