Role of mitochondrial alterations in human cancer progression and cancer immunity

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: July 31, 2023

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, metabolism, apoptosis, and calcium redox homeostasis. Although “Warburg effect,” in which cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to progression still unclear. This review discusses recent progress alterations DNA (mtDNA) dynamics malignant progression. Moreover, we integrate possible regulatory mechanism dysfunction–mediated retrograde signaling pathways, including mitochondrion-derived molecules (reactive species, calcium, oncometabolites, mtDNA) stress response pathways (mitochondrial unfolded protein integrated response) provide therapeutic targets. Furthermore, discuss findings on role mitochondria immune function reveal impact tumor microenvironment remodeling immunity. Targeting might improve immunotherapy. These suggest that targeting malignancy modulating immunity be promising treatment strategies patients precise personalized medicine against cancer.

Language: Английский

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Mitochondrial stress and mitokines in aging

Aging Cell, Journal Year: 2023, Volume and Issue: 22(2)

Published: Jan. 15, 2023

Abstract Mitokines are signaling molecules that enable communication of local mitochondrial stress to other mitochondria in distant cells and tissues. Among those FGF21, GDF15 (both expressed the nucleus) several mitochondrial‐derived peptides, including humanin. Their responsiveness induces mitokine‐signaling response for example exercise, following challenges skeletal muscle. Such is emerging as an important mediator exercise‐derived dietary strategy‐related molecular systemic health benefits, healthy aging. A compensatory increase mitokine synthesis secretion could preserve function overall cellular vitality. Conversely, resistance against actions may also develop. Alterations mitokine‐levels, therefore mitokine‐related inter‐tissue cross talk, associated with general aging processes influence development age‐related chronic metabolic, cardiovascular neurological diseases; whether these changes contribute or represent “rescue factors” remains be conclusively shown. The aim present review summarize expanding knowledge on mitokines, potential modulate them by lifestyle their involvement diseases. We highlight importance well‐balanced preventive therapeutic properties maintaining homeostasis sensitivity but risks arising from dysregulation mitokines. While reduced levels impair inter‐organ crosstalk, excessive concentrations can have deleterious consequences conditions such cancer heart failure. Preservation achieved regular exercise increased lifespan.

Language: Английский

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Mitochondrial Structure and Function in Human Heart Failure

Circulation Research, Journal Year: 2024, Volume and Issue: 135(2), P. 372 - 396

Published: July 4, 2024

Despite clinical and scientific advancements, heart failure is the major cause of morbidity mortality worldwide. Both mitochondrial dysfunction inflammation contribute to development progression failure. Although crucial reparative healing following acute cardiomyocyte injury, chronic damages heart, impairs function, decreases cardiac output. Mitochondria, which comprise one third volume, may prove a potential therapeutic target for Known primarily energy production, mitochondria are also involved in other processes including calcium homeostasis regulation cellular apoptosis. Mitochondrial function closely related morphology, alters through dynamics, thus ensuring that needs cell met. However, failure, changes substrate use lead impaired myocyte function. This review discusses cristae role contact site organizing system complex ultrastructure changes. Additionally, this covers mitochondria-endoplasmic reticulum sites, communication via nanotunnels, altered metabolite production during We highlight these often-neglected factors promising targets

Language: Английский

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Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR)

The journal of nutrition health & aging, Journal Year: 2025, Volume and Issue: 29(1), P. 100401 - 100401

Published: Jan. 1, 2025

Aging, a universal and inevitable process, is characterized by progressive accumulation of physiological alterations functional decline over time, leading to increased vulnerability diseases ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) exercise, significantly modulate aging phenotypes. Physical exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance function, reduce the burden non-communicable chronic including cardiometabolic disease, cancer, musculoskeletal neurological conditions, respiratory well premature mortality. influences cellular molecular drivers biological aging, slowing rates-a foundational aspect geroscience. Thus, PA serves both preventive medicine therapeutic agent in pathological states. Sub-optimal levels correlate with disease prevalence populations. Structured prescriptions should therefore be customized monitored like any other medical treatment, considering dose-response relationships specific adaptations necessary for intended outcomes. Current guidelines recommend multifaceted regimen that includes aerobic, resistance, balance, flexibility training through structured incidental (integrated lifestyle) activities. Tailored programs have proven effective helping older adults maintain their capacities, extending enhancing quality life. Particularly important are anabolic exercises, such Progressive resistance (PRT), which indispensable maintaining improving capacity adults, particularly those frailty, sarcopenia osteoporosis, hospitalized residential aged care. Multicomponent interventions include cognitive tasks hallmarks frailty (low body mass, strength, mobility, level, energy) thus preventing falls optimizing during aging. Importantly, PA/exercise displays characteristics varies between individuals, necessitating personalized modalities tailored conditions. Precision remains significant area further research, given global impact broad effects PA. Economic analyses underscore cost benefits programs, justifying broader integration into care adults. However, despite these benefits, far from fully integrated practice people. Many healthcare professionals, geriatricians, need more incorporate directly patient care, whether settings hospitals, outpatient clinics, Education about use isolated adjunctive treatment geriatric syndromes would do much ease problems polypharmacy widespread prescription potentially inappropriate medications. This intersection prescriptive practices offers promising approach well-being An strategy combines pharmacotherapy optimize vitality independence people whilst minimizing adverse drug reactions. consensus provides rationale promotion, prevention, management strategies Guidelines included dosages efficacy randomized controlled trials. Descriptions beneficial changes, attenuation phenotypes, role disability provided. The sarcopenia, neuropsychological emphasized. Recommendations bridge existing knowledge implementation gaps integrate mainstream Particular attention paid it applies geroscience, inter-individual variability adaptation demonstrated adult cohorts. Overall, this foundation applying current base an population span

Language: Английский

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Pathological mechanisms of kidney disease in ageing

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(9), P. 603 - 615

Published: July 18, 2024

Language: Английский

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Mitochondrial dysfunction and its association with age-related disorders

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: July 2, 2024

Aging is a complex process that features functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts because mitochondria regulate cellular energy, balance, calcium levels. integrity maintained by mitophagy, which helps maintain homeostasis, prevents ROS production, protects against mtDNA damage. However, increased uptake stress can disrupt membrane potential permeability, leading to apoptotic cascade. This disruption causes production of free radicals, modification accumulation DNA mutations, contribute aging. dysfunction, resulting from structural linked age-related degenerative diseases. review focuses on its implications disorders, anti-aging strategies through targeting

Language: Английский

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A Four-Week Mobile App–Based Tele-Rehabilitation Program Versus Conventional In-Person Rehabilitation in Elderly Patients with Sarcopenia: A Randomized Controlled Trial (Preprint)

Journal of Medical Internet Research, Journal Year: 2025, Volume and Issue: 27, P. e67846 - e67846

Published: Jan. 15, 2025

Background Sarcopenia is closely associated with a poor quality of life and mortality, its prevention treatment represent critical area research. Resistance training an effective for older adults sarcopenia. However, they often face challenges when receiving traditional rehabilitation treatments at hospitals. Objective We aimed to compare the effects digital program those therapist-supervised on Methods In total, 58 sarcopenia were recruited offline randomized (1:1) into 2 groups: telerehabilitation group (TRG, n=29, 50%) in-person (IRG, 50%). Both groups underwent 4-week resistance targeting 6 major muscle groups. The TRG received exercise guidance via mobile app, while IRG from therapist. Offline assessments body composition, grip strength, balance using 30-Second Arm Curl Test (30SACT), Sitting-to-Rising (30SSRT), quadriceps femoris extension peak torque (EPT) total power (ETP), Berg Balance Scale (BBS), Timed Up-and-Go (TUGT), 6-Minute Walk (6MWT), Instrumental Activities Daily Living (IADL) scale, conducted before after intervention. Results Of patients, 51 (88%; TRG: n=24, 47%; IRG: n=27, 53%) completed trial. After 4 weeks intervention, mean strength increased 18.10 (SD 5.56) 19.92 5.90) kg in (P=.02) 18.59 5.95) 19.59 6.11) (P=.01). 30SACT 30SSRT scores 12.48 2.68) 14.94 3.68) times (P=.01) 15.16 7.23) 16.58 8.42) (P=.045), respectively, 12.25 4.19) 14.68 4.36) (P=.003) 14.31 4.04) 16.25 4.91) (P=.01), IRG. EPT 26.19 10.26) 35.00 13.74) Nm (P=.004) 26.95 11.81) 32.74 12.33) BBS significantly improved both (P<.001), score increasing by 3.19 2.86) points 3.06 2.44) points. Neither exhibited significant within-group changes TUGT or 6MWT. reported improvements IADL (TRG: P=.04; P=.02). Between-group comparisons revealed no differences all indicators. Conclusions A remote improving balance, sarcopenia, comparable supervised physical Telerehabilitation may be convenient alternative who have limited access resources. Trial Registration ChiCTR 2300071648; https://www.chictr.org.cn/showprojEN.html?proj=196313

Language: Английский

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Engineered mitochondria in diseases: mechanisms, strategies, and applications

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 3, 2025

Abstract Mitochondrial diseases represent one of the most prevalent and debilitating categories hereditary disorders, characterized by significant genetic, biological, clinical heterogeneity, which has driven development field engineered mitochondria. With growing recognition pathogenic role damaged mitochondria in aging, oxidative inflammatory diseases, cancer, application expanded to those non-hereditary contexts (sometimes referred as mitochondria-related diseases). Due their unique non-eukaryotic origins endosymbiotic relationship, are considered highly suitable for gene editing intercellular transplantation, remarkable progress been achieved two promising therapeutic strategies—mitochondrial artificial mitochondrial transfer (collectively this review) over past decades. Here, we provide a comprehensive review mechanisms recent advancements applications, alongside concise summary potential implications supporting evidence from preclinical studies. Additionally, an emerging potentially feasible approach involves ex vivo editing, followed selection holds overcome limitations such reduced operability introduction allogeneic thereby broadening applicability

Language: Английский

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Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Biology, Journal Year: 2023, Volume and Issue: 12(4), P. 558 - 558

Published: April 6, 2023

Background: Senescence is a cellular aging process in all multicellular organisms. It characterized by decline functions and proliferation, resulting increased damage death. These conditions play an essential role significantly contribute to the development of age-related complications. Humanin mitochondrial-derived peptide (MDP), encoded mitochondrial DNA, playing cytoprotective preserve function cell viability under stressful senescence conditions. For these reasons, humanin can be exploited strategies aiming counteract several processes involved aging, including cardiovascular disease, neurodegeneration, cancer. Relevance disease: appears decay organ tissue function, it has also been related diseases, such as conditions, cancer, diabetes. In particular, senescent cells produce inflammatory cytokines other pro-inflammatory molecules that participate diseases. Humanin, on hand, seems contrast known diseases promoting death damaged or malfunctioning contributing inflammation often associated with them. Both humanin-related mechanisms are complex have not fully clarified yet. Further research needed thoroughly understand disease identify potential interventions target them order prevent treat Objectives: This systematic review aims assess underlying link connecting senescence, humanin, disease.

Language: Английский

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Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e27749 - e27749

Published: March 1, 2024

BackgroundDiabetic kidney disease (DKD) stands as a primary contributor to end-stage renal disease, associated with heightened mortality in cardiovascular diseases. This study aimed explore the impact of an eight-week high-intensity interval training (HIIT) on injury diabetic rats.Methods.Twenty-eight male Wistar rats were randomly allocated into four groups: healthy control (CTL), (DC), exercise (EX), and diabetes-exercise (D + EX). Induction diabetes DC D EX groups occurred through two-month high-fat diet followed by single dose 35 mg/kg streptozotocin (STZ). Rats underwent 4–10 intervals HIIT (80–100% Vmax) over 8 weeks. Subsequently, pathological biochemical parameters assessed serum tissue experimental groups.Results.In group, led elevated damage, glomerulosclerosis, fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index, animal weight, dysfunction, albuminuria, glomerular filtration rate. Additionally, levels fetuin-A increased, along KIM-1. Mechanistically, induction resulted inflammation elevating tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin 6 (IL-6), while reducing IL-10 increasing IL-6/IL-10 ratio. Furthermore, triggered oxidative stress, evidenced increased Malondialdehyde (MDA) decreased glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD). mitigated adverse effects group compared group.Conclusion.Our findings suggest that ameliorates type 2 (T2D)-induced damage mitigating inflammation, lowering fetuin-A, bolstering antioxidant defenses. highlights potential time-efficient intervention nephropathy.

Language: Английский

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