Age-related thymic atrophy in the guinea pig Laura P. Hale a, * , Amy G. Clark a , Jie Li a , Paula K. Greer a , Virginia Byers Kraus a,b a Department of Pathology, Duke University Medical Center, Durham, NC, 27710, USA b Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA Received 6 October 2000; received in revised form 5 December 2000; accepted 11 December 2000 Abstract We have characterized age-related thymic atrophy in the guinea pig, including identi®cation of antibodies that allow immunohistochemical assessment of thymopoiesis. Age-related thymic atrophy in guinea pigs more closely resembles what occurs in humans histologically and in thymus weight, cellularity, and percent functional area than do other rodent models. The guinea pig model is thus particularly well-suited to study the role of the thymic perivascular space in age-related thymic atrophy. We next tested the hypothesis that dietary supplementation with Vitamin C could prevent or delay age-related thymic atrophy. Thymus histology, weight, cellularity, and percent functional area did not differ at 12 months between groups that received 3, 30, or 150 mg Vitamin C daily from 4 months of age. Thus long-term supplementation with up to 130 mg/kg/day Vitamin C is insuf®cient to in¯uence the time course and extent of age-related thymic atrophy in guinea pigs. q 2001 Elsevier Science Ltd. All rights reserved. Keywords: Guinea pig; Thymus; Ascorbic acid; Aging; Immune function; Perivascular space; Immunohistochemistry T lymphocytes are the central regulatory and effec- tor cells of the immune system. T cells develop within the thymus, which thus plays a critical role in the initial development of immune system function [1]. In humans, the thymus attains its maximum size in the ®rst year of life. However unlike most organs, involu- tion of the thymus begins soon after birth and progresses with age [2,3]. Thymectomized adults do not demonstrate gross abnormalities in immune func- tion under normal conditions, which has been explained by the presence and longevity of post- thymic peripheral T cells. However, the ability of the thymus to generate new T cells becomes espe- cially important when the peripheral pool of T cells is depleted, such as in HIV infection or during high- dose chemotherapy for malignancy [4]. Regeneration of the T cell pool from peripheral T cells in the absence of thymopoiesis is incomplete and may lead to perpetuation of `holes' in the T cell repertoire or to an inability to generate immune responses to novel antigens [5]. The ability to respond to novel antigens is critical to maintain immune responses throughout adult life. Decreased thymic function has been hypothesized to account for the increased incidence of serious infections seen in elderly humans. Lack of thymic selection processes can also potentially lead to development of increased numbers of autoreactive T cells and clinically signi®cant autoimmune disease. The functional status of the thymus may thus play an important role in overall immune function and may in¯uence the potential risk for illness that is associated with aging. Developmental and Comparative Immunology 25 (2001) 509±518 0145-305X/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0145-305X(00)00071-9 www.elsevier.com/locate/devcompimm * Corresponding author. Tel.: 11-919-684-4771; fax: 11-919- 684-8756. E-mail address: laura.hale@duke.edu (L.P. Hale).