Assistant Professor, Department of Internal Medicine, Division of Geriatrics
Adjunct Assistant Professor, Department of Physiology
VA Med.Center, SLC
GRECC Bldg 2 Rm 1D30
500 Foothill Drive
Salt Lake City, UT 84148
Office 801-582-1565 Ext 4-2046
Lab 801-582-1565 Ext 4-3361
Aging is amajor risk factor for the development of cardiovascular disease (CVD) and vascular endothelial dysfunction. Advancing age also increases the risk of metabolic disease such that 40% of Americans over age 65 present with type 2 diabetes (T2D) or impaired glucose tolerance. Likewise, overweight and obesity are associated with an increased risk of both CVD and T2D, and it is now estimated that approximately 60% of US adults are overweight/obese. In the midst of this epidemic rate of obesity, the population as a whole is steadily aging, with the percent of the US population over the age of 65 projected to increase to nearly 20% by the year 2030. The interaction of aging with obesity is little understood but will clearly present a significant clinical burden in our immediate future. As such, it is essential that we further our understanding of not only the mechanisms by which both aging and obesity act to independently increase disease risk but also the mechanisms by which their interaction leads to an exacerbation of disease risk in older individuals. My laboratory’s primary research focus is to understand the mechanisms by which aging modulates the susceptibility of the vascular and metabolic systems to the deleterious effects of high fat feeding and obesity.
1. Exploring the mechanisms that underlie increases in tissue inflammation that are associated with aging and high fat diet associated vascular and metabolic dysfunction and as well as determining the mechanisms by which increases in physical activity improve/prevent this dysfunction.
2. Examining the role that arterial and immune-cell specific cbl-associated protein (CAP) may play in mediating aging and high fat diet induced impairments in vascular endothelial function.
3. Determining the role that endothelial dysfunction in adipose tissue arteries may play in mediating dysregulation of lipid handling and systemic metabolic and vascular dysfunction as a consequence of aging and high fat feeding.
Donato AJ, KA Magerko, BR Lawson, JR Durrant, LA Lesniewski and DR Seals.SIRT-1 and vascular endothelial dysfunction with aging in mice and humans. J. Physiol., Jul 2011; 10.1113/jphysiol.2011.211219.
Lesniewski LA, JR Durrant, ML Connell, GD Henson, AD Black, AJ Donato, and DR Seals. Aerobic Exercise Reverses Arterial Inflammation with Aging in Mice. Am. J. Physiol. Heart Circ. Physiol., May 2011; 10.1152/ajpheart.01276.2010.
Lesniewski LA, JR Durrant, ML Connell, BJ Folian, AJ Donato, and DR Seals.Salicylate Treatment Improves Age-Associated Vascular Endothelial Dysfunction: Potential Role of Nuclear Factor kB and Forkhead Box O Phosphorylation. J Gerontol. A Biol. Sci. Med. Sci., Apr 2011; 66:409-18. PMC3055281
Edwards AG, AJ Donato, Lesniewski LA, RA Gioscia, DR Seals, and RL Moore. Life-long caloric restriction elicits pronounced protection of the aged myocardium: A role for AMPK. Mech. Ageing Dev., Nov 2010; 131: 739-42. PMC3010207
Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA, and DR Seals.Arterial stiffening with ageing is associated with transforming growth factor β 1-related changes in adventitial collagen: reversal by aerobic exercise. J. Physiol., Aug 2010; 10.1113/jphysiol.2010.194753.
Rippe C, Lesniewski LA, ML Connell, T Larocca, AJ Donato, and DR Seals.Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress. Aging Cell, Jan 2010; NIHMS185945
Seals DR, AE Walker, GL Pierce and Lesniewski LA. Habitual exercise and vascular aging.J. Physiol. Sep 2009; 10.1113/jphysiol.2009.178822.
Donato AJ, GL Pierce, Lesniewski LA and DR Seals.Role of NFkB in age-related vascular endothelial dysfunction in humans.AGING.Aug 2009; 1: 678-680.
Durrant JR, ML Connell, BJ Folian, MJ Russell, AJ Donato, DR Seals and Lesniewski LA. Voluntary wheel running restores endothelial function in conduit arteries of old mice: Direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J. Physiol. Jul 2009; 587: 3271-3285.
Pierce GL, Lesniewski LA, BR Lawson, SD Beske and DR Seals. Nuclear factor κ B activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans. Circulation.Mar 2009; 119: 1284-1292.
Lesniewski LA, ML Connell, JR Durrant, BJ Folian, MC Anderson, AJ Donato and DR Seals. B6D2F1 mice are a suitable model of oxidative stress-mediated impaired endothelium-dependent dilation with aging. J Gerontol. A Biol. Sci. Med. Sci., Jan 2009; 64A: 9-20.