bims-caglex 2024-06-09 papers

Tissue Eng Part C Methods. 2024 Jun 06.

Young TSPC-derived exosomal circPVT1 ameliorates aging-impaired cell function via SIRT1/NF-κB.

Weifeng Han, Dongqiang Gu, Xiaoya Li, Hongguang Chen, Xu Tao, Lei Chen.

Tendon stem/progenitor cell (TSPC) senescence is often associated with age-dependent tendon diseases and greatly reduces the capacities for tendon repair and replacement. Exosomes contain bioactive molecules and have been increasingly used in regenerative medicine. In the present study, we demonstrated the anti-aging effects of young exosomes from circPVT1-overexpressing TSPCs at early passages (circPVT1-exo). These exosomes attenuated the phenotypes of aged TPSCs at late passages (L-TSPCs) by enhancing self-renewal and proliferation abilities and suppressing cell senescence, maintain their tenogenic capacity, and weaken their osteogenic differentiation. Mechanistically, circPVT1-exo inhibited the NF-κB pathway and increased SIRT1 expression in L-TSPCs. Knockdown of SIRT1 reversed these effects as evidenced by increased senescence, decreased proliferation, and tenogenic differentiation. These results suggest that circPVT1-exo may ameliorate aging-impaired TSPC function by modulating the SIRT1/NF-κB pathway, suggesting that circPVT1-exo has therapeutic potential for age-related diseases.

DOI: https://doi.org/10.1089/ten.TEC.2024.0057

Inflamm Regen. 2024 Jun 03. 44(1): 28

Role of cellular senescence in inflammation and regeneration.

Yuki Saito, Sena Yamamoto, Takako S Chikenji.

Cellular senescence is the state in which cells undergo irreversible cell cycle arrest and acquire diverse phenotypes. It has been linked to chronic inflammation and fibrosis in various organs as well as to individual aging. Therefore, eliminating senescent cells has emerged as a potential target for extending healthy lifespans. Cellular senescence plays a beneficial role in many biological processes, including embryonic development, wound healing, and tissue regeneration, which is mediated by the activation of stem cells. Therefore, a comprehensive understanding of cellular senescence, including both its beneficial and detrimental effects, is critical for developing safe and effective treatment strategies to target senescent cells. This review provides an overview of the biological and pathological roles of cellular senescence, with a particular focus on its beneficial or detrimental functions among its various roles.

Keywords: Aging; Cell cycle arrest; Cellular senescence; Fibrosis; Senescence-associated secretory phenotype (SASP); Tissue remodeling

DOI: https://doi.org/10.1186/s41232-024-00342-5

Microbiome Res Rep. 2024 ;3(2): 13

Gut microbiota: an ideal biomarker and intervention strategy for aging.

Xuan Xu, Tangchang Xu, Jing Wei, Tingtao Chen.

Population aging is a substantial challenge for the global sanitation framework. Unhealthy aging tends to be accompanied by chronic diseases such as cardiovascular disease, diabetes, and cancer, which undermine the welfare of the elderly. Based on the fact that aging is inevitable but retarding aging is attainable, flexible aging characterization and efficient anti-aging become imperative for healthy aging. The gut microbiome, as the most dynamic component interacting with the organism, can affect the aging process through its own structure and metabolites, thus holding the potential to become both an ideal aging-related biomarker and an intervention strategy. This review summarizes the value of applying gut microbiota as aging-related microbial biomarkers in diagnosing aging state and monitoring the effect of anti-aging interventions, ultimately pointing to the future prospects of microbial intervention strategies in maintaining healthy aging.

Keywords: Aging; anti-aging intervention; gut microbiota; microbial biomarker

DOI: https://doi.org/10.20517/mrr.2023.68

bioRxiv. 2024 May 26. pii: 2024.05.23.595605. [Epub ahead of print]

Senescent-like microglia limit remyelination through the senescence associated secretory phenotype.

Phillip S Gross, Violeta Duran Laforet, Zeeba Manavi, Sameera Zia, Sung Hyun Lee, Nataliia Shults, Sean Selva, Enrique Alvarez, Jason R Plemel, Dorothy P Schafer, Jeffrey K Huang.

The capacity to regenerate myelin in the central nervous system (CNS) diminishes with age. This decline is particularly evident in multiple sclerosis (MS), which has been suggested to exhibit features of accelerated biological aging. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells (SCs) accumulate within demyelinated lesions after injury, and their elimination enhances remyelination in young mice but not in aged mice. In young mice, we observed the upregulation of senescence-associated transcripts primarily in microglia after demyelination, followed by their reduction during remyelination. However, in aged mice, senescence-associated factors persisted within lesions, correlating with inefficient remyelination. We found that SC elimination enhanced remyelination in young mice but was ineffective in aged mice. Proteomic analysis of senescence-associated secretory phenotype (SASP) revealed elevated levels of CCL11/Eotaxin-1 in lesions, which was found to inhibit efficient oligodendrocyte maturation. These results suggest therapeutic targeting of SASP components, such as CCL11, may improve remyelination in aging and MS.

DOI: https://doi.org/10.1101/2024.05.23.595605

Life Sci Alliance. 2024 Aug;pii: e202302503. [Epub ahead of print]7(8):

STAT3 inhibition recovers regeneration of aged muscles by restoring autophagy in muscle stem cells.

Giorgia Catarinella, Andrea Bracaglia, Emilia Skafida, Paola Procopio, Veronica Ruggieri, Cristina Parisi, Marco De Bardi, Giovanna Borsellino, Luca Madaro, Pier Lorenzo Puri, Alessandra Sacco, Lucia Latella.

Age-related reduction in muscle stem cell (MuSC) regenerative capacity is associated with cell-autonomous and non-cell-autonomous changes caused by alterations in systemic and skeletal muscle environments, ultimately leading to a decline in MuSC number and function. Previous studies demonstrated that STAT3 plays a key role in driving MuSC expansion and differentiation after injury-activated regeneration, by regulating autophagy in activated MuSCs. However, autophagy gradually declines in MuSCs during lifespan and contributes to the impairment of MuSC-mediated regeneration of aged muscles. Here, we show that STAT3 inhibition restores the autophagic process in aged MuSCs, thereby recovering MuSC ability to promote muscle regeneration in geriatric mice. We show that STAT3 inhibition could activate autophagy at the nuclear level, by promoting transcription of autophagy-related genes, and at the cytoplasmic level, by targeting STAT3/PKR phosphorylation of eIF2α. These results point to STAT3 inhibition as a potential intervention to reverse the age-related autophagic block that impairs MuSC ability to regenerate aged muscles. They also reveal that STAT3 regulates MuSC function by both transcription-dependent and transcription-independent regulation of autophagy.

DOI: https://doi.org/10.26508/lsa.202302503