The candidate, Lisa A. Lesniewski Ph.D., is a physiologist in the Department of Integrative Physiology at the University of Colorado at Boulder. Dr. Lesniewski's research focuses on the mechanisms mediating vascular and metabolic dysfunction with aging and how habitual aerobic exercise can preserve physiological function with aging. Her immediate goal is to acquire new research and professional skills that will help her to achieve her long-term career goal of developing a successful independent, extramurally-funded research program on the prevention and treatment of vascular and metabolic aging. The proposed KO1 award will provide Dr. Lesniewski the necessary support to achieve this goal. CAREER DEVELOPMENT PLAN. Dr. Lesniewski's research career development training activities will consist of: 1) acquiring new research skills associated with and complementary to the proposed research plan;and 2) structured activities including formal course-work, attendance and presentations at weekly journal clubs, university seminar series and scientific meetings, and regular interactions with her mentoring team. ENVIRONMENT. The environment for Dr. Lesniewski's training should be outstanding. The sponsor, Dr. Douglas Seals, is a well-established extramurally-funded scientist with a strong record of successful mentoring in biomedical aging research. He is complemented by a group of consulting mentors that consist of internationally- recognized investigators, each providing specific expertise in a key area of Dr. Lesniewski's research project and overall training plan. RESEARCH.
The aims of the research project are to establish if aging increases susceptibility to the deleterious effects of a high fat, or Western diet (WD) by exacerbating chronic low grade inflammation and to determine if habitual exercise can prevent the deleterious effects of WD on vascular and metabolic function by reducing inflammation. The proposed research will use an """"""""integrative"""""""" (system to gene) approach in young, middle-aged, and older mice to identify the cellular and molecular mechanisms by which WD causes inflammation-associated endothelial and metabolic dysfunction with aging and regular exercise exerts protective effects. The results should provide clinically important information regarding: 1) the influence of aging in altering vulnerability to a commonly encountered factor, WD and 2) the mechanisms by which WD causes and habitual exercise prevents these deleterious effects.
Advancing age and consumption of a WD are associated with vascular and metabolic dysfunction and disease. However, it is unknown if the adverse effects of WD become greater with aging, the mechanisms by which this occurs, and if these effects can be prevented by habitual aerobic exercise.
|Donato, Anthony J; Henson, Grant D; Hart, Corey R et al. (2014) The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction. J Physiol 592:4083-96|
|Walker, Ashley E; Henson, Grant D; Reihl, Kelly D et al. (2014) Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries. Age (Dordr) 36:559-69|
|Seals, Douglas R (2014) Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries. J Appl Physiol (1985) 117:425-39|
|Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R (2014) Aerobic exercise and other healthy lifestyle factors that influence vascular aging. Adv Physiol Educ 38:296-307|
|Morgan, R Garrett; Ives, Stephen J; Walker, Ashley E et al. (2014) Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J Hypertens 32:1293-9|
|Morgan, Richard G; Ives, Stephen J; Lesniewski, Lisa A et al. (2013) Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries. Am J Physiol Heart Circ Physiol 305:H251-8|
|Davis 3rd, Robert T; Stabley, John N; Dominguez 2nd, James M et al. (2013) Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation. J Appl Physiol (1985) 114:808-15|
|Donato, Anthony J; Walker, Ashley E; Magerko, Katherine A et al. (2013) Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell 12:772-83|
|Lesniewski, Lisa A; Zigler, Melanie C; Durrant, Jessica R et al. (2012) Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanism. Mech Ageing Dev 133:368-71|
|Donato, Anthony J; Henson, Grant D; Morgan, R Garrett et al. (2012) TNF-ýý impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity. Am J Physiol Heart Circ Physiol 303:H672-9|
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