Targeting organ-specific mitochondrial dysfunction to improve biological aging

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 262, P. 108710 - 108710

Published: Aug. 22, 2024

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites key regulators programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, mitochondrial dysfunction pivotal factor progressive age-related decline cellular homeostasis organ function. The current review examines recent advances understanding interplay between organ-specific aging. Thereby, we dissect molecular mechanisms underlying impairment associated with deterioration exploring DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated patterns, biogenesis, turnover, dynamics. We also highlight emerging therapeutic preclinical clinical tests that supposed rejuvenate such as antioxidants, biogenesis stimulators, modulators turnover Furthermore, discuss potential benefits challenges use interventions, emphasizing need for approaches given unique characteristics different tissues. conclusion, this highlights addressing mitigate aging, focusing on skin, liver, lung, brain, skeletal muscle, well reproductive, immune, cardiovascular systems. Based comprehensive multifaceted roles mitochondria, innovative may be developed optimized biological promote healthy across diverse

Language: Английский

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The relationship between vitamin A status and oxidative stress in animal production

Journal of Applied Animal Research, Journal Year: 2023, Volume and Issue: 51(1), P. 546 - 553

Published: July 27, 2023

Oxidative stress is caused by an imbalance between the production of harmful oxygen molecules and body's ability to repair their detrimental implications, leading reduced growth rates, increased disease susceptibility, decreased reproductive performance in animals. Vitamin A, comprising retinol, retinal, retinoic acid, crucial for normal growth, reproduction, vision. A possesses antioxidant properties directly scavenging reactive species, boosting enzyme activity, promoting defence mechanisms. Numerous studies have shown that livestock with adequate levels vitamin diet experience oxidative compared those deficiency. Moreover, supplementation can mitigate animals exposed stressful conditions like heat stress. Adequate status through dietary interventions improved animal management practices significantly benefit health well-being. However, further research still needed optimize dosing strategies fully understand relationship different species systems. Therefore, continued efforts are essential harness potential as effective tool mitigating improving welfare.

Language: Английский

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Anti-ageing interventions for the treatment of cardiovascular disease

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

As the global demographic landscape continues to shift towards an aged population, so does medical and socioeconomic burden of cardiovascular diseases. Indeed, ageing is one of, if not the, key risk factor for development However, there are currently no approved therapeutics that primarily target molecular cellular mechanisms underlying process itself. In this review, we present potential emerging anti-ageing strategies, including epigenetic rejuvenation, metabolic reprogramming, autophagy activation, as well senolytic anti-inflammatory therapies, in delaying or reversing age-related disorders, while considering sex differences. doing so, implicate processes pathogenesis several prevalent diseases, such atherosclerosis, hypertension, various types cardiomyopathies (including its hypertrophic, ischemic, dilated, diabetic, arrhythmogenic forms) heart failure, particularly with preserved ejection fraction. Finally, outline future challenges steps needed implementation these novel strategies clinical setting, aim challenging long-held notion a 'nonmodifiable'

Language: Английский

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Protein homeostasis in the aged and diseased heart

The Journal of Cardiovascular Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Protein homeostasis, the balance between protein synthesis and degradation, requires clearance of misfolded aggregated proteins is therefore considered to be an essential aspect establishing a physiologically effective proteome. Aging alters this balance, termed "proteostasis", resulting in progressive accumulation proteins. Defective proteostasis leads functional deterioration diverse regulatory processes during aging implicated etiology multiple pathological conditions underlying variety neurodegenerative diseases age-dependent cardiovascular disease. Detergent-insoluble aggregates have been reported by us both aged hypertensive hearts. The constituents were found overlap with seen such as Alzheimer's Therefore, targeting these components may promising therapeutic strategy for pathologies associated aging, ischemia, and/or hypertension.

Language: Английский

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Hydrogen sulfide ameliorates endothelial dysfunction in aging arteries by regulating ferroptosis

Nitric Oxide, Journal Year: 2023, Volume and Issue: 140-141, P. 77 - 90

Published: Oct. 22, 2023

Language: Английский

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Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

Chinese Medicine, Journal Year: 2024, Volume and Issue: 15(02), P. 15 - 26

Published: Jan. 1, 2024

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for Qi-invigorating properties the five visceral organs. Our laboratory has shown that action of tonifying herbs linked to increased mitochondrial ATP generation and an enhancement glutathione redox status. To explore whether Sch can exert actions across various tissues, we investigated effects treatment on status multiple mouse tissues ex vivo. In line with TCM theory, which posits Zheng Qi relies function organs, also examined B's impact natural killer cell activity antigen-induced splenocyte proliferation, both serving indirect measures Qi. findings revealed consistently enhanced improved tissues. This boost was associated stimulated innate adaptive immune responses, marked by T/B potentially through

Language: Английский

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Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(11), P. 1534 - 1534

Published: Oct. 31, 2023

Targeted nitric oxide production is relevant for maintaining cellular energy production, protecting against oxidative stress, regulating cell death, and promoting neuroprotection. This study aimed to characterize the putative interaction of nitric-oxide synthase with mitochondrial proteins. The primary finding this that cytochrome c oxidase (CCO) subunit IV (CCOIV) associated directly NOS in brain mitochondria when calcium ions are present. matrix side CCOIV binds N-terminus NOS, supported by abrogation binding antibodies towards NOS. Evidence supporting between was provided coimmunoprecipitation from detergent-solubilized whole rat crude preparations using domain interacts identified a series overlapping peptides derived sequence CCOIV. As not only activate but also facilitate docking CCOIV, points dynamic mechanism controlling bioenergetics changes, thereby adapting demands.

Language: Английский

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Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage

Gynecologic and Obstetric Investigation, Journal Year: 2024, Volume and Issue: 89(2), P. 120 - 130

Published: Jan. 1, 2024

<b><i>Objectives:</i></b> We investigated the potential of glutathione to protect ovarian function in rats exposed cyclophosphamide by measuring serum anti-Mullerian hormone (AMH) levels, follicle counts, and related parameters. <b><i>Design:</i></b> Forty-two adult female Sprague-Dawley were randomly divided into six groups treated with various combinations cyclophosphamide, glutathione, sodium chloride. On day 21, anesthetized, their ovaries removed for examination. <b><i>Participants/Materials, Setting, Methods:</i></b> Histopathological examination, AMH concentrations, AMH-positive staining percentages analyzed. Statistical analysis was performed using a one-way variance Tukey’s test, significance set at <i>p</i> &lt; 0.05. Secondary measures encompassed histopathological examination follicles. <b><i>Results:</i></b> Significant differences observed parameters, concentrations among groups. Group 2 (treated cyclophosphamide) had lowest primordial, primary, secondary, antral counts highest atretic count. 6, 200 mg/kg showed improved compared those group 2. Reducing dose 100 ineffective. <b><i>Limitations:</i></b> This an experimental animal investigation comparatively modest sample size. Experimental studies should be conducted determine optimal dosage duration therapy. Information gathered from model may not yield precisely similar outcomes humans; therefore, additional investigations are necessary examine impact on women experiencing POI. <b><i>Conclusions:</i></b> The anti-oxidative protective effect directly administered demonstrated first time. Low-dose ineffective, whereas high yielded significant protection against cyclophosphamide. Our findings provide valuable insights supplementing clinical trials effects damage.

Language: Английский

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Glutathione Upregulates the Expression of KATP Channels and Vasorelaxation Responses and Inhibits mPTP Opening and Oxidative Stress in the Heart Mitochondria of Old Rats

BioMed Research International, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 10

Published: May 24, 2023

In the present work, we investigated effect of exogenous glutathione in old rats on expression ATP-sensitive potassium (KATP) channels, mitochondrial permeability transition pore (mPTP) opening heart, and vasorelaxation responses isolated aortic rings to activation KATP channels.Experiments were performed adult (6 months) (24 male Wistar rats, which divided into three groups: adult, old, glutathione-treated rats. Glutathione was injected intraperitoneally at a dose 52 mg/kg 1 hour before studies. The mRNA channels determined using reverse transcription real-time polymerase chain reaction analysis. administration mPTP opening, relaxation rings, oxidative stress markers studied.It shown that levels Kir6.1, Kir6.2, SUR1 subunits reduced significantly increased (by 8.3, 2.8, 13.1, 1.5-fold, respectively), whereas (hydrogen peroxide, diene conjugates, malondialdehyde, rate superoxide generation) heart mitochondria reduced. Relaxation response actions channel openers flocalin pinacidil animals, prevented by glibenclamide.Thus, resulted significant increase decrease stress. This accompanied inhibition enhancement channels.

Language: Английский

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MITOCHONDRIAL DYSFUNCTION IN ACUTE CARDIOTOXIC EFFECT OF DOXORUBICIN IN ADULT RATS

Fìzìologìčnij žurnal, Journal Year: 2023, Volume and Issue: 69(6), P. 3 - 14

Published: Nov. 10, 2023

Doxorubicin is a potent cytotoxic antibiotic that the most widely prescribed in world and effective against wide range of cancers. At same time, cardiotoxic effects this drug often require discontinuation treatment before effect achieved. Mitochondria are important mediators cellular life, cardiomyocyte death due to mitochondrial mechanisms internal killing basis many heart diseases. The aim study was investigate short-term doxorubicin administration on Ca2+-induced opening nonspecific permeability transition pore (mPTP) adult rats. To reproduce evaluate acute cardiotoxicity rats, which main complication patients taking doxorubicin, cardiomyopathy model used. A comparative ultrastructural myocardial tissues performed at total cumulative doses 8, 13 15 mg/kg administered intraperitoneally spread over two days. It shown caused damage myofibrillar apparatus, mitochondria cardiomyocytes exhibited dose-dependent effect. Therefore, further experiments were carried out indicative dose, namely mg/kg. We have content reactive oxygen species mitochondria, namely, •O2-, Н2О2, •ОН, increased after by 10.5, 5.3 3.4 times, respectively, indicating significant increase free radical processes. endogenous H2S decreased 2.6 times. This activated mPTP rat heart: amplitude spontaneous swelling doubled, 53% compared control, an sensitivity Ca2+ observed all applied concentrations. Thus, resulted induction opening, led death.

Language: Английский

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