bims-cesemi 2024-03-03 papers

bims-cesemi

Biomed News

on Cellular senescence and mitochondria

Issue of 2024–03–03
fourteen papers selected by
Julio Cesar Cardenas, Universidad Mayor

Cellular senescence in the pathogenesis of ovarian dysfunction.
Insights into targeting cellular senescence with senolytic therapy: the journey from preclinical trials to clinical practice.
Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases.
Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.
Therapeutic effects of resveratrol on epigenetic mechanisms in age-related diseases: A comprehensive review.
Oxidized SOD1 accelerates cellular senescence in neural stem cells.
A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism.
PM2.5-induced premature senescence in HUVECs through the SIRT1/PGC-1α/SIRT3 pathway.
Resveratrol Shows Potent Senescence Reversal in Experimental Cellular Models of Particular Matter 2.5-induced Cellular Senescence in Human Dermal Papilla Cells.
Mitochondria in biology and medicine - 2023.
Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons.
Metabolic dysfunction and the development of physical frailty: an aging war of attrition.
Cell Senescence-Related Genes as Biomarkers for Prognosis and Immunotherapeutic Response in Colon Cancer.
Longevity and anti-aging effects of curcumin supplementation.

J Obstet Gynaecol Res. 2024 Feb 27.

Cellular senescence in the pathogenesis of ovarian dysfunction.

Miyuki Harada.

  The follicular microenvironment is crucial for normal ovarian function, and intra-ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens the adverse environment of various tissues and plays critical roles in chronological aging and various pathological conditions. Cellular senescence involves cell-cycle arrest, a senescence-associated secretory phenotype (SASP), macromolecular damage, and dysmetabolism. In this review, I summarize the latest knowledge regarding the role of cellular senescence in pathological conditions in the ovary, in the context of reproduction. Specifically, cellular senescence is known to impair follicular and oocyte health in cisplatin- and cyclophosphamide-induced primary ovarian insufficiency and to contribute to the pathogenesis of polycystic ovary syndrome (PCOS). In addition, cellular senescence is induced during the decline in ovarian reserve that is associated with chronological aging, endometriosis, psychological stress, and obesity, but it remains unclear whether it plays a causative role in these conditions. Finally, I discuss the potential for use of cellular senescence as a novel therapeutic target. The modification of SASP using a senomorphic and/or the elimination of senescent cells using a senolytic represent promising therapeutic strategies. Further elucidation of the role of cellular senescence in the effects of various insults on ovarian reserve, including chronological aging, as well as in pathogenesis of ovarian pathologies, including PCOS, may facilitate a new era of reproductive medicine.

Keywords:  cellular senescence; follicular microenvironment; ovary; senolytic; senomorphic

DOI:  https://doi.org/10.1111/jog.15918
Mech Ageing Dev. 2024 Feb 22. pii: S0047-6374(24)00018-6. [Epub ahead of print] 111918

Insights into targeting cellular senescence with senolytic therapy: the journey from preclinical trials to clinical practice.

Peng Chen, Yulai Wang, Benhong Zhou.

  Interconnected, fundamental aging processes are central to many illnesses and diseases. Cellular senescence is a mechanism that halts the cell cycle in response to harmful stimuli. Senescent cells (SnCs) can emerge at any point in life, and their persistence, along with the numerous proteins they secrete, can negatively affect tissue function. Interventions aimed at combating persistent SnCs, which can destroy tissues, have been used in preclinical models to delay, halt, or even reverse various diseases. Consequently, the development of small-molecule senolytic medicines designed to specifically eliminate SnCs has opened potential avenues for the prevention or treatment of multiple diseases and age-related issues in humans. In this review, we explore the most promising approaches for translating small-molecule senolytics and other interventions targeting senescence in clinical practice. This discussion highlights the rationale for considering SnCs as therapeutic targets for diseases affecting individuals of all ages.

Keywords:  Cellular senescence; Clinical application; Drug screening; Senescence-associated secretory phenotype; Senolytics

DOI:  https://doi.org/10.1016/j.mad.2024.111918
Front Cell Dev Biol. 2024 ;12 1287447

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases.

Wanyue Ding, Jingyu Chen, Lei Zhao, Shuang Wu, Xiaomei Chen, Hong Chen.

  Mitochondrial dysfunction is one of the hallmarks of cardiovascular aging. The leakage of mitochondrial DNA (mtDNA) is increased in senescent cells, which are resistant to programmed cell death such as apoptosis. Due to its similarity to prokaryotic DNA, mtDNA could be recognized by cellular DNA sensors and trigger innate immune responses, resulting in chronic inflammatory conditions during aging. The mechanisms include cGAS-STING signaling, TLR-9 and inflammasomes activation. Mitochondrial quality controls such as mitophagy could prevent mitochondria from triggering harmful inflammatory responses, but when this homeostasis is out of balance, mtDNA-induced inflammation could become pathogenic and contribute to age-related cardiovascular diseases. Here, we summarize recent studies on mechanisms by which mtDNA promotes inflammation and aging-related cardiovascular diseases, and discuss the potential value of mtDNA in early screening and as therapeutic targets.

Keywords:  cardiovasuclar diseases; inflammation; innate immunity; mitochondrial DNA; senescence

DOI:  https://doi.org/10.3389/fcell.2024.1287447
Aging Dis. 2024 Feb 27.

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Liyao Zheng, Shipei He, Hong Wang, Jinling Li, Yuanyuan Liu, Sijia Liu.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs) and senomorphics (compounds that alter intercellular communication and modulate the behavior of SnCs) have become hot research topics in the field of anti-aging. In addition, strategies such as combination therapies and immune-based approaches have also made significant progress in the field of anti-aging therapy. In this article, we discuss the latest research on anti-aging targeting SnCs and gain a deeper understanding of the mechanism of action and impact of different anti-aging strategies on aging and age-related diseases, with the aim of providing more effective references and therapeutic ideas for clinical anti-aging treatment in the face of the ever-grave challenges of aging and age-related diseases.

DOI: https://doi.org/10.14336/AD.2024.0206
Phytother Res. 2024 Feb 29.

Therapeutic effects of resveratrol on epigenetic mechanisms in age-related diseases: A comprehensive review.

Sale Zhang, Farzam Kiarasi.

  Recently, various studies have shown that epigenetic changes are associated with aging and age-related diseases. Both animal and human models have revealed that epigenetic processes are involved in aging mechanisms. These processes happen at multiple levels and include histone modification, DNA methylation, and changes in noncoding RNA expression. Consequently, changes in the organization of chromatin and DNA accessibility lead to the regulation of gene expression. With increasing awareness of the pivotal function of epigenetics in the aging process, researchers' attention has been drawn to how these epigenetic changes can be modified to prevent, stop, or reverse aging, senescence, and age-related diseases. Among various agents that can affect epigenetic, polyphenols are well-known phytochemicals found in fruits, vegetables, and plants. Polyphenols are found to modify epigenetic-related mechanisms in various diseases and conditions, such as metabolic disorders, obesity, neurodegenerative diseases, cancer, and cardiovascular diseases. Resveratrol (RSV) is a member of the stilbene subgroup of polyphenols which is derived from various plants, such as grapes, apples, and blueberries. Therefore, herein, we aim to summarize how RSV affects different epigenetic processes to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer's, Parkinson's, osteoporosis, and cardiovascular diseases.

Keywords:  Alzheimer; aging; cancer; epigenetic; methylation; resveratrol

DOI:  https://doi.org/10.1002/ptr.8176
Stem Cell Res Ther. 2024 Feb 27. 15(1): 55

Oxidized SOD1 accelerates cellular senescence in neural stem cells.

Teng Guan, Ying Guo, Ting Zhou, Qiang Yu, Jingyi Sun, Baoliang Sun, Guohui Zhang, Jiming Kong.

BACKGROUND: Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation. Once oxidized, it undergoes aberrant misfolding and gains toxic properties associated with age-related neurodegenerative disorders. The present study aims to examine the role of oxidized hSOD1 in the senescence of NSCs.
METHODS: NSCs prepared from transgenic mice expressing the wild-type hSOD1 gene were maintained in culture through repeated passages. Extracellular vesicles (EVs) were isolated from culture media at each passage. To selectively knock down oxidized SOD1 in NSCs and EVs, we used a peptide-directed chaperone-mediated protein degradation system named CT4 that we developed recently.
RESULTS: In NSCs expressing the hSOD1 from passage 5, we detected a significant increase of oxidized hSOD1 and an increased expression of biomarkers of cellular senescence, including upregulation of P53 and SA-β-Gal and cytoplasmic translocation of HMGB1. The removal of oxidized SOD1 remarkably increased the proliferation and stemness of the NSCs. Meanwhile, EVs derived from senescent NSCs carrying the wild-type hSOD1 contained high levels of oxidized hSOD1, which could accelerate the senescence of young NSCs and induce the death of cultured neurons. The removal of oxidized hSOD1 from the EVs abolished their senescence-inducing activity. Blocking oxidized SOD1 on EVs with the SOD1 binding domain of the CT4 peptide mitigated its toxicity to neurons.
CONCLUSION: Oxidized hSOD1 is a causal factor in the cellular senescence of NSCs. The removal of oxidized hSOD1 is a strategy to rejuvenate NSCs and to improve the quality of EVs derived from senescent cells.

DOI: https://doi.org/10.1186/s13287-024-03669-5
Nat Metab. 2024 Feb;6(2): 323-342

A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism.

Khaled Tighanimine, José Américo Nabuco Leva Ferreira Freitas, Ivan Nemazanyy, Alexia Bankolé, Delphine Benarroch-Popivker, Susanne Brodesser, Gregory Doré, Lucas Robinson, Paule Benit, Sophia Ladraa, Yara Bou Saada, Bertrand Friguet, Philippe Bertolino, David Bernard, Guillaume Canaud, Pierre Rustin, Eric Gilson, Oliver Bischof, Stefano Fumagalli, Mario Pende.

Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homoeostatic switch that results in glycerol-3-phosphate (G3P) and phosphoethanolamine (pEtN) accumulation links lipid metabolism to the senescence gene expression programme. Mechanistically, p53-dependent glycerol kinase activation and post-translational inactivation of phosphate cytidylyltransferase 2, ethanolamine regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression programme. Conversely, G3P phosphatase and ethanolamine-phosphate phospho-lyase-based scavenging of G3P and pEtN acts in a senomorphic way by reducing G3P and pEtN accumulation. Collectively, our study ties G3P and pEtN accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.

DOI: https://doi.org/10.1038/s42255-023-00972-y
Sci Total Environ. 2024 Feb 23. pii: S0048-9697(24)01316-0. [Epub ahead of print] 171177

PM2.5-induced premature senescence in HUVECs through the SIRT1/PGC-1α/SIRT3 pathway.

Qing Yan, Rao Zheng, Yi Li, Juan Hu, Meidi Gong, Manman Lin, Xuecong Xu, Jing Wu, Shikun Sun.

  Vascular endothelial cell senescence plays a pivotal role in the development of atherosclerosis. Recent studies have demonstrated that ambient fine particulate matter (PM2.5) induces stress-induced premature senescence (SIPS) in vascular endothelial cells. However, the precise mechanisms underlying this process remain to be fully elucidated. Cellular senescence is closely associated with reactive oxygen species (ROS), and emerging research has established a strong connection between the SIRT1/PGC-1α/SIRT3 signaling pathway and the antioxidant system in vascular endothelial cells. In this study, we aimed to investigate the impact of PM2.5 on vascular endothelial cell senescence and to elucidate the underlying mechanisms. Our findings revealed that PM2.5 exposure led to an increase in senescence-associated β-galactosidase (SA-β-gal) activity and the expression of the cell cycle-blocking proteins P53/P21 and P16 in human umbilical vein endothelial cells (HUVECs). Flow cytometry analysis demonstrated an elevated proportion of cells arrested in the G0/G1 phase after PM2.5 exposure. In addition, PM2.5-induced cellular senescence was attributed to the disruption of the cellular antioxidative defense system through the SIRT1/PGC-1α/SIRT3 signaling pathway. The expression of cellular senescence markers was reduced after targeted scavenging of mitochondrial ROS using MitoQ. Moreover, treatment with SRT1720, a SIRT1-specific activator, upregulated the SIRT1/PGC-1α/SIRT3 signaling pathway, restored the antioxidant system, and attenuated the expression of cellular senescence markers. Taken together, our results suggest that PM2.5 downregulates the SIRT1/PGC-1α/SIRT3 signaling pathway, resulting in impaired antioxidant defenses in HUVECs. This, in turn, allows for the accumulation of ROS, leading to inhibition of endothelial cell cycle progression and the onset of stress-induced senescence in HUVECs.

Keywords:  Antioxidant defense; HUVECs; PM(2.5); SIRT1/PGC-1α/SIRT3 pathway; Stress-induced premature senescence

DOI:  https://doi.org/10.1016/j.scitotenv.2024.171177
In Vivo. 2024 Mar-Apr;38(2):38(2): 665-673

Resveratrol Shows Potent Senescence Reversal in Experimental Cellular Models of Particular Matter 2.5-induced Cellular Senescence in Human Dermal Papilla Cells.

Zin Zin Ei, Thunwadee Srithawirat, Preedakorn Chunhacha, Chatchai Chaotham, Wanatchaporn Arunmanee, Preeyaphan Phookphan, Pithi Chanvorachote.

   BACKGROUND/AIM: Particular matter 2.5 (PM2.5) pollution is associated with senescence induction. Since the impact of PM2.5 on stem cell senescence and potential compounds capable of reversing this process are largely unknown, this study aimed to examine the senescence effects of PM2.5 on dermal papilla (DP) stem cells. Additionally, we explored the reversal of these effects using natural product-derived substances, such as resveratrol (Res) or Emblica fruits, soybean, and Thunbergia Laurifolia (EST) extract.
MATERIALS AND METHODS: Cell senescence was determined using the β-Galactosidase (SA-β-gal) assay. The senescence-associated secretory phenotype (SASP) was detected using real-time RT-PCR. For senescence markers, the mRNA and protein levels of p21 and p16 were measured using real-time RT-PCR and immunofluorescence analysis.
RESULTS: Subtoxic concentration of PM2.5 (50 μg/ml) induced senescence in DP cells. Resveratrol (50, 100 μM) and plant extracts (400, 800 μg/ml) reversed PM2.5-induced cell senescence. Treatment with Res or EST significantly decreased SA-β-gal staining in PM2.5-treated cells. Furthermore, Res and EST decreased the mRNA levels of SASP, including IL1α, IL7, IL8, and CXCL1. DP cells exposed to PM2.5 exhibited an increase in p21 and p16 mRNA and protein levels, which could be reversed by the addition of Res or EST. Res and EST could reduce p21 and p16 in senescent cells approximately 3- and 2-fold, respectively, compared to untreated senescent cells.
CONCLUSION: PM2.5 induced senescence in human DP stem cells. Res and EST extract potentially reverse the senescence phenotypes of such cells.

Keywords:  PM2.5; Senescence; dermal papilla cells; resveratrol

DOI:  https://doi.org/10.21873/invivo.13487
Mitochondrion. 2024 Feb 27. pii: S1567-7249(24)00011-4. [Epub ahead of print] 101853

Mitochondria in biology and medicine - 2023.

B Disha, Rohan Peter Mathew, Ashwin B Dalal, Ajay K Mahato, Kapaettu Satyamoorthy, Keshav K Singh, Kumarasamy Thangaraj, Periyasamy Govindaraj.

  Mitochondria are an indispensable part of the cell that plays a crucial role in regulating various signaling pathways, energy metabolism, cell differentiation, proliferation, and cell death. Since mitochondria have their own genetic material, they differ from their nuclear counterparts, and dysregulation is responsible for a broad spectrum of diseases. Mitochondrial dysfunction is associated with several disorders, including neuro-muscular disorders, cancer, and premature aging, among others. The intricacy of the field is due to the cross-talk between nuclear and mitochondrial genes, which has also improved our knowledge of mitochondrial functions and their pathogenesis. Therefore, interdisciplinary research and communication are crucial for mitochondrial biology and medicine due to the challenges they pose for diagnosis and treatment. The ninth annual conference of the Society for Mitochondria Research and Medicine (SMRM)- India, titled "Mitochondria in Biology and Medicine" was organized at the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India, on June 21-23, 2023. The latest advancements in the field of mitochondrial biology and medicine were discussed at the conference. In this article, we summarize the entire event for the benefit of researchers working in the field of mitochondrial biology and medicine.

Keywords:  Disease; Genetics; Metabolism; Mitochondria

DOI:  https://doi.org/10.1016/j.mito.2024.101853
bioRxiv. 2024 Feb 13. pii: 2024.02.12.579959. [Epub ahead of print]

Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons.

Nuo Jia, Dhasarathan Ganesan, Hongyuan Guan, Yu Young Jeong, Sinsuk Han, Marialaina Nissenbaum, Alexander W Kusnecov, Qian Cai.

Hyperphosphorylation and aggregation of microtubule-associated tau is a pathogenic hallmark of tauopathies and a defining feature of Alzheimer's disease (AD). Pathological tau is targeted by autophagy for clearance, but autophagy dysfunction is indicated in tauopathy. While mitochondrial bioenergetic failure has been shown to precede the development of tau pathology, it is unclear whether energy metabolism deficiency is involved in tauopathy-related autophagy defects. Here, we reveal that stimulation of anaplerotic metabolism restores defective oxidative phosphorylation (OXPHOS) in tauopathy which, strikingly, leads to enhanced autophagy and pronounced tau clearance. OXPHOS-induced autophagy is attributed to increased ATP-dependent phosphatidylethanolamine biosynthesis in mitochondria. Excitingly, early bioenergetic stimulation boosts autophagy activity and reduces tau pathology, thereby counteracting memory impairment in tauopathy mice. Taken together, our study sheds light on a pivotal role of bioenergetic dysfunction in tauopathy-linked autophagy defects and suggests a new therapeutic strategy to prevent toxic tau buildup in AD and other tauopathies.

DOI: https://doi.org/10.1101/2024.02.12.579959
Geroscience. 2024 Feb 24.

Metabolic dysfunction and the development of physical frailty: an aging war of attrition.

William A Fountain, Taylor S Bopp, Michael Bene, Jeremy D Walston.

  The World Health Organization recently declared 2021-2030 the decade of healthy aging. Such emphasis on healthy aging requires an understanding of the biologic challenges aging populations face. Physical frailty is a syndrome of vulnerability that puts a subset of older adults at high risk for adverse health outcomes including functional and cognitive decline, falls, hospitalization, and mortality. The physiology driving physical frailty is complex with age-related biological changes, dysregulated stress response systems, chronic inflammatory pathway activation, and altered energy metabolism all likely contributing. Indeed, a series of recent studies suggests circulating metabolomic distinctions can be made between frail and non-frail older adults. For example, marked restrictions on glycolytic and mitochondrial energy production have been independently observed in frail older adults and collectively appear to yield a reliance on the highly fatigable ATP-phosphocreatine (PCr) energy system. Further, there is evidence that age-associated impairments in the primary ATP generating systems (glycolysis, TCA cycle, electron transport) yield cumulative deficits and fail to adequately support the ATP-PCr system. This in turn may acutely contribute to several major components of the physical frailty phenotype including muscular fatigue, weakness, slow walking speed and, over time, result in low physical activity and accelerate reductions in lean body mass. This review describes specific age-associated metabolic declines and how they can collectively lead to metabolic inflexibility, ATP-PCr reliance, and the development of physical frailty. Further investigation remains necessary to understand the etiology of age-associated metabolic deficits and develop targeted preventive strategies that maintain robust metabolic health in older adults.

Keywords:  Aging; Energy; Frailty; Metabolism; Skeletal muscle

DOI:  https://doi.org/10.1007/s11357-024-01101-7
Biochem Genet. 2024 Feb 27.

Cell Senescence-Related Genes as Biomarkers for Prognosis and Immunotherapeutic Response in Colon Cancer.

Zhang Haibo, Lan Tianyun, Chen Xiaoman, Han Xiaoyan.

  Colon adenocarcinoma (COAD) stands out as the most prevalent malignancy diagnosed within the gastrointestinal tract, bearing substantial incidence and mortality rates. The processes of ageing and senescence intricately intertwine with tumorigenesis and immune regulation, concurrently exerting influence on the remodelling of the tumor microenvironment (TME). This phenomenon, in turn, significantly impacts the efficacy of immunotherapeutic interventions. Despite this awareness, the comprehensive understanding of the intricate interplay between cellular senescence and TME in the context of COAD remains elusive. Further inquiry is imperative to comprehensively gauge the relevance of cellular senescence-related genes (CSGs) in the realms of immune infiltration and the prognostication of COAD. Differentially expressed cell senescence-related genes (DE-CSGs) within COAD tumors and normal specimens were discerned through analysis of the TCGA-COAD dataset. Leveraging univariate, LASSO, and multivariate Cox regression analyses, we formulated a prognostic risk signature. Subsequent validation utilised two independent GEO datasets. Furthermore, a nomogram was devised to gauge the prognostic significance of this signature. Additionally, the immune landscape of the Cell Senescence-related Signature (CSS) was characterised using CIBERSORT and TIMER algorithms. The expression levels of CSGs were quantified through RT-PCR in COAD specimens. Drawing upon mRNA expression profiles of 191 DE-CSGs, we successfully established a 9-gene CSS, demonstrating its autonomy as a prognostic determinant for COAD patients. Those assigned high-risk scores exhibited an immunosuppressive phenotype, marked by elevated proportions of resting CD4+memory T cells and macrophages M0, correlating with diminished overall survival. Subsequent analyses uncovered that the amalgamation of CSS with the expression profiles of immune checkpoint key genes effectively predicted patient prognosis. Furthermore, patients with low-risk scores demonstrated a potential association with more favourable therapeutic outcomes in the context of immunotherapy. This study has culminated in the development of a prognostic risk signature grounded in cell senescence-related genes for COAD. We posit that the CSS plays a regulatory role in immune infiltration, emerging as a robust biomarker for prognosis and a predictive indicator for immunotherapeutic responsiveness within the COAD landscape.

Keywords:  Cellular senescence; Colon cancer; Immunotherapy; Prognosis; Tumor microenvironment

DOI:  https://doi.org/10.1007/s10528-024-10690-z
Geroscience. 2024 Feb 27.

Longevity and anti-aging effects of curcumin supplementation.

Mehran Izadi, Nariman Sadri, Amirhossein Abdi, Mohammad Mahdi Raeis Zadeh, Dorsa Jalaei, Mohammad Mahdi Ghazimoradi, Sara Shouri, Safa Tahmasebi.

  Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.

Keywords:  Aging; Curcumin; Longevity

DOI:  https://doi.org/10.1007/s11357-024-01092-5