This competitive renewal of R01 AG07004 continues our systematic investigations into mechanisms underlying altered thermoregulatory control of skin blood flow (SkappaBF) with primary human aging, and the consequences thereof. Both cutaneous vasodilation (VD) in response to hyperthermic stimuli and cutaneous vasoconstriction (VC) in response to hypothermic stimuliare significantlyattenuated in aged skin. The previous funding cycle involved a systematic investigation of the mechanisms related to altered cutaneous VD in older men and women (briefly summarized in Section C of this proposal). The next sequence of proposed studies is the logical extension of this line of investigation, i.e., examining the mechanisms and consequences of altered cutaneous VC in aged skin, since (1) primary aging is associated with both a larger decrease in core temperature with cold stress and an increased incidence of clinical hypothermia, (2) these untoward outcomes are primarily the result of a relative inability to vasoconstrict the skin vasculature leading to an increased core-to-skin heat transfer, (3) several plausible sites of age-related changes exist in the efferent VC control pathway which have not been tested in vivo. Furthermore, older men and women with a low body mass and lean muscle mass are at ever) greater risk of hypothermia because of the combined effects of reduced VC and decreased core-to-skin thermal resistance.
Specific Aims 1 -3 examine basic efferent mechanisms of attenuated reflex VC in aged skin at the sympathetic nerve transmission, neurotransmitter/receptor, and end-organ response levels, respectively. These studies make use of new and recently refined techniques that allow for the in vivo examination of age-related changes in human skin.
Specific Aim 1 quantifies the skin sympathetic nerve activity (SSNA) during progressive skin cooling in older vs. young men and women and its relation to VC.
Specific Aim 2 addresses the relative contributionsof noradrenergic and nonnoradrenergic mechanisms in reflexVC inyoung and older subjects. Follow-up experiments are described that will determine the potential role of neuropeptide Y in this age-specific VC response.
Specific Aim 3 will examine the dose response characteristics of noradrenergicVC to assess the responsiveness of the aged cutaneous vasculature to norepinephrine. Finally, Specific Aim 4 involves a series of whole-body chamber experiments designed to determine and model the effects of altered VC on the resistance to core-to-skin heat transfer, i.e., tissue resistance (insulation) in the fully vasoconstricted state. Resistance to heat loss is a function of both physiological adjustments (VC) and characteristics of the passive system (e.g., muscle mass). Because a common sequelae of human aging is a progressive loss of muscle mass (sarcopenia), sarcopenic elderly men and women may be at even greater risk of hypothermia and hypothermia-related problems. Therefore, the proposed studies under Specific Aim 4 will include differences in muscle mass within age groups.
| Greaney, Jody L; Stanhewicz, Anna E; Proctor, David N et al. (2015) Impairments in central cardiovascular function contribute to attenuated reflex vasodilation in aged skin. J Appl Physiol (1985) 119:1411-20 |
| Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry (2015) Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms. Clin Sci (Lond) 129:159-67 |
| Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2015) Impaired increases in skin sympathetic nerve activity contribute to age-related decrements in reflex cutaneous vasoconstriction. J Physiol 593:2199-211 |
| Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry (2015) Sympathetic control of reflex cutaneous vasoconstriction in human aging. J Appl Physiol (1985) 119:771-82 |
| Kenney, W Larry; Stanhewicz, Anna E; Bruning, Rebecca S et al. (2014) Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation? Eur J Appl Physiol 114:467-79 |
| Stanhewicz, Anna E; Greaney, Jody L; Kenney, W Larry et al. (2014) Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating. Am J Physiol Regul Integr Comp Physiol 307:R914-9 |
| Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2014) Muscle sympathetic nerve activity during cold stress and isometric exercise in healthy older adults. J Appl Physiol (1985) 117:648-57 |
| Kenney, W Larry; Craighead, Daniel H; Alexander, Lacy M (2014) Heat waves, aging, and human cardiovascular health. Med Sci Sports Exerc 46:1891-9 |
| Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2014) Lack of limb or sex differences in the cutaneous vascular responses to exogenous norepinephrine. J Appl Physiol (1985) 117:1417-23 |
| Bruning, Rebecca S; Dahmus, Jessica D; Kenney, W Larry et al. (2013) Aspirin and clopidogrel alter core temperature and skin blood flow during heat stress. Med Sci Sports Exerc 45:674-82 |
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