Distinct secretomes in p16- and p21- positive senescent cells across tissues DOI Creative Commons
Dominik Saul, Diana Jurk, Madison L. Doolittle

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 5, 2023

SUMMARY Senescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21 Cip1 and p16 Ink4a have long served as markers cellular senescence. However, their individual roles remain incompletely elucidated. Thus, we conducted comprehensive examination multiple single-cell RNA sequencing (scRNA-seq) datasets spanning both murine human tissues during aging. Our analysis revealed that transcripts demonstrate significant heterogeneity across distinct cell types tissues, frequently exhibiting lack co-expression. Moreover, identified tissue-specific variations in SASP profiles linked to or expression. study underscores extraordinary diversity senescence SASP, emphasizing these phenomena are inherently cell- tissue-dependent. few factors consistently contribute shared “core” SASP. These findings highlight need for more nuanced investigation wide array biological contexts.

Language: Английский

Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions DOI Open Access
Merin Lawrence, Abhishek Goyal, Shelly Pathak

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7411 - 7411

Published: July 5, 2024

Advancing age is associated with several age-related diseases (ARDs), musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic contributing towards considerable number patients, a deeper understanding bone aging the need hour. One underlying factors cellular senescence and its secretory phenotype (SASP). SASP comprises pro-inflammatory markers, cytokines chemokines that arrest cell growth development. The accumulation over years leads to chronic low-grade inflammation advancing age, also known as inflammaging. pathways molecular mechanisms focused on inflammaging are currently limited but increasingly being explored. Most genes, involved in coincide those cancer other ARDs like osteoarthritis (OA). Thus, exploring these using techniques sequencing, identifying combatting them most suitable approach crucial for healthy early detection ARDs. Several approaches can be used aid regeneration reduce bone. These may pharmacological, non-pharmacological lifestyle interventions. increasing evidence intricate relationship between aging, senescence, ARDs, anti-aging strategies marrow (BM).

Language: Английский

Citations

6

Senescence as a therapeutic target in cancer and age-related diseases DOI
Domhnall McHugh, Imanol Durán, Jesús Gil

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 24(1), P. 57 - 71

Published: Nov. 15, 2024

Language: Английский

Citations

6

Role of Senescent Cells in Cutaneous Wound Healing DOI Creative Commons
Allison M. Andrade,

Mingda Sun,

Nathan Gasek

et al.

Biology, Journal Year: 2022, Volume and Issue: 11(12), P. 1731 - 1731

Published: Nov. 29, 2022

Cellular senescence has gained increasing attention in the field of aging research. Senescent cells have been implicated biological processes, tumorigenesis, development, and wound repair amongst other processes pathologies. Recent findings reveal that senescent can both promote inhibit cutaneous healing processes. Relating acute chronic wounds will help to clarify their role inform our understanding cell heterogeneity. To this apparent contradiction guide future research therapeutic we review rapidly growing cellular its biology.

Language: Английский

Citations

24

A p21‐GFP zebrafish model of senescence for rapid testing of senolytics in vivo DOI Creative Commons
Samir Morsli, Catarina M. Henriques,

Pamela S. Ellis

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)

Published: April 11, 2023

Senescence drives the onset and severity of multiple ageing-associated diseases frailty. As a result, there has been an increased interest in mechanistic studies search for compounds targeting senescent cells, known as senolytics. Mammalian models are commonly used to test senolytics generate functional toxicity data at level organs systems, yet this is expensive time consuming. Zebrafish share high homology genes associated with human ageing disease. They can be genetically modified relatively easily. In larvae, most develop within 5 days fertilisation transparent, which allows tracking fluorescent cells vivo real time, testing drug off-target assessment cellular phenotypic changes. Here, we have generated transgenic zebrafish line that expresses green protein (GFP) under promoter key senescence marker, p21. We show increase p21:GFP

Language: Английский

Citations

13

Distinct secretomes in p16- and p21- positive senescent cells across tissues DOI Creative Commons
Dominik Saul, Diana Jurk, Madison L. Doolittle

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 5, 2023

SUMMARY Senescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21 Cip1 and p16 Ink4a have long served as markers cellular senescence. However, their individual roles remain incompletely elucidated. Thus, we conducted comprehensive examination multiple single-cell RNA sequencing (scRNA-seq) datasets spanning both murine human tissues during aging. Our analysis revealed that transcripts demonstrate significant heterogeneity across distinct cell types tissues, frequently exhibiting lack co-expression. Moreover, identified tissue-specific variations in SASP profiles linked to or expression. study underscores extraordinary diversity senescence SASP, emphasizing these phenomena are inherently cell- tissue-dependent. few factors consistently contribute shared “core” SASP. These findings highlight need for more nuanced investigation wide array biological contexts.

Language: Английский

Citations

13