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

---

H. M. Du^1,2,a, Y. J. Wang^1,b, X. Liu^1,c, S. L. Wang^2,d, S. M. Wu^3,e, Z. Yuan^3,f, and X. K. Zhu^1,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

DOI: 10.1134/S000629791906004X

---