Aging is associated with degenerative diseases, and may result in a heavy medical burden for the society.Understanding the aging mechanism would provide an opportunity for developing a better treatment for aging-related diseases.Chronic administration of D-galactose in rodents induces physiological and behavioral changes that resemble natural aging.Another promising model to study aging processes is OXYS rat strain with genetically defined accelerated senescence developed in the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia).OXYS rats show an early development of age-associated pathological phenotypes similar to several geriatric disorders (Rumyantseva et al.,2008;Markovets et al., 2011).The behavioral alterations manifested by OXYS rats at the age of about 3 months were accompanied by MRI signs of neurodegeneration which progressed with age (Kolosova et al., 2011).Antioxidant supplementation was able to reduce some indices of accelerated senescence in OXYS rats (Kolosova et al., 2006, 2009;Stefanova et al., 2010, 2011).Diosgenin, one of the important bio-active ingredients in a Chinese medicine, dioscorea, has long been used as a precursor in manufactory for producing steroid hormones.In addition, diosgenin shows anti-oxidant activity, and improves spatial memory in senescent mice induced by D-galactose, suggesting that diosgenin may have beneficial effects on aging animals.In the present study we compared the behavioral and biochemical alterations in D-galactose-induced aging Wistar rats with that in OXYS rats and examined the protective effects of the natural-derived antioxidant diosgenin on these aging models.12-week-old male Wistar rats received daily treatment with D-galactose (0 or 150 mg/kg/day, i.p.) for 2 months.Certain groups of OXYS and D-galactose-treated Wistar rats received diosgenin orally (10 or 50 mg/kg/day) for 8 weeks.Compared to Wistar rats chronically treated with D-galactose, OXYS rats are a superior aging model because they showed typical behavioral deficits seen in old individuals (impaired working memory and object recognition, decreased sexual motivation).Diosgenin was found to improve some parameters of reproductive function in aging animals.