Candidate: The candidate plans a career as an independent clinical investigator focusing on patient-oriented research in sleep disorders with an emphasis on the biology of aging. Environment: Harvard University provides a superb environment for this award. The Sleep Disorders Laboratories and Hebrew Rehabilitation Center for Aging have extensive expertise in sleep physiology and the biology of aging respectively. Didactic training and research seminars will be provided through the School of Public Health, HRCA, and the HMS Division of Aging. Research: OSA is a common disease with substantial morbidity. Recent data suggest that OSA has major neurocognitive and cardiovascular sequelae, with the elderly being particularly predisposed. Sleep apnea pathogenesis likely involves abnormalities in upper airway anatomy, pharyngeal dilator muscle dysfunction, ventilatory control instability and other factors. To date, little is known about the influence of aging on sleep apnea pathogenesis, since few investigators have assessed these variables in combination using state of the art techniques. We plan to perform a cross sectional study evaluating all variables known to be important in apnea pathogenesis. We will study both older and younger individuals with known OSA, as well as age-matched controls. We will study 20 subjects/patients from each of these 4 categories to assess the impact of aging on the variables of interest. We plan to use statistical techniques to perform multivariate analyses using anatomical and physiological variables to predict pharyngeal mechanics. Furthermore, we are developing a computational (finite element) model to assess the effect of various factors on pharyngeal mechanics. We plan to determine the variables most influenced by aging and use the statistical and computational modeling techniques to assess how they impact pharyngeal mechanics. In so doing, we will identify potential targets for intervention to reduce the sequelae of sleep apnea in the elderly. The principal investigator will continue didactic training in the biology of aging to complement previous training in respiratory physiology. As well, he has joined the Division of Aging at Harvard Medical School and will regularly attend research seminars and conferences in order to further understand the aging process. Furthermore, he will attend national meetings dedicated to the pursuit of aging mechanisms and geriatric medicine. Ultimately, our goal is to improve our understanding of the aging mechanisms underlying the development of sleep apnea, as well as to improve the quality of life of elderly patients who are either afflicted with sleep apnea or at risk of its occurrence.
| Czerwi?ska, Jolanta; Nowak, Ma?gorzata; Wojtczak, Patrycja et al. (2018) ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation. Free Radic Biol Med 124:79-96 |
| Sands, Scott A; Owens, Robert L; Malhotra, Atul (2016) New Approaches to Diagnosing Sleep-Disordered Breathing. Sleep Med Clin 11:143-52 |
| Kezirian, Eric J; Goding Jr, George S; Malhotra, Atul et al. (2014) Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes. J Sleep Res 23:77-83 |
| Bakker, J P; Balachandran, J S; Tecilazich, F et al. (2013) Pilot study of the effects of bariatric surgery and continuous positive airway pressure treatment on vascular function in obese subjects with obstructive sleep apnoea. Intern Med J 43:993-8 |
| Malhotra, Atul; Drazen, Jeffrey M (2013) High-frequency oscillatory ventilation on shaky ground. N Engl J Med 368:863-5 |
| Eikermann, M; Eckert, D J; Chamberlin, N L et al. (2010) Effects of pentobarbital on upper airway patency during sleep. Eur Respir J 36:569-76 |
| Eckert, Danny J; Malhotra, Atul; Jordan, Amy S (2009) Mechanisms of apnea. Prog Cardiovasc Dis 51:313-23 |
| Eckert, Danny J; Malhotra, Atul; Lo, Yu L et al. (2009) The influence of obstructive sleep apnea and gender on genioglossus activity during rapid eye movement sleep. Chest 135:957-964 |
| Saboisky, Julian P; Chamberlin, Nancy L; Malhotra, Atul (2009) Potential therapeutic targets in obstructive sleep apnoea. Expert Opin Ther Targets 13:795-809 |
| Rahangdale, Shilpa; Yeh, Susie Yim; Malhotra, Atul et al. (2009) Therapeutic interventions and oxidative stress in diabetes. Front Biosci (Landmark Ed) 14:192-209 |
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