Associate Professor, Department of Internal Medicine, Division of Geriatrics
Adjunct Associate Professor, Department of Nutrition and Integrative Physiology
Click Here for Dr. Lesniewski’s CV
VA Med.Center, SLC
GRECC Bldg 2 Rm 2D08
500 Foothill Drive
Salt Lake City, UT 84148
Office 801-582-1565 Ext 4-2046
Lab 801-582-1565 Ext 4-3361
The age of the US population is steadily increasing as is the prevalence of overweight and obesity, and both aging and obesity are primary risk factors for cardiovascular and metabolic diseases. My laboratory’s broad research interest is to understand the mechanisms underlying vascular and metabolic dysfunction and disease with advancing age as well as to understand how this is exacerbated by overweight/obesity.
Ongoing Research Projects:
Effects of Aging and Obesity on the Adipose Tissue and its Vasculature:
While once thought of as a merely a storage site for energy, the adipose tissue is now recognized as an endocrine organ that plays a central role in metabolic dysfunction in obesity. The adipose also demonstrates dysfunction with advancing age and may contribute to both vascular and metabolic disease by dysregulating lipid handling and contributing to systemic inflammation.
My laboratory is interested in elucidating both the role that adipose tissue dysfunction may play in age-associated vascular and metabolic dysfunction and the mechanisms by which aging and obesity lead to dysfunction in the adipose tissue and its associated vasculature. In particular, we are exploring the role of telomere dysfunction and cellular senescence and dysregulated signaling through the small GTPase, ARF6, in these processes.
Effects of Aging on Arterial Function and Atherosclerosis:
Advancing age is associated with vascular dysfunction and increased risk of cardiovascular diseases such as atherosclerosis, although the underlying mechanisms are incompletely understood. My laboratory seeks to elucidate the role of mTOR, miR-92a and ARF6 in age associated arterial dysfunction and atherosclerosis.
Inhibition of mTOR with rapamycin has been demonstrated to increase lifespan in mice, suggesting that mTOR activation with aging may play a central role in the aging process. My laboratory seeks to elucidate the role of altered mTOR signaling in the vascular aging phenotype and to explore the use of novel interventions that can mimic the beneficial effects of rapamycin.
MicroRNAs (miRs) are small noncoding RNAs that regulate translation of messenger RNA and have important physiological effects, acting on multiple gene targets often related to a specific cellular process/signaling pathway. MiR-92a, a member of the miR-17-92 cluster, is important in vascular growth during development and tumorogenesis and is decreased in advanced age. Our laboratory seeks to determine if an age-associated reduction in microRNA, miR-92a and its cluster miR-17-92, underlies age-associated arterial dysfunction and accelerated atherosclerotic.
Age-associated chronic inflammation is implicated in both arterial dysfunction and atherosclerosis. Activation of the small GTPase, ADP ribosylation factor 6 (ARF6), is associated with inflammatory states, but the impact of aging on arterial ARF6 is not known. Because ARF6 is also known to be sensitive to changes in shear stress, we seek to determine if ARF6 signaling modulates endothelial function, inflammation and mechanotransduction of turbulent / oscillatory shear and contributes to the development of age-related pro-atherosclerotic arterial dysfunction.
|Henson GD, Walker AE, Reihl KD, Donato AJ, Lesniewski LA (2014). Dichotomous mechanisms of aortic stiffening in high-fat diet fed young and old B6D2F1 mice. Physiol Rep, 2(3), e00268.|
|Walker AE, Henson GD, Reihl KD, Nielson EI, Morgan RG, Lesniewski LA, Donato AJ (2014). Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries. Age (Dordr), 36(2), 559-69.|
|Morgan RG, Ives SJ, Walker AE, Cawthon RM, Andtbacka RH, Noyes D, Lesniewski LA, Richardson RS, Donato AJ (2014). Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J Hypertens, 32(6), 1293-9.|
|Donato AJ, Henson GD, Hart CR, Layec G, Trinity JD, Bramwell RC, Enz RA, Morgan RG, Reihl KD, Hazra S, Walker AE, Richardson RS, Lesniewski LA (2014). The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction. J Physiol, 592(Pt 18), 4083-96.|
|Donato AJ, Lesniewski LA, Stuart D, Walker AE, Henson G, Sorensen L, Li D, Kohan DE (2014). Smooth muscle specific disruption of the endothelin-A receptor in mice reduces arterial pressure, and vascular reactivity and affects vascular development. Life Sci, 118(2), 238-43.|
|Gibson CC, Davis CT, Zhu W, Bowman-Kirigin JA, Walker AE, Tai Z, Thomas KR, Donato AJ, Lesniewski LA, Li DY (2015). Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium. PLoS ONE, 10(10), e0140370.|
|Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY (2015). Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 131(3), 289-99.|
|Walker AE, Henson GD, Reihl KD, Morgan RG, Dobson PS, Nielson EI, Ling J, Mecham RP, Li DY, Lesniewski LA, Donato AJ (2015). Greater impairments in cerebral artery compared with skeletal muscle feed artery endothelial function in a mouse model of increased large artery stiffness. J Physiol, 593(8), 1931-43.|
|Walker AE, Morgan RG, Ives SJ, Cawthon RM, Andtbacka RH, Noyes D, Lesniewski LA, Richardson RS, Donato AJ (2016). Age-related arterial telomere uncapping and senescence is greater in women compared with men. Exp Gerontol, 73, 65-71.|
|Lesniewski LA, Seals DR, Walker AE, Henson GD, Blimline MW, Trott DW, Bosshardt GC, LaRocca TJ, Lawson BR, Zigler MC, Donato AJ (2016). Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways.LID – 10.1111/acel.12524 [doi]. (Epub ahead of print) Aging Cell.|
|Hazra S, Henson GD, Morgan RG, Breevoort SR, Ives SJ, Richardson RS, Donato AJ, Lesniewski LA (2016). Experimental reduction of miR-92a mimics arterial aging. Exp Gerontol, 83, 165-70.|