Proteolysis dysfunction in the process of aging and age-related diseases DOI Creative Commons
Natalia Frankowska, Katarzyna Lisowska, Jacek M. Witkowski

et al.

Frontiers in Aging, Journal Year: 2022, Volume and Issue: 3

Published: July 22, 2022

In this review, we discuss in detail the most relevant proteolytic systems that together with chaperones contribute to creating proteostasis network is kept dynamic balance maintain overall functionality of cellular proteomes. Data accumulated over decades demonstrate effectiveness elements declines age. scenario, failure degrade misfolded or faulty proteins increases risk protein aggregation, chronic inflammation, and development age-related diseases. This especially important context aging-related modification functions immune system.

Language: Английский

Inflammaging and Osteoarthritis DOI
Francesca Motta,

Elisa Barone,

Antonio Sica

et al.

Clinical Reviews in Allergy & Immunology, Journal Year: 2022, Volume and Issue: 64(2), P. 222 - 238

Published: June 18, 2022

Language: Английский

Citations

205

Mucosal immune responses to infection and vaccination in the respiratory tract DOI Creative Commons
Robert C. Mettelman, E. Kaitlynn Allen, Paul G. Thomas

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(5), P. 749 - 780

Published: May 1, 2022

Language: Английский

Citations

155

Chronic inflammation and the hallmarks of aging DOI Creative Commons
Jordan J. Baechle, Nan Chen, Priya Makhijani

et al.

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

Citations

153

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations DOI Creative Commons
Gérald J. Prud’homme, Mervé Kurt, Qinghua Wang

et al.

Frontiers in Aging, Journal Year: 2022, Volume and Issue: 3

Published: July 12, 2022

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These have shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of opposite effects, extending lifespan. In humans, levels decline with age, chronic kidney diabetes, Alzheimer's disease other conditions. Low correlate an increase the death rate from all causes. acts either obligate coreceptor fibroblast growth factor 23 (FGF23), or soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced kidneys, but also brain, pancreas tissues. On tubular-cell membranes, it associates FGF receptors to bind FGF23. Produced bones, FGF23 regulates excretion phosphate (phosphaturic effect) vitamin D metabolism. Lack results hyperphosphatemia hypervitaminosis D. With human function often deteriorates, lowering levels. This appears promote age-related pathology. Remarkably, inhibits four pathways that been linked aging various ways: Transforming β (TGF-β), insulin-like 1 (IGF-1), Wnt NF-κB. can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis neoplasia. Furthermore, increases cell-protective antioxidant enzymes through Nrf2 FoxO. accord, preclinical therapy ameliorated renal, cardiovascular, diabetes-related neurodegenerative diseases, well cancer. s-Klotho injection was effective, requires further investigation. Several drugs enhance circulating levels, some cross blood-brain barrier potentially act brain. clinical trials, increased noted renin-angiotensin system inhibitors (losartan, valsartan), statin (fluvastatin), mTOR (rapamycin, everolimus), pentoxifylline. work, antidiabetic (metformin, GLP-1-based, GABA, PPAR-γ agonists) enhanced Klotho. traditional medicines and/or nutraceuticals rodents, including astaxanthin, curcumin, ginseng, ligustilide resveratrol. Notably, exercise sport activity review addresses molecular, physiological therapeutic aspects

Language: Английский

Citations

124

Aging and chronic inflammation: highlights from a multidisciplinary workshop DOI Creative Commons
Danay Saavedra, Ana Laura Añé-Kourí, Nir Barzilai

et al.

Immunity & Ageing, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 8, 2023

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. entails the immune system characterized by decrease thymic output naïve lymphocytes, an accumulated chronic antigenic stress notably caused infections such as cytomegalovirus (CMV), cell senescence with acquisition inflammatory senescence-associated secretory phenotype (SASP). For this reason, due to SASP originating from other tissues, aging commonly accompanied low-grade inflammation, termed "inflammaging". After decades accumulating evidence regarding age-related processes domain now appears mature enough allow integrative reinterpretation old data. Here, we provide overview topics discussed recent workshop "Aging Chronic Inflammation" which many major players field contributed. We highlight advances systematic measurement interpretation biological markers aging, well their implications for human health longevity interventions that can be envisaged maintain or improve function older people.

Language: Английский

Citations

80

Persistent serum protein signatures define an inflammatory subcategory of long COVID DOI Creative Commons
Aarthi Talla, Suhas Vasaikar, Gregory L. Szeto

et al.

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

Published: June 9, 2023

Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute infection. The aetiologies may include persistent inflammation, unresolved tissue damage delayed clearance viral protein RNA, but the biological differences they represent are not fully understood. Here we evaluate serum proteome in samples, longitudinally collected from 55 PASC individuals with lasting ≥60 days after onset infection, comparison to samples symptomatically recovered infected and uninfected individuals. Our analysis indicates heterogeneity identified subsets distinct signatures inflammation. Type II interferon signaling canonical NF-κB (particularly associated TNF), appear be most differentially enriched pathways, distinguishing group patients characterized also by neutrophil activation signature. These findings help clarify diversity within PASC, identify participants molecular evidence highlight dominant pathways have diagnostic therapeutic relevance, including panel propose as having utility differentiating inflammatory non-inflammatory PASC.

Language: Английский

Citations

80

Nutrition, Immunosenescence, and Infectious Disease: An Overview of the Scientific Evidence on Micronutrients and on Modulation of the Gut Microbiota DOI Creative Commons
Philip C. Calder, Edwin F. Ortega,

Simin Nikbin Meydani

et al.

Advances in Nutrition, Journal Year: 2022, Volume and Issue: 13(5), P. S1 - S26

Published: May 6, 2022

The immune system is key to host defense against pathogenic organisms. Aging associated with changes in the system, a decline protective components (immunosenescence), increasing susceptibility infectious disease, and chronic elevation low-grade inflammation (inflammaging), risk of multiple noncommunicable diseases. Nutrition determinant cell function gut microbiota. In turn, microbiota shapes controls inflammatory responses. Many older people show Age-related competence, inflammation, dysbiosis may be interlinked relate, at least part, age-related nutrition. A number micronutrients (vitamins C, D, E zinc selenium) play roles supporting many types. Some trials report that providing these as individual supplements can reverse deficits and/or those insufficient intakes. There inconsistent evidence this will reduce or severity infections including respiratory infections. Probiotic, prebiotic, synbiotic strategies modulate microbiota, especially by promoting colonization lactobacilli bifidobacteria, have been demonstrated some biomarkers and, cases, gastrointestinal infections, although, again, inconsistent. Further research well-designed well-powered at-risk populations required more certain about role modify microbiota-host relationship protecting infection, infection.

Language: Английский

Citations

77

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation DOI Creative Commons
Carlos A. Labarrere, Ghassan S. Kassab

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

Published: Nov. 1, 2022

Many local and systemic diseases especially that are leading causes of death globally like chronic obstructive pulmonary disease, atherosclerosis with ischemic heart disease stroke, cancer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing 19 (COVID-19), involve both, (1) oxidative stress excessive production reactive oxygen species (ROS) lower glutathione (GSH) levels, (2) inflammation. The GSH tripeptide (γ- L-glutamyl-L-cysteinyl-glycine), the most abundant water-soluble non-protein thiol in cell (1–10 mM) is fundamental for life by (a) sustaining adequate redox signaling needed to maintain physiologic levels control processes, (b) limiting tissue damage. activity facilitated activation Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related (Nrf2)-antioxidant response element (ARE) regulator pathway, releasing Nrf2 regulates expression genes controlling antioxidant, inflammatory immune system responses. exists thiol-reduced (>98% total GSH) disulfide-oxidized (GSSG) forms, concentrations GSSG their molar ratio indicators functionality cell. depletion may play a central role COVID-19 pathophysiology, host severity mortality. Therapies enhancing could become cornerstone reduce fatal outcomes increasing prevent subdue these diseases. value makes paramount research field biology medicine be key against inflammation SARS-CoV-2 infection disease. In this review, we emphasize on as risk (ischemic stroke), importance antioxidants (3) significance counteract persistent damaging inflammation, inflammaging early (premature) associated damage caused lack antioxidant defenses younger individuals, (4) new therapies include restoration.

Language: Английский

Citations

72

Oxidative stress, inflammation and hormesis: The role of dietary and lifestyle modifications on aging DOI
Vinita Sharma, Mohammad Murtaza Mehdi

Neurochemistry International, Journal Year: 2023, Volume and Issue: 164, P. 105490 - 105490

Published: Jan. 24, 2023

Language: Английский

Citations

59

Chronic effects of inflammation on tauopathies DOI

Connor Langworth-Green,

Saisha Patel,

Zane Jaunmuktane

et al.

The Lancet Neurology, Journal Year: 2023, Volume and Issue: 22(5), P. 430 - 442

Published: April 13, 2023

Language: Английский

Citations

46