Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging – from theory to practice DOI Creative Commons
Carla Luís, A. Maduro, Paula Pereira

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 8, 2022

Aging is a natural physiological process, but one that poses major challenges in an increasingly aging society prone to greater health risks such as diabetes, cardiovascular disease, cancer, frailty, increased susceptibility infection, and reduced response vaccine regimens. The loss of capacity for cell regeneration the surrounding tissue microenvironment itself conditioned by genetic, metabolic, even environmental factors, nutrition. senescence immune system (immunosenescence) represents challenge, especially when associated with presence age-related chronic inflammation (inflammaging) affecting metabolic programming cells (immunometabolism). These aspects are linked poorer outcomes therefore present opportunity host-directed interventions aimed at both eliminating senescent curbing underlying inflammation. Senotherapeutics class drugs products delay, prevent, or reverse process – senolytics; inhibit senescence-associated secretory phenotype senomorphics. Natural senotherapeutics from food sources nutritional may constitute interesting way achieve better age-associated through personalized In this sense, authors herein framework intervention targeting immunosenescence immunometabolism, identifying research gaps area, gathering information on concluded ongoing clinical trials subject. Also, we future directions ideation possibilities field.

Language: Английский

Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy DOI Creative Commons
Hanxin Liu,

Qixia Xu,

Halidan Wufuer

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 23(1)

Published: July 20, 2023

Abstract Aging is a major risk factor for most chronic disorders, which cellular senescence one of the central hallmarks. Senescent cells develop pro‐inflammatory senescence‐associated secretory phenotype (SASP), significantly contributes to organismal aging and age‐related disorders. Development senotherapeutics, an emerging class therapeutic agents target senescent cells, allows effectively delay alleviate pathologies. Here we report preliminary outputs from screening natural medicinal agent (NMA) library senotherapeutic candidates validated several with prominent potential as senomorphics. Rutin, phytochemical constituent found in number plants, showed remarkable capacity targeting by dampening expression full spectrum SASP. Further analysis indicated that rutin restrains acute stress‐associated (ASAP) specifically interfering interactions ATM HIF1α, master regulator systemic homeostasis activated during senescence, TRAF6, part key signaling axis supporting ASAP development toward Conditioned media produced stromal enhanced malignant phenotypes prostate cancer including vitro proliferation, migration, invasion, more importantly, chemoresistance, while remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, treatment outcome was substantially improved upon combination chemotherapeutic rutin. Our study provides proof concept senomorphic agent, presents effective avenue alleviating pathologies cancer.

Language: Английский

Citations

71
Antiaging agents: safe interventions to slow aging and healthy life span extension DOI Creative Commons
Ji‐Kai Liu

Natural Products and Bioprospecting, Journal Year: 2022, Volume and Issue: 12(1)

Published: May 9, 2022

Abstract Human longevity has increased dramatically during the past century. More than 20% of 9 billion population world will exceed age 60 in 2050. Since last three decades, some interventions and many preclinical studies have been found to show slowing aging increasing healthy lifespan organisms from yeast, flies, rodents nonhuman primates. The are classified into two groups: lifestyle modifications pharmacological/genetic manipulations. Some genetic pathways characterized a specific role controlling lifespan. Thus, all genes potential antiaging targets. Currently, compounds target calorie-restriction mimetic, autophagy induction, putative enhancement cell regeneration, epigenetic modulation gene activity such as inhibition histone deacetylases DNA methyltransferases, under development. It appears evident that exploration new targets for these agents based on biogerontological research provides an incredible opportunity healthcare pharmaceutical industries. present review focus properties slow life span extension natural products various biological resources, endogenous substances, drugs, synthetic compounds, well mechanisms evaluation. These bioactive could benefit discussed.

Language: Английский

Citations

70
Discovery of senolytics using machine learning DOI Creative Commons
Vanessa Smer-Barreto, Andrea Quintanilla,

Richard Elliott

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 10, 2023

Abstract Cellular senescence is a stress response involved in ageing and diverse disease processes including cancer, type-2 diabetes, osteoarthritis viral infection. Despite growing interest targeted elimination of senescent cells, only few senolytics are known due to the lack well-characterised molecular targets. Here, we report discovery three using cost-effective machine learning algorithms trained solely on published data. We computationally screened various chemical libraries validated senolytic action ginkgetin, periplocin oleandrin human cell lines under modalities senescence. The compounds have potency comparable senolytics, show that has improved over its target as compared best-in-class alternatives. Our approach led several hundred-fold reduction drug screening costs demonstrates artificial intelligence can take maximum advantage small heterogeneous data, paving way for new open science approaches early-stage discovery.

Language: Английский

Citations

54
Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases DOI

Qing Zeng,

Yongzhen Gong,

Neng Zhu

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102294 - 102294

Published: April 5, 2024

Language: Английский

Citations

33
Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases DOI Creative Commons
Bowen Yang, Yumeng Lin, Yibo Huang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103032 - 103032

Published: Jan. 21, 2024

Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and cofactor for diverse enzymes transcription factors, thereby exerting influence over their activity function. has emerged pivotal biomarker various diseases, particularly those associated with oxidative stress, inflammation, aging. Recent clinical investigations have underscored the significance of in disease diagnosis, treatment, mechanistic elucidation. Despite its paramount importance, intricate interplay between senescence-a condition characterized irreversible growth arrest induced multiple aging stimuli-remains inadequately understood. In this review, our objective to present comprehensive up-to-date overview structure function Trx, involvement signaling pathways senescence, association age-related well potential therapeutic target. Our review aims elucidate novel extensive role senescence while highlighting implications diseases.

Language: Английский

Citations

20
The role of cellular senescence in neurodegenerative diseases DOI Creative Commons
Yating Wang, Kamil Kuča, You Li

et al.

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(8), P. 2393 - 2408

Published: May 15, 2024

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of hallmarks (p16 p21) elevated β-galactosidase activity in vitro vivo ND models. These contribute to the deposition β-amyloid tau-protein tangles. Selective clearance SASP regulation by inhibiting p38/mitogen-activated protein kinase nuclear factor kappa B signaling attenuate load prevent tangle deposition, thereby improving cognitive performance AD mouse In addition, telomere shortening, a biomarker, is associated with increased risks. Telomere dysfunction causes senescence, stimulating tumor necrosis factor-α, IL-1β secretions. The forced telomerase activators prevents yielding considerable neuroprotective effects. This review elucidates mechanism pathogenesis, suggesting strategies eliminate or restore normal phenotype for treating such diseases.

Language: Английский

Citations

16
Mitochondria-targeted senotherapeutic interventions DOI
Mehmet Can Atayik, Ufuk Çakatay

Biogerontology, Journal Year: 2022, Volume and Issue: 23(4), P. 401 - 423

Published: July 4, 2022

Language: Английский

Citations

42
Characterization of cellular senescence in doxorubicin-induced aging mice DOI
Tianyue Sun,

Lanxin Zhang,

Jiali Feng

et al.

Experimental Gerontology, Journal Year: 2022, Volume and Issue: 163, P. 111800 - 111800

Published: April 6, 2022

Language: Английский

Citations

41
Cellular senescence in asthma: from pathogenesis to therapeutic challenges DOI Creative Commons
Rongjun Wan, Prakhyath Srikaram,

Vineeta Guntupalli

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104717 - 104717

Published: July 11, 2023

Asthma is a heterogeneous chronic respiratory disease that impacts nearly 10% of the population worldwide. While cellular senescence normal physiological process, accumulation senescent cells considered trigger transforms physiology into pathophysiology tissue/organ. Recent advances have suggested significance in asthma. With this review, we focus on literature regarding and stress responses link triggers asthma to senescence, including telomere shortening, DNA damage, oncogene activation, oxidative-related senescence-associated secretory phenotype (SASP). The association phenotypes, airway inflammation remodeling, was also reviewed. Importantly, several approaches targeting such as senolytics senomorphics, emerged promising strategies for treatment. Therefore, might represent mechanism asthma, senescence-related molecules pathways could be targeted therapeutic benefit.

Language: Английский

Citations

33
The impact of cellular senescence in human adipose tissue DOI Creative Commons
Annika Nerstedt, Ulf Smith

Journal of Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 17(3), P. 563 - 573

Published: May 17, 2023

Abstract In the last decades prevalence of obesity has increased dramatically, and worldwide epidemic related metabolic diseases contributed to an interest for adipose tissue (AT), primary site storage lipids, as a metabolically dynamic endocrine organ. Subcutaneous AT is depot with largest capacity store excess energy when its limit reached hypertrophic obesity, local inflammation, insulin resistance ultimately type 2 diabetes (T2D) will develop. Hypertrophic also associated dysfunctional adipogenesis, depending on inability recruit differentiate new mature cells. Lately, cellular senescence (CS), aging mechanism defined irreversible growth arrest that occurs in response various stressors, such telomere shortening, DNA damage oxidative stress, gained lot attention regulator tissues aging-associated conditions. The abundance senescent cells increases not only but independent age. Senescent characterized by cells, decreased sensitivity lipid storage. resident progenitor (APC), non-proliferating microvascular endothelial are affected burden. Dysfunctional APC have both impaired adipogenic proliferative capacity. Interestingly, human from obese hyperinsulinemic individuals been shown re-enter cell cycle senesce, which indicates endoreplication. CS was found be more pronounced T2D individuals, compared matched non-diabetic Graphical abstract Factors

Language: Английский

Citations

26