Scientific Approaches against Longevity and Directions to the Clinic
Increasing chronological age is the greatest risk factor for human diseases. Several pharmacological, dietary and genetic interventions that target aging and age-related diseases are known, but the general principles of these interventions remain unclear. Since aging is an extremely complex and multifactorial process, the transcriptome of well-known longevity interventions is analyzed to characterize common perturbations in gene expressions. The detection of common longevity signatures allows predicting new longevity compounds by drug repurposing which is superior to traditional drug discovery in terms of time and budget. As a result of this analysis, it is found that the target molecules with the highest scores include a variety of molecules including antioxidants, hypertension drugs and mTOR inhibitors (1). Experimental validation of the predicted compounds is provided by senescent human fibroblast and human progeroid cells with an accelerated aging disease. The potential effect of these candidate drugs on cellular senescence are being tested as senotherapeutic drugs have been already involved in clinical studies. In addition, omics studies are also being carried out in alternative tools such as long-lived mole-rat to determine the further mechanisms of aging and to utilize their regenerative capacities (2). As a result, our studies focus on perturbations targeting aging and age-related pathologies that could be translated into clinics by further studies.
1-Tyshkovskiy A, Bozaykut P, Borodinova AA, Gerashchenko MV, Ables GP, Garratt M, Khaitovich P, Clish CB, Miller RA, Gladyshev VN. Identification and Application of Gene Expression Signatures Associated with Lifespan Extension. Cell Metabolism, (2019); 30(3): 573-593.
2-Inci N, Akyildiz EO, Bulbul A, Turanli ET, Akgul E, Baykal AT, Colak F, Bozaykut P. JAK signaling and inflammatory phenotype during cellular senescence in blind mole rats: the reflection of being long-lived and cancer-resistant