bims-caglex 2024-05-05 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2024–05–05
eleven papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: JACC Family Series.
Ohwia caudata aqueous extract attenuates senescence in aging adipose-derived mesenchymal stem cells.
NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention.
The effect of T cell aging on the change of human tissue structure.
Astaxanthin attenuates UV-irradiation aging process via activating JNK-1/DAF-16 in Caenorhabditis elegans.
Nanocarriers for natural polyphenol senotherapeutics.
SYNTHESIS OF NEW BODIPY HYDRAZIDE FLUORESCENT PROBES FOR THE DETECTION OF CARBONYLATED PROTEINS GENERATED BY OXIDATIVE STRESS.
Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration.
Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.
Exploring the roles of non-coding RNAs in liver regeneration.
Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies.

JACC Basic Transl Sci. 2024 Apr;9(4): 522-534

Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: JACC Family Series.

Manish Kumar, Pengyi Yan, George A Kuchel, Ming Xu.

  The prevalence of cardiovascular diseases markedly rises with age. Cellular senescence, a hallmark of aging, is characterized by irreversible cell cycle arrest and the manifestation of a senescence-associated secretory phenotype, which has emerged as a significant contributor to aging, mortality, and a spectrum of chronic ailments. An increasing body of preclinical and clinical research has established connections between senescence, senescence-associated secretory phenotype, and age-related cardiac and vascular pathologies. This review comprehensively outlines studies delving into the detrimental impact of senescence on various cardiovascular diseases, encompassing systemic atherosclerosis (including coronary artery disease, stroke, and peripheral arterial disease), as well as conditions such as hypertension, congestive heart failure, arrhythmias, and valvular heart diseases. In addition, we have preclinical studies demonstrating the beneficial effects of senolytics-a class of drugs designed to eliminate senescent cells selectively across diverse cardiovascular disease scenarios. Finally, we address knowledge gaps on the influence of senescence on cardiovascular systems and discuss the future trajectory of strategies targeting senescence for cardiovascular diseases.

Keywords:  biological aging; cardiovascular disease; geriatric cardiology; senescent cells; senolytics

DOI:  https://doi.org/10.1016/j.jacbts.2023.12.003
Heliyon. 2024 May 15. 10(9): e29729

Ohwia caudata aqueous extract attenuates senescence in aging adipose-derived mesenchymal stem cells.

Tsung-Jung Ho, Bruce Chi-Kang Tsai, Goswami Debakshee, Marthandam Asokan Shibu, Chia-Hua Kuo, Chih-Hsueh Lin, Pi-Yu Lin, Shinn-Zong Lin, Wei-Wen Kuo, Chih-Yang Huang.

  Stem cells exhibit pluripotency and self-renewal abilities. Adipose-derived mesenchymal stem cells can potentially be used to reconstruct various tissues. They possess significant versatility and alleviate various aging-related diseases. Unfortunately, aging leads to senescence, apoptosis, and a decline in regenerative capacity in adipose-derived mesenchymal stem cells. These changes necessitate a strategy to mitigate the effects of aging on stem cells. Ohwia caudata (O. caudata) has therapeutic effects against several illnesses. However, studies on whether O. caudata has therapeutic effects against aging are lacking. In this study, we aimed to identify potential therapeutic anti-aging effects in the crude aqueous extract of O. caudata on adipose-derived mesenchymal stem cells. Using 0.1 μM doxorubicin, we induced aging in human adipose-derived mesenchymal stem cells (hADMSCs) and evaluated whether various concentrations of O. caudata aqueous extract exhibit anti-aging effects on them. The O. caudata extract exhibited significant antioxidant effects on hADMSCs without any toxicity. Furthermore, after treatment with the O. caudata aqueous extract, the levels of mitochondrial superoxide, DNA double-strand breaks, and telomere shortening were reduced in the hADMSCs subjected to doxorubicin-induced aging. The extract also suppressed doxorubicin-induced aging by upregulating klotho and downregulating p21 in hADMSCs. These ﬁndings indicated that the O. caudata extract exhibited anti-aging properties that modulated hADMSC homeostasis. Therefore, it could be a potential candidate for restoring the self-renewal ability and multipotency of aging hADMSCs.

Keywords:  Adipose-derived mesenchymal stem cells; Desmodium caudatum; Herbal medicine; Ohwia caudata; Pluripotency; Self-renewal

DOI:  https://doi.org/10.1016/j.heliyon.2024.e29729
Front Pharmacol. 2024 ;15 1368835

NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention.

Ping Ding, Yuanming Song, Yang Yang, Cheng Zeng.

  NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 inflammasome leads to the production of pro-inflammatory cellular contents, such as interleukin (IL)-1β and IL-18, and induction of inflammatory cell death known as pyroptosis, thereby amplifying or sustaining inflammation. While a balanced inflammatory response is beneficial for resolving damage and promoting tissue healing, excessive activation of the NLRP3 inflammasome and pyroptosis can have harmful effects. The involvement of the NLRP3 inflammasome has been observed in various cardiovascular diseases (CVD). Indeed, the NLRP3 inflammasome and its associated pyroptosis are closely linked to key cardiovascular risk factors including hyperlipidemia, diabetes, hypertension, obesity, and hyperhomocysteinemia. Exercise compared with medicine is a highly effective measure for both preventing and treating CVD. Interestingly, emerging evidence suggests that exercise improves CVD and inhibits the activity of NLRP3 inflammasome and pyroptosis. In this review, the activation mechanisms of the NLRP3 inflammasome and its pathogenic role in CVD are critically discussed. Importantly, the purpose is to emphasize the crucial role of exercise in managing CVD by suppressing NLRP3 inflammasome activity and proposes it as the foundation for developing novel treatment strategies.

Keywords:  NLRP3 inflammasome; cardiovascular disease; exercise; intervation; pyroptosis

DOI:  https://doi.org/10.3389/fphar.2024.1368835
Immun Ageing. 2024 Apr 30. 21(1): 26

The effect of T cell aging on the change of human tissue structure.

Ling-Ling Xu, Xiang Chen, Jing-Ping Cheng.

  The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.

Keywords:  Aging; Blood vessels; Immune aging; Intestinal flora; Skeletal muscle; T cell aging

DOI:  https://doi.org/10.1186/s12979-024-00433-4
Photochem Photobiol. 2024 May 02.

Astaxanthin attenuates UV-irradiation aging process via activating JNK-1/DAF-16 in Caenorhabditis elegans.

Xiuping Lin, Chang-Sheng Shao, Shereen M Elsherbiny, Qing Huang.

  Astaxanthin (AST) is a xanthophyll carotenoid with strong oxidation resistance, which can effectively scavenge various free radicals and protect organisms from oxidative damage. AST is also known to have prominent anti-aging effects, but the underlying mechanism of AST in anti-radiation aging is largely unknown. In this work, we applied ultraviolet (UV) irradiation to accelerate the aging of Caenorhabditis elegans (C. elegans) and treated the nematodes with AST to explore whether and how AST could attenuate the radiation-induced aging effect. Our results showed that AST improved the survival rate of C. elegans, reduced the aging biomarkers, and alleviated the mitochondrial dysfunction caused by the irradiation. Based on the transcriptome sequencing analysis, we identified that the key genes regulated by AST were involved in JNK-MAPK and DAF-16 longevity signaling pathways. Furthermore, we employed jnk-1 and daf-16 mutants and verified the role of the JNK-1/DAF-16 signaling pathway in the anti-aging effect. As such, this study has not only demonstrated that AST can resist the aging process caused by UV-irradiation but also revealed the anti-aging mechanism of AST through JNK-1/DAF-16 activation in C. elegans.

Keywords:   Caenorhabditis elegans ; UV radiation; aging; astaxanthin; photoprotection

DOI:  https://doi.org/10.1111/php.13958
Aging Cell. 2024 Apr 29. e14178

Nanocarriers for natural polyphenol senotherapeutics.

Natali Joma, Patrick-Brian Bielawski, Anjali Saini, Ashok Kakkar, Dusica Maysinger.

  Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context-dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites. To address these limitations, nanocarriers such as polymer nanoparticles and lipid vesicles can be utilized to enhance the efficacy of senolytic polyphenols. Focusing on widely studied senolytic agents-specifically fisetin, quercetin, and resveratrol-we provide concise summaries of their physical and chemical properties, along with an overview of preclinical and clinical findings. We also highlight common signaling pathways and potential toxicities associated with these agents. Addressing challenges linked to nanocarriers, we present examples of senotherapeutic delivery to various cell types, both with and without nanocarriers. Finally, continued research and development of senolytic agents and nanocarriers are encouraged to reduce the undesirable effects of senescence on different cell types and organs. This review underscores the need for establishing reliable sets of senescence biomarkers that could assist in evaluating the effectiveness of current and future senotherapeutic candidates and nanocarriers.

Keywords:  cellular senescence; drug delivery; fisetin; nanocarriers; polyphenols; quercetin; resveratrol; senolytics; senomorphics

DOI:  https://doi.org/10.1111/acel.14178
Chembiochem. 2024 May 02. e202400093

SYNTHESIS OF NEW BODIPY HYDRAZIDE FLUORESCENT PROBES FOR THE DETECTION OF CARBONYLATED PROTEINS GENERATED BY OXIDATIVE STRESS.

Anthony Nina Diogo, Janek Hyzewicz, Marie-Paule Hamon, Jeremy Forté, Serge Thorimbert, Bertrand Friguet, Candice Botuha.

  Oxidative stress is a cellular disorder implicated in various severe diseases and redox biology and represents an important field of research for the last decades. One of the major consequences of oxidative stress is the carbonylation of proteins, which is also a reliable marker to assess protein oxidative modifications. Accumulation of carbonylated proteins has been associated with aging and age-related diseases and can ultimately causes cell death. Detection of these oxidative modifications is essential to understand and discover new treatments against oxidative stress. We describe the design and the synthetic pathway of new BODIPY fluorescent probes functionalized with hydrazide function for protein carbonyl labeling to improve existing methodologies such as 2D-Oxi electrophoresis. Hydrazide BODIPY analogues show very good fluorescent properties such as NIR emission up to 633 nm and quantum yield up to 0.88. These new probes were validated for the detection and quantification of carbonylated proteins with 2D-Oxi electrophoresis using mouse muscle protein extracts, as well as both flow cytometry and microscopy using oxidant stressed C2C12 cells.

Keywords:  carbonylated proteins * BODIPY* fluorescent probes * 2D-Oxi electrophoresis * flow cytometry *

DOI:  https://doi.org/10.1002/cbic.202400093
J Nanobiotechnology. 2024 May 03. 22(1): 219

Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration.

Yunzi Chen, Ye Li, Bin Li, Delin Hu, Ziqing Dong, Feng Lu.

   BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration.
METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system.
RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration.
CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

Keywords:  Adipose derived stem cells; CXCL12; CXCR4/RhoA; Migrasomes; Soft tissue regeneration; Stem cell recruitment

DOI:  https://doi.org/10.1186/s12951-024-02482-9
World J Stem Cells. 2024 Apr 26. 16(4): 334-352

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Jie-Yu Xiang, Lin Kang, Zi-Ming Li, Song-Lu Tseng, Li-Quan Wang, Tian-Hao Li, Zhu-Jun Li, Jiu-Zuo Huang, Nan-Ze Yu, Xiao Long.

  Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Keywords:  Biological scaffolds; Cellular activities enhancement; Extracellular matrix mimicry; Scaffold characteristics; Stem-cell-based therapy; Wound healing

DOI:  https://doi.org/10.4252/wjsc.v16.i4.334
Noncoding RNA Res. 2024 Sep;9(3): 945-953

Exploring the roles of non-coding RNAs in liver regeneration.

Penghui Li, Xiao Ma, Di Huang, Xinyu Gu.

  Liver regeneration (LR) is a complex process encompassing three distinct phases: priming, proliferation phase and restoration, all influenced by various regulatory factors. After liver damage or partial resection, the liver tissue demonstrates remarkable restorative capacity, driven by cellular proliferation and repair mechanisms. The essential roles of non-coding RNAs (ncRNAs), predominantly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNA (circRNA), in regulating LR have been vastly studied. Additionally, the impact of ncRNAs on LR and their abnormal expression profiles during this process have been extensively documented. Mechanistic investigations have revealed that ncRNAs interact with genes involved in proliferation to regulate hepatocyte proliferation, apoptosis and differentiation, along with liver progenitor cell proliferation and migration. Given the significant role of ncRNAs in LR, an in-depth exploration of their involvement in the liver's self-repair capacity can reveal promising therapeutic strategies for LR and liver-related diseases. Moreover, understanding the unique regenerative potential of the adult liver and the mechanisms and regulatory factors of ncRNAs in LR are crucial for improving current treatment strategies and exploring new therapeutic approaches for various liver-related diseases. This review provides a brief overview of the LR process and the ncRNA expression profiles during this process. Furthermore, we also elaborate on the specific molecular mechanisms through which multiple key ncRNAs regulate the LR process. Finally, based on the expression characteristics of ncRNAs and their interactions with proliferation-associated genes, we explore their potential clinical application, such as developing predictive indicators reflecting liver regenerative activity and manipulating LR processes for therapeutic purposes.

Keywords:  Cell proliferation; Clinical applications; Expression profile; Liver regeneration; ncRNAs

DOI:  https://doi.org/10.1016/j.ncrna.2024.04.003
BMJ Evid Based Med. 2024 Apr 29. pii: bmjebm-2023-112583. [Epub ahead of print]

Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies.

Zilong Bian, Lijuan Wang, Rong Fan, Jing Sun, Lili Yu, Meihong Xu, Paul R H J Timmers, Xia Shen, James F Wilson, Evropi Theodoratou, Xifeng Wu, Xue Li.

   OBJECTIVE: To investigate the associations across genetic and lifestyle factors with lifespan.
DESIGN: A longitudinal cohort study.
SETTING: UK Biobank.
PARTICIPANTS: 353 742 adults of European ancestry, who were recruited from 2006 to 2010 and were followed up until 2021.
EXPOSURES: A polygenic risk score for lifespan with long (<lowest quintile), intermediate (quintiles 2 to 4), and short (>highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, moderate alcohol consumption, regular physical activity, healthy body shape, adequate sleep duration, and a healthy diet, categorised into favourable, intermediate, and unfavourable lifestyles.
MAIN OUTCOME MEASURES: Lifespan defined as the date of death or the censor date minus the date of birth.
RESULTS: Of the included 353 742 participants of European ancestry with a median follow-up of 12.86 years, 24 239 death cases were identified. Participants were grouped into three genetically determined lifespan categories including long (20.1%), intermediate (60.1%), and short (19.8%), and into three lifestyle score categories including favourable (23.1%), intermediate (55.6%), and unfavourable (21.3%). The hazard ratio (HR) of death for individuals with a genetic predisposition to a short lifespan was 1.21 (95% CI 1.16 to 1.26) compared to those with a genetic predisposition to a long lifespan. The HR of death for individuals in the unfavourable lifestyle category was 1.78 (95% CI 1.71 to 1.85), compared with those in the favourable lifestyle category. Participants with a genetic predisposition to a short lifespan and an unfavourable lifestyle had 2.04 times (95% CI 1.87 to 2.22) higher rates of death compared with those with a genetic predisposition to a long lifespan and a favourable lifestyle. No multiplicative interaction was detected between the polygenic risk score of lifespan and the weighted healthy lifestyle score (p=0.10). The optimal combination of healthy lifestyles, including never smoking, regular physical activity, adequate sleep duration, and a healthy diet, was derived to decrease risk of premature death (death before 75 years).
CONCLUSION: Genetic and lifestyle factors were independently associated with lifespan. Adherence to healthy lifestyles could largely attenuate the genetic risk of a shorter lifespan or premature death. The optimal combination of healthy lifestyles could convey better benefits for a longer lifespan, regardless of genetic background.

Keywords:  PUBLIC HEALTH

DOI:  https://doi.org/10.1136/bmjebm-2023-112583