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Biochemistry (Moscow). Papers in Press. Published on April 29, 2019 as Manuscript BM18-334.

Defective Central Immune Tolerance Induced by High-Dose D-Galactose Resembles Aging

H. M. Du1,2,a, Y. J. Wang1,b, X. Liu1,c, S. L. Wang2,d, S. M. Wu3,e, Z. Yuan3,f, and X. K. Zhu1,g*

1Research Center, Shengjing Hospital of China Medical University, Economic Development Zone, 117000 Benxi, China

2Department of Oncology, Shengjing Hospital of China Medical University, 110022 Shenyang, China

3Department of Blood Transfusion, Shengjing Hospital of China Medical University, 110022 Shenyang, China

*To whom correspondence should be addressed.

Received December 4, 2018; Revised February 12, 2019; Accepted February 12, 2019
D-Galactose (D-Gal) promotes accumulation of reactive oxygen species and formation of advanced glycation end-products, ultimately resulting in oxidative stress. D-Gal has been widely used to induce accelerated aging in anti-aging medical research. Although thymic epithelial cells are particularly sensitive to oxidative stress, there are few reports on the thymus changes accompanying D-Gal-induced aging in mice. To study the effect of D-Gal on rodent thymus, we investigated the degree of thymus atrophy and changes in the atrophy relative index in C57BL/6J mice following subcutaneous injection of D-Gal at different doses (200, 500, 1000 mg/kg per day) for 60 days. Compared with the vehicle-treated (0.9% saline) and young controls, D-Gal at doses of 500 and 1000 mg/kg per day led to a significant thymic atrophy; the latter dose caused atrophy similar to that observed in naturally aged (18-20-month-old) mice. Mice treated with high-dose D-Gal exhibited greater immunosenescence, defective central immune tolerance, increased levels of activated splenic immune cell, and chronic low-grade inflammation, i.e., outcomes similar to those observed in natural aging in mice. Taken together, our results indicate that mice treated with high-dose D-Gal may be a valid model for studying induced thymic atrophy and effects of aging on the immune system.
KEY WORDS: D-galactose, oxidative stress, thymic aging, central immune tolerance, negative selection