Clinical Implications and Perspectives

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In conclusion, aging is associated with many skin microvasculature changes, all with a negative influence on tissue nutrition, which can explain the increased fragility and vulnerability of elderly skin to the different noxae and to the environment stress. Thermoregulatory adaptive mechanisms are also affected, resulting in a reduced capability to cope with both heat and cold stress.

Even without endeavoring to analyze the intricacy of the interactions between aging and modifiable risk factors for atherosclerosis, it is worth remembering that an age-altered vascular substrate increases susceptibility to the injury from modifiable risk factors. The presence of risk factors, in turn, may accelerate vascular aging.

The skin microcirculatory bed represents a window for estimating "biological age" as opposed to chronological age and a useful clinical model for noninvasive investigation of mechanisms involved in vascular senescence.


Aging: The natural and continuous process of becoming old. For medical purposes, at present the age at which a subject is elderly is set at 65 years.

Endothelium: Cell monolayer aligned along all the vascular tree, at the interface between bloodstream and vascular wall.

Flowmotion: Rhythmic oscillations of the blood flow in microvessels.

Skin perfusion: Blood flow supply to the skin.

Vasomotion: Rhythmic oscillations of the diameter of microvessels.


1. Lakatta, E. G. (2003). Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises. Part III: Cellular and molecular clues to heart and arterial aging. Circulation 107, 490-497. An updated overview of vascular biology of aging.

2. Benetos, A., Okuda, K., Khan, M. Y., Skurnick, J., Labat, C., Bean, K., and Aviv, A. (2001). Telomere length as an indicator of biological aging: The gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37, 381-385.

3. Minamino, T., Miyauchi, H., Yoshida, T., Ishida, Y., Yoshida, H., and Komuro, I. (2002). Endothelial cell senescence in human atherosclerosis: Role of telomere in endothelial dysfunction. Circulation 105, 1541-1544.

4. Rauscher, F. M., Goldschmidt-Clermont, P. J., Davis, B. H., Wang, T., Gregg, D., Ramaswami, P., Pippen, A. M., Annex, B. H., Dong, C., and Taylor, D. A. (2003). Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108, 457-463.

5. Sherr, C., and DePinho, R. (2001). Cellular senescence: Mitotic clock or culture shock? Cell Biol. 102, 407-410.

6. Holtz, J. (1996). Hemodynamics in regional circulatory beds and local vascular reactivity. In Comprehensive Human Physiology, R. Greger and U. Windhorst, eds., Vol. 2, pp. 1917-1939. Berlin: SpringerVerlag. Reference text for detailed information about physiology of regional microcirculatory beds.

7. Bertuglia, S., Colantuoni, A., Coppini, G., and Intaglietta, M. (1991). Hypoxia- or hyperoxia-induced changes in arteriolar vasomotion in skeletal muscle microcirculation. Am. J. Physiol. 260, H362-H372.

8. Bernardi, L., Hayoz, D., Wenzel, R., Passino, C., Calciati, A., Weber, R., and Noll, G. (1997). Synchronous and baroceptor-sensitive oscillations in skin microcirculation: Evidence for central autonomic control. Am. J. Physiol. 273, H1867-H1878.

9. Smith, L. (1989). Histopathologic characteristics and ultrastructure of aging skin. Cutis 43, 414-424.

10. Grove, G. (1989). L. Physiologic changes in older skin. Clin. Geriatr. Med. 5, 115-125.

11. Noon, J. P., Walker, B. R., Webb, D. J., Shore, A. C., Holton, D. W., Edwards, H. V., and Watt, G. C. (1997). Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J. Clin. Invest. 99, 1873-1879.

12. Antonios, T. F., Rattray, F. M., Singer, D. R., Markandu, N. D., Mortimer, P. S., and MacGregor, G. A. (2003). Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension. Heart 89, 175-178.

13. Ajami, R. S., and Rifkind, J. M. (1998). Hemorheological changes during human aging. Gerontology 44, 111-120.

14. Van den Brande, P., von Kemp, K., De Coninck, A., and Debing, E. (1997). Laser Doppler flux characteristics at the skin of the dorsum of the foot in young and in elderly healthy human subjects. Microvasc. Res. 53, 156-162. Clear summary of the differences in skin microvascular perfusion between elderly and young normal subjects.

15. Kellogg, D. L., Jr., Morris, S. R., Rodriguez, S. B., Liu, Y., Grossmann, M., Stagni, G., and Shepherd, A. M. (1998). Thermoregulatory reflexes and cutaneous active vasodilation during heat stress in hypertensive humans. J. Appl. Physiol. 85, 175-180.

16. Rossi, M., Cupisti, A., Mariani, S., Santoro, G., and Pentimone, F. (2002). Endothelium-dependent and endothelium-independent skin vasoreactivity in the elderly. Aging Clin. Exp. Res. 14, 343-346.

Further Reading

Chang, E., Yang, J., Nagavarapu, U., and Herron, G. S. (2002). Aging and survival of cutaneous microvasculature. J. Invest. Dermatol. 118, 752-758.

Pierzga, J. M., Frymoyer, A., and Kenney, W. L. (2003). Delayed distribution of active vasodilation and altered vascular conductance in aged skin. J. Appl. Physiol. 94, 1045-1053.

Capsule Biography

Marco Rossi, M.D., graduated in Medicine from the Medical School of Pisa University. His is a specialist in cardiovascular diseases and in internal medicine and a researcher at the University of Pisa, Department of Internal Medicine, with clinical and teaching activity at the same department. A Fellow of European Society of Microcirculation, he is a member of the National Committee of Italian Society of Clinical Hemorheology and Microcirculation and of Tuscan-Umbrian Section of the Italian Society of Angiology and Vascular Pathology, as well as of Working Groups on dia betic arteriopathy of the Italian Society of Angiology of Tuscan-Umbrian section and Vascular Pathology.

He is author of numerous full papers in peer-reviewed international Journals. His main research fields are represented by the study of peripheral microcirculation in aging and in subjects with peripheral arterial diseases and other pathological conditions and by the study of vascular disease and pathophysiology by ultrasound. He is author of numerous full papers in peer-reviewed international journals.

Carlo Palombo, M.D., graduated in Medicine from the Medical School of Pisa University. He is a specialist in cardiology and clinical pharmacology and an Associate Professor of Medicine at the University of Pisa, Department of Internal Medicine.

He is a Fellow of the European Society of Cardiology, and a member of the Italian Societies of Cardiology, Hypertension, Cardiovascular Research; European and International Societies of Hypertension; Working Group on Echocardiography of the European Society of Cardiology; and the Study Group on Arterial Mechanics of the Italian Society of Hypertension.

His clinical and teaching activity is at the Department of Internal Medicine, University of Pisa, and at the Institute of Clinical Physiology of the National Research Council, Pisa. He is author of more than 150 full papers, most of them in peer-reviewed international journals.

His main research fields are represented by the study of hypertensive heart disease; coronary and peripheral microcirculation in subjects with risk factors for atherosclerosis; arterial mechanics; vascular ultrasound; and cardiovascular aspects of insulin resistance.

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