Prof. L. Donehower’s main scientific theme is investigation on the role of tumor suppressors in cancer development and aging. The focus of L. Donehower’s researches is investigation of protective properties of p53 factor. In L. Donehower’s laboratory, mice having defective gene of p53 suppressor were created. Such mice have normal development, but since an early age, they have been demonstrating extremely high sensitivity to various forms of cancer. Similar phenotype is typical for «super» mice with additional copies of p53 or ARF genes, and for mice with genetically suppressed MDM2 activity. «Super» mouse with additional p53 and ARF genes has increased resistance to cancers and long life span. However, the situation is absolutely different when normal regulation of p53 gene is disturbed. Loss of p53 regulation was reached by removing N-end domain of the protein responsible for the interaction with MDM2. So, «m» mouse has a deletion 500 kilobase long that results in 26 genes following p53 removed and 6 exons of p53 gene removed as well. Another example is Р44tg mouse that expresses shortened form of p53 (p44). Both mouse models have increased stability and transcriptional activity of p53. That leads to increased cancer resistance but hastens aging of the animals due to depletion of the regenerative functions of their tissues. Similar phenotype is typical for mice with defective BRCA1 gene (maintenance factor of genome stability) or with defective ZMPTE24 protease. Such mice are exposed to permanent stress at the cellular level because of persisting DNA damages and chromosomal instability. At present, researches seeking for molecular mechanisms of influence of p53 on aging are conducted in L. Donehower’s laboratory. The basis for those researches are developed mouse models which have mutant p53. When p53 activity is heightened while basic regulation is kept, p53 protects from cancer but does not slow aging down. Completely lost p53 highly predisposes to cancer. A mouse with hyperexpression of p53 (р53 +/m) has much higher cancer resistance but shortened life span.