Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan

Matteini, Francesca; Montserrat‐Vazquez, Sara; Florian, M. Carolina

doi:10.1002/1873-3468.14865

Cited by 3 publications

References 100 publications

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Repurposing the plant-derived compound apigenin for senomorphic effect in antiaging pipelines

Zhang,

Xu,

Jiang

et al. 2024

Preprint

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Cellular senescence is a cell fate triggered by inherent or environmental stress and characterized by stable cell cycle arrest accompanied by a hypersecretory feature, termed as the senescence-associated secretory phenotype (SASP). Senescent cell burden increases with natural aging, functionally contributing to age-related organ dysfunction and multiple disorders. In this study, we performed a large scale screening of a natural product library for senotherapeutic candidates by assessing their effects on human senescent cells. Apigenin, a dietary flavonoid previously reported with antioxidant and anti-inflammatory activities, exhibited a prominent capacity in targeting senescent cells as a senomorphic agent. In senescent cells, apigenin blocks the interactions between ATM/p38 and HSPA8, thus preventing transition of the acute stress-associated phenotype (ASAP) towards the SASP. Mechanistically, apigenin targets peroxiredoxin 6 (PRDX6), an intracellular redox-active molecule, suppressing the iPLA2 activity of PRDX6 and disrupting downstream reactions underlying the SASP development. Without reversing cellular senescence, apigenin deprives cancer cells of malignancy acquired from senescent stromal cells in culture, while reducing chemoresistance upon combination with chemotherapy in anticancer regimens. In preclinical trials, apigenin administration improves physical function of animals prematurely aged after whole body irradiation, alleviating physical frailty and cognitive impairment. Overall, our study demonstrates the potential of exploiting a naturally derived compound with senomorphic capacity to achieve geroprotective effects by modulating the SASP, thus providing a research platform for future exploration of novel natural agents against age-related conditions.

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Repurposing the plant-derived compound apigenin for senomorphic effect in antiaging pipelines

Zhang,

Xu,

Jiang

et al. 2024

Preprint

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Cell autocloning as a pathway to their real rejuvenation

Salnikov

2024

Front. Aging

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The article gives a brief description of geroprotection and rejuvenation methods known to date, presenting their main mechanisms and limitations. To overcome the main limitations of the process of rejuvenation, it is possible to use a process called “cell autocloning.” The principle of the proposed method of rejuvenation is as follows: a periodic process of autocloning of the cell nucleus is initiated in the cellular genome with the formation of one unstable daughter copy and its subsequent self-elimination. In this case, the process of cell division stops in the phase of nuclei divergence without subsequent physical separation of the cell itself. This is especially important for postmitotic cells, where the looping of the “unidirectional” line of the ontogenesis program into a “ring” will mean their transition into renewable cells. The prototype for autocloning mechanisms could be the already known ways in which cells adapt to the increasing amount of their damage over time. These are polyploidy and asymmetric cell division, relying on which it is possible to obtain a renewable process of cell nuclei division, when only the original nucleus remains as a result of division. Although this is not a simple task, there are possible pathways to its solution using approaches that can suggest modern knowledge from the field of molecular and cell biology and genetics. The realization of such a goal will require a lot of work, but the expected result justifies it.

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From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications

Saliev,

Singh

2024

Cells

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Cellular rejuvenation therapies represent a transformative frontier in addressing age-related decline and extending human health span. By targeting fundamental hallmarks of aging—such as genomic instability, epigenetic alterations, mitochondrial dysfunction, and cellular senescence—these therapies aim to restore youthful functionality to cells and tissues, offering new hope for treating degenerative diseases. Recent advancements have showcased a range of strategies, including epigenetic reprogramming, senolytic interventions, mitochondrial restoration, stem cell-based approaches, and gene-editing technologies like CRISPR. Each modality has demonstrated substantial potential in preclinical models and is now being cautiously explored in early-stage clinical trials. However, translating these therapies from the laboratory to clinical practice presents unique challenges: safety concerns, delivery precision, complex regulatory requirements, ethical considerations, and high costs impede widespread adoption. This review examines the current landscape of cellular rejuvenation, highlighting key advancements, potential risks, and the strategies needed to overcome these hurdles.

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Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan

Cited by 3 publications

References 100 publications

Repurposing the plant-derived compound apigenin for senomorphic effect in antiaging pipelines

Repurposing the plant-derived compound apigenin for senomorphic effect in antiaging pipelines

Cell autocloning as a pathway to their real rejuvenation

From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications

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