Aging Hallmarks and the Role of Oxidative Stress

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 651 - 651

Published: March 6, 2023

Aging is a complex biological process accompanied by progressive decline in the physical function of organism and an increased risk age-related chronic diseases such as cardiovascular diseases, cancer, neurodegenerative diseases. Studies have established that there exist nine hallmarks aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, (ix) altered communication. All these alterations been linked to sustained systemic inflammation, mechanisms contribute timing not clearly determined yet. Nevertheless, dysfunction one most important contributing process. Mitochondria primary endogenous source reactive oxygen species (ROS). During ATP production elevated ROS together with antioxidant defense. Elevated levels can cause oxidative stress severe damage cell, organelle membranes, DNA, lipids, proteins. This contributes phenotype. In this review, we summarize recent advances emphasis on production.

Language: Английский

---

GDF15 promotes weight loss by enhancing energy expenditure in muscle

Nature, Journal Year: 2023, Volume and Issue: 619(7968), P. 143 - 150

Published: June 28, 2023

Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, most individuals, usually not maintained partly due to physiological adaptations suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment rodents fed high-fat diet recombinant growth differentiating factor 15 (GDF15) reduces obesity improves glycaemic control through glial-cell-derived neurotrophic family receptor α-like (GFRAL)-dependent suppression food intake4-7. Here we find that, addition suppressing appetite, GDF15 counteracts compensatory reductions eliciting greater (NAFLD) compared caloric alone. This effect maintain expenditure during calorie requires GFRAL-β-adrenergic-dependent signalling axis increases acid oxidation calcium futile cycling skeletal muscle mice. These data indicate therapeutic targeting GDF15-GFRAL pathway may be useful maintaining restriction.

Language: Английский

---

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

---

Adipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury

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

Published: Jan. 5, 2023

Abstract Fibro-adipogenic progenitors (FAPs) play a crucial role in skeletal muscle regeneration, as they generate favorable niche that allows satellite cells to perform efficient regeneration. After injury, FAP content increases rapidly within the injured muscle, origin of which has been attributed their proliferation itself. However, recent single-cell RNAseq approaches have revealed phenotype and functional heterogeneity FAPs, raising question how this differentiation regenerative subtypes occurs. Here we report FAP-like residing subcutaneous adipose tissue (ScAT), stromal (ASCs), are released from ScAT response injury. Additionally, find ASCs infiltrate damaged via platelet-dependent mechanism thus contribute heterogeneity. Moreover, show either blocking infiltration or removing source impair Collectively, our data reveal is an unsuspected physiological reservoir support underlining beneficial relationship between fat.

Language: Английский

---

A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 147, P. 112636 - 112636

Published: Jan. 17, 2022

Sarcopenia characterized by reduced skeletal muscle mass and decreased strength is increasing in prevalence globally. The pathophysiology of sarcopenia related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction food intake, advanced age, low body index, physical activity. Recently, has been reported be associated with cognitive decline, the common risk between memory loss were observed cohort studies. Many researchers suggested that vascular disorder, such as atherosclerosis alteration mechanisms caused changes myokine secretion. We herein review emerging evidence on strong link impairment sarcopenia, focusing secretion dysfunction, provide an understanding relevant crucial determinants decline sarcopenia.

Language: Английский

---

The Potential Role of Growth Differentiation Factor 15 in COVID-19: A Corollary Subjective Effect or Not?

Diagnostics, Journal Year: 2022, Volume and Issue: 12(9), P. 2051 - 2051

Published: Aug. 24, 2022

Coronavirus disease 2019 (COVID-19) is primarily caused by various forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants. COVID-19 characterized hyperinflammation, oxidative stress, multi-organ injury (MOI)-like lung (ALI) and distress (ARDS). Different biomarkers are used in the assessment severity including D-dimer, ferritin, lactate dehydrogenase (LDH), hypoxia-inducible factor (HIF). Interestingly, growth differentiation 15 (GDF15) has recently become a potential biomarker correlated with severity. Thus, this critical review aimed to determine association between GDF15 COVID-19. The perfect function remains not well-recognized; nevertheless, it plays vital role controlling cell growth, apoptosis inflammatory activation. Furthermore, may act as anti-inflammatory pro-inflammatory signaling diverse cardiovascular complications. release activated factors cytokines macrophage colony-stimulating (M-CSF), angiotensin II (AngII) p53. Therefore, higher expression might compensatory mechanism stabilize counteract dysregulated reactions. In conclusion, an cytokine that could be associated Increased against hyperinflammation exaggerated immune response Experimental, preclinical large-scale clinical studies warranted regard.

Language: Английский

---

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of…

Calcified Tissue International, Journal Year: 2023, Volume and Issue: 112(2), P. 197 - 217

Published: Jan. 12, 2023

Abstract In clinical trials, biochemical markers provide useful information on the drug’s mode of action, therapeutic response and side effect monitoring can act as surrogate endpoints. pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers measure in trials that could be used future practice. The objective current consensus paper a clear list musculoskeletal health aging recommended measured Phase II III evaluating new chemical entities treatment. A working group European Society Clinical Economic Aspects Osteoporosis, Osteoarthritis Musculoskeletal Diseases (ESCEO) proposed classifying into 2 series: status causal factors. For series 1, agreed 4 should assessed or (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N -terminal Type Procollagen Serum Creatinine Cystatin C Ratio – Sarcopenia Index). 2, 6 hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, cortisol, inflammatory C-reactive protein (CRP), interleukin-6 tumor necrosis factor- α ), IGF-I CRP). also optional may insights action therapies. Further research methods marker assays lead evolution these recommendations.

Language: Английский

---

Cytokines as Biomarkers for Evaluating Physical Exercise in Trained and Non-Trained Individuals: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11156 - 11156

Published: July 6, 2023

Physical activity and exercise training have numerous health benefits, including the prevention management of chronic diseases, improvement cardiovascular health, enhancement mental well-being. However, effectiveness programs can vary widely among individuals due to various factors, such as genetics, lifestyle, environment. Thus, identifying reliable biomarkers evaluate physical personalize is crucial. Cytokines are signaling molecules produced by immune cells that play a vital role in inflammation tissue repair. In recent years, there has been increasing interest potential use cytokines for evaluating effectiveness. This review article aims provide an overview cytokines, their biomarkers, methods measuring cytokine levels, factors affect levels. The also discusses benefits using monitoring muscle damage inflammation, personalized based on responses. We believe holds great promise optimizing improving overall outcomes.

Language: Английский

---

Overview of growth differentiation factor 15 in metabolic syndrome

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(9), P. 1157 - 1167

Published: March 29, 2023

Growth and differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. GDF15 has been linked with several metabolic syndrome pathologies such as obesity cardiovascular diseases. considered to be regulator, although its precise mechanisms action remain determined. Glial cell-derived neurotrophic family receptor alpha-like (GRAL), located in hindbrain, identified for signals through coreceptor tyrosine kinase (RET). Administration analogues preclinical studies using various animal models consistently shown induce weight loss reduction food intake. GDF15, therefore, represents an attractive target combat current global epidemic. In this article, we review knowledge on involvement syndrome.

Language: Английский

---

GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice

Nutrients, Journal Year: 2024, Volume and Issue: 16(5), P. 734 - 734

Published: March 4, 2024

In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as for growth differentiation 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction food intake body weight. is a cell stress cytokine widespread pleiotropic effects, which both seem to be contrast reported highly specialized localization its receptor. This discrepancy prompts us re-evaluate pattern GFRAL brain peripheral tissues mice. this detailed immunohistochemical study, we provide evidence more distribution Apart from AP/NTS region, GFRAL-immunoreactivity was found prefrontal cortex, hippocampus, arcuatus including liver, small intestine, fat, kidney muscle tissues. expression, not taken into consideration so far, may explain multiple GDF-15 that are yet assigned GFRAL. Furthermore, our results could relevant development novel pharmacological therapies physical mental disorders related image intake, such eating disorders, cachexia obesity.

Language: Английский

---