Activatable senoprobes and senolytics: Novel strategies to detect and target senescent cells

Morsli, Samir; Doherty, Gary J.; Muñoz‐Espín, Daniel

doi:10.1016/j.mad.2021.111618

Cited by 29 publications

(18 citation statements)

References 217 publications

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“…Owing to its modifiable physiochemical properties, nanotechnology allows controlled delivery and release of various payloads to targeted cells, making it an enabling technology for detection, diagnosis, and drug delivery in cancer treatment. Many nanomaterials, particularly nanoparticles (NPs), have been tailor-made as nanocarriers to target SnCs for senescence detection and therapeutic interventions ( 108 ). The large surface area of NPs can be covalently modified with different functionalities such as peptides, antibodies, or nucleic acids.…”

Section: Strategies To Target Senescent Cells Therapeuticallymentioning

confidence: 99%

Cellular senescence: a key therapeutic target in aging and diseases

Zhang¹,

Pitcher²,

Yousefzadeh³

et al. 2022

Journal of Clinical Investigation

243

114

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Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease. Importantly, senotherapeutics have been developed to pharmacologically eliminate SnCs, termed senolytics, or suppress the SASP and other markers of senescence, termed senomorphics. Based on extensive preclinical studies as well as small clinical trials demonstrating the benefits of senotherapeutics, multiple clinical trials are under way. This Review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.

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Section: Strategies To Target Senescent Cells Therapeuticallymentioning

confidence: 99%

Cellular senescence: a key therapeutic target in aging and diseases

Zhang¹,

Pitcher²,

Yousefzadeh³

et al. 2022

Journal of Clinical Investigation

243

114

View full text Add to dashboard Cite

show abstract

“…Another interesting approach to study biological processes in vivo, including hematopoietic, senescence and leukemic pathways, is the use of two-photon microscopy [199][200][201][202]. This technique was useful for demonstrating that HSPC from aged mice, compared to those from younger animals, showed distinct relationships to BM architectural features, decreased adhesion to the stroma and a tendency to increase myelomonocytic differentiation when transplanted into younger mice hosts [199].…”

Section: In Vivo Rodent Modelsmentioning

confidence: 99%

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

Salazar-Terreros

Vernot

2022

IJMS

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Cellular senescence is recognized as a dynamic process in which cells evolve and adapt in a context dependent manner; consequently, senescent cells can exert both beneficial and deleterious effects on their surroundings. Specifically, senescent mesenchymal stromal cells (MSC) in the bone marrow (BM) have been linked to the generation of a supporting microenvironment that enhances malignant cell survival. However, the study of MSC’s senescence role in leukemia development has been straitened not only by the availability of suitable models that faithfully reflect the structural complexity and biological diversity of the events triggered in the BM, but also by the lack of a universal, standardized method to measure senescence. Despite these constraints, two- and three dimensional in vitro models have been continuously improved in terms of cell culture techniques, support materials and analysis methods; in addition, research on animal models tends to focus on the development of techniques that allow tracking leukemic and senescent cells in the living organism, as well as to modify the available mice strains to generate individuals that mimic human BM characteristics. Here, we present the main advances in leukemic niche modeling, discussing advantages and limitations of the different systems, focusing on the contribution of senescent MSC to leukemia progression.

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“…Several approaches to increase the specificity and safety profile of the senolytic small molecules identified, mainly based on the use of drug delivery approaches, are currently under development [ 154 ]. Based on the fact that most of the reported SnC types share an elevated activity of the lysosomal senescence-associated β-galactosidase activity (SA-β-gal), pro-drugs with a cleavable galactose moiety attached to a senolytic compound can lead to the specific release of the compound of interest in SnCs.…”

Section: Senotherapeutic Molecules In Preclinical Studies and Clinica...mentioning

confidence: 99%

New Trends in Aging Drug Discovery

et al. 2022

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Aging is considered the main risk factor for many chronic diseases that frequently appear at advanced ages. However, the inevitability of this process is being questioned by recent research that suggests that senescent cells have specific features that differentiate them from younger cells and that removal of these cells ameliorates senescent phenotype and associated diseases. This opens the door to the design of tailored therapeutic interventions aimed at reducing and delaying the impact of senescence in life, that is, extending healthspan and treating aging as another chronic disease. Although these ideas are still far from reaching the bedside, it is conceivable that they will revolutionize the way we understand aging in the next decades. In this review, we analyze the main and well-validated cellular pathways and targets related to senescence as well as their implication in aging-associated diseases. In addition, the most relevant small molecules with senotherapeutic potential, with a special emphasis on their mechanism of action, ongoing clinical trials, and potential limitations, are discussed. Finally, a brief overview of alternative strategies that go beyond the small molecule field, together with our perspectives for the future of the field, is provided.

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Activatable senoprobes and senolytics: Novel strategies to detect and target senescent cells

Cited by 29 publications

References 217 publications

Cellular senescence: a key therapeutic target in aging and diseases

Cellular senescence: a key therapeutic target in aging and diseases

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

New Trends in Aging Drug Discovery

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