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Figure 1. Interaction between genetic factors, estrogen and aging in the development of Th1/TH2 differentiation and subsequent autoimmune diseases in aging women. DC: Dendritic cell; Th: T-helper cell.
(Figure omitted. See article PDF.)
Life expectancy in human beings has increased dramatically in the last century [1] and is expected to continue to increase, reaching 100 years in the USA and other industrialized countries by approximately 2040 [2]. In the USA, life expectancy has increased 10% since 1970 from an average of 70.8 years to an average of 78.3 years [3]. Women, on average, currently live nearly 3 years longer than men [2].
The dramatic gains in life expectancy achieved have allowed for concomitant gains in an understanding of immune system aging, termed immunosenescence. Recent analyses of immune system aging have revealed that individual longevity is closely tied to the preservation of healthy immune function [4].
The immunosenescence that occurs as humans age is therefore of increasing interest in medicine and deserving of research effort as life expectancy, particularly in developed countries, is increasing at a more rapid rate than concomitant improvements in meeting the medical needs of the elderly [5]. This is particularly true in women, who at current life expectancies will spend more than a third of their lifetimes in menopause.
Menopause, a period of time defined by the cessation of menstruation, is an experience common to all aging females. Cessation of menses results from a gradual deterioration in ovarian function, with declining production of follicles and falling levels of numerous endogenous hormones. Estrogen produced in postmenopausal females, furthermore, is of a different form than the one that is predominant during the reproductive years. Levels of the ovarian-derived 17b estradiol (E2), as ovarian follicles cease production, plunge as menopause nears, and estrogen in the form of estrone (E1) becomes the predominant form. E1 is produced by secretion of androstenedione by the ovarian stroma and the adrenal gland and is aromatized to E1 in the peripheral circulation. Conversion to E1 occurs primarily in adipose tissue, but also in muscle, liver, bone, bone marrow, fibroblasts and hair roots [201]. Postmenopausal deficits in estrogen and progesterone, and the replacement of E2, the primary estrogen of the reproductive years, to E1 carry impact far beyond the immune system.