Abstract: The present disclosure is concerned with TDZD analogs for the treatment of various neurodegenerative diseases such as sarcopenia, supranuclear palsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, and dementia, and various cancers such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanomas, gliomas, leukemias, lymphomas, chronic myeloproliferative disorders, myelodysplastic syndromes, myeloproliferative neoplasms, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The disclosure provides a method of preventing or reducing protein aggregates using combretastatin-A4 (CA4) or an analog thereof. The disclosure also provides methods of reducing the risk, delaying the onset, delaying or slowing the progression, or reversing the signs or symptoms of a neurodegenerative (or other age-progressive) disease using a combretastatin-A4 (CA4) or an analog thereof. The combretastatin-A4 (CA4) or an analog thereof may bind glial fibrillary acidic protein (GFAP). The combretastatin-A4 (CA4) or an analog thereof is described by compounds of Formula (I).

Abstract: The present invention provides methods for identifying agents that increase lifespan and increase resistance to oxidative and/or electrophilic stress. Also provided are methods for identifying biomarkers of longevity or identifying pathways governing longevity in response to phosphatidylinositol 3,4,5-triphosphate signaling.