Professor Vassilis Gorgoulis and colleagues published on December 27th in the highly prestigious scientific journal Nature Aging, a pioneering study related to the development of a pharmaceutical platform for selective elimination of senescent cells.

Cellular senescence is a stress response mechanism that is beneficial on a transient basis. However, persistence of senescent cells has been shown to play a role in a variety of age-related pathologies such as cancer, cardiovascular, neurodegenerative and autoimmune diseases. Thus, their elimination is anticipated to facilitate treatment of such pathological entities. Senolytics comprise mainly a class of anticancer drugs that were repurposed for the elimination of senescent cells (senolysis). Their main disadvantage is their toxicity and serious side effects, following their systemic administration, which renders them incompatible for senolysis in humans.

In the current work, Professor Gorgoulis and colleagues developed the innovative mGL392 senolytic platform, by encapsulating the newly synthesized GL392 reagent into a micelle nanocarrier. GL392 consists of a lipofuscin-binding domain scaffold specifically recognizing and interacting with lipofuscin -the dark matter- of senescent cells, conjugated with a senolytic agent (Dasatinib). This platform is accompanied by unique advantages allowing selective release and activity of the senolytic drug exclusively within senescent cells. By applying the platform in established cellular and animal senescence models, robust elimination of senescent cells was evident with no systemic toxicity. This platform developed by Professor Gorgoulis and collaborators opens new horizons towards targeted treatment of age-related diseases and alleviation of aging effects in humans.

pubmed

Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog.
Magkouta S, Veroutis D, Papaspyropoulos A, Georgiou M, Lougiakis N, Pippa N, Havaki S, Palaiologou A, Thanos DF, Kambas K, Lagopati N, Boukos N, Pouli N, Marakos P, Kotsinas A, Thanos D, Evangelou K, Sampaziotis F, Tamvakopoulos C, Pispas S, Petty R, Kotopoulos N, Gorgoulis VG. Nat Aging. 2024 Dec 27. doi: 10.1038/s43587-024-00747-4. Online ahead of print. PMID: 39730824