ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases

Oxidative Medicine and Cellular Longevity, Год журнала: 2016, Номер 2016(1)

Опубликована: Янв. 1, 2016

The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression metabolic control, rate has been associated with production of high levels Reactive Oxygen Species (ROS) and/or Nitrosative (RNS). Specific increases ROS level have demonstrated as potentially critical for induction maintenance cell senescence process. Causal connection between ROS, aging, age‐related pathologies, is studied intensely. Senescent cells proposed a target interventions delay related diseases or improve treatment. Therapeutic towards senescent might allow restoring health curing that share basal processes, rather than each disease separate symptomatic way. Here, we review observations on ability inducing through novel mechanisms underpin processes. Particular emphasis addressed involvement epigenetic regulation aim individuate specific pathways, which promote healthy lifespan aging.

Язык: Английский

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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(18), С. 4472 - 4472

Опубликована: Сен. 10, 2019

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed the elderly population. Inflammaging associated over-abundance reactive oxygen species cell, which can lead to oxidation and damage cellular components, increased inflammation, activation cell death pathways. This review focuses on inflammaging its contribution various age-related diseases such cardiovascular disease, cancer, neurodegenerative diseases, obstructive pulmonary diabetes, rheumatoid arthritis. Recently published mechanistic details roles will also be discussed. Advancements potential treatments ameliorate oxidative stress, consequently, reduce morbidity explored.

Язык: Английский

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Hallmarks of senescence and aging

Biochemia Medica, Год журнала: 2019, Номер 29(3), С. 483 - 497

Опубликована: Июль 17, 2019

The complex process of biological aging, as an intrinsic feature living beings, is the result genetic and, to a greater extent, environmental factors and time. For many changes taking place in body during three are important: inflammation, immune aging senescence (cellular aging). Senescence irreversible form long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress damage. purpose this cell-cycles arrest limit proliferation damaged cells, eliminate accumulated harmful disable potential malignant cell transformation. As age does not have be accordance with chronological age, it important find specific hallmarks biomarkers that could objectively determine rate person. These might valuable measure physiological, i.e. age. Biomarkers should meet several criteria. example, they predict monitor basic underlies process, able tested repeatedly without harming In addition, indicators processes, pathogenic processes pharmacological responses therapeutic intervention. It considered telomere length weak biomarker (with poor predictive accuracy), there currently no reliable meets all necessary

Язык: Английский

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Mitochondrial Dynamics in Stem Cells and Differentiation

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(12), С. 3893 - 3893

Опубликована: Дек. 5, 2018

Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is adenosine triphosphate (ATP) production; however, they additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, proliferation, differentiation, reprogramming, and aging. The mitochondrial morphology closely related to the functionality mitochondria. Normal dynamics critical for function, embryonic development, tissue formation. Thus, defects proteins control fusion fission can affect Here, we review processes various associated phenomena.

Язык: Английский

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Adrenal Aging and Its Implications on Stress Responsiveness in Humans

Frontiers in Endocrinology, Год журнала: 2019, Номер 10

Опубликована: Фев. 7, 2019

Normal aging results in subtle changes both ACTH and cortisol secretion. Most notable is the general increase mean daily serum levels elderly, without a noteworthy alteration normal circadian rhythm pattern. Glucocorticoid excess seen elderly population can have serious consequences structural functional integrity of various key areas brain, including hippocampus, amygdala, prefrontal cortex, with consequent impairment memory, cognitive function sleep cycles. The chronically elevated glucocorticoid also impinge on stress response leading to an impaired ability recover from stressful stimuli. In addition effects associated other age-related changes, loss muscle mass, hypertension, osteopenia, visceral obesity diabetes, among others. contrast levels, adrenocortical hormones, particularly aldosterone DHEA (the precursor androgens estrogens) show significant decreases elderly. underlying mechanisms for their decrease remain unclear. While adrenomedullary hormone, norephinephrine, shows plasma clearance, no observed epinephrine multiplicity complexity adrenal hormone throughout process, suggests that alterations cellular growth, differentiation, senescence specific gland must be considered.

Язык: Английский

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Effects of Aging in Dry Eye

International Ophthalmology Clinics, Год журнала: 2017, Номер 57(2), С. 47 - 64

Опубликована: Янв. 1, 2017

Introduction Tear dysfunction is one of the most common problems encountered by eye doctors. has a reported prevalence ranging from 2% to 14.2%.1–3 It been found increase with age fourth eighth decade life and more prevalent in women than men throughout this period.4,5 results disease or components lacrimal functional unit that consists tear producing glands their neural connections. Many patients over 40 have evidence meibomian gland (MGD) as an underlying cause, particularly unstable film, but normal production volume. This review will focus on epidemiological aspects aging, possible mechanisms for age-related dry discuss some potential therapies along lessons learned animal models aging. Aging Risk Factor Dry Eye Significant Large studies Women's Health Study Physician's noted increases every 5 years after 50, greater compared men.1,3–8 Age female sex be greatest risk factors eye. supported clinical findings decreased through sixth life.9,10 The corneal surface irregularity degrades visual function decreasing contrast sensitivity acuity.11,12 presence was significantly impact ability perform daily activities such reading, using computer driving.13 Using time trade-off techniques, Schiffman et al14 calculated severe had same quality-of-life moderate angina.15 With increasing aged population increased expectancy, it expected continue main reasons ophthalmologic visits.16 Therefore, better understanding specifically tailored specific are much needed. (LG) suffers Various histopathologic changes were observed human LG acinar atrophy; periacinar fibrosis; periductal interlobular ductal dilatation; proliferation; lymphocytic infiltration; fatty infiltration.17–20 Several differences exist between palpebral orbital lobes. Diffuse fibrosis diffuse atrophy lobes frequently men.20,21 Rodents used aging research suffer aging-related similar humans (see Rocha al).22–25 Age-related eyelid alterations include lid laxity, (MG) orifice metaplasia, decrease volume break-up eye.26–31 In young healthy eyelid, MG orifices located anterior mucocutaneous junction can identified Marx's line, physiological line staining diagnostic dyes, fluorescein, lissamine green, rose bengal. migrate anteriorly aging.32 androgen receptors respond stimulation31,33–37 MGD frequent women.28,29,38,39 may occur itself association aqueous-tear deficiency (ATD). inflammatory cytokine milieu both tears conjunctiva cells collected impression cytology different ATD.40–44 ATD significant goblet cell loss, expression interferon (IFN)-γ interleukin (IL)-17A controls, none aforementioned present patients.44 Another disorder conjunctivochalasis, condition where folds becomes redundant obstruct puncta cause ocular discomfort. often associated age45–48 discussed details companion article Gumus Pflugfelder. There still controversy if leads dry-eye totally mechanism per se.49 For example, factor loss remains controversial.23,50–54 becoming apparent autoimmune eye, inflammation complex immune response overtime profound (Fig. 1).22–25,28,51,55–58Figure 1: induces systemic also unit.Age-related Comorbidities Iatrogenic accompanied co-morbidities cardiovascular diseases, type 2 diabetes, depression, glaucoma, other diseases. Some these comorbidities themselves medications manage them, deleterious secondary effect surface. An example diabetes mellitus affects retina, nerves eye.59–61 alters homeostasis required control original morbidity drying effects. antihypertensive, antihistaminics antidepressants well-recognized classes drugs surface.3,5–8,56,62 complete list aggravate please refer Fraunfelder colleagues62,63 visit National Drug registry (www.eyedrugregistry.com/about.html). Patients incidence elderly patients, complain about irritation.64,65 Although direct compounds treat glaucoma cannot excluded, benzalkonium chloride, widely eyedrop preservative due its potent antibacterial action, recognized toxic Benzalkonium chloride enhances drug penetration, partially epithelial barrier breakage toxicity epithelium.65–68 Recent shown switching preservative-free solution improved related-symptoms no efficacy antiglaucoma drugs, promising relief great number eyedrops.69–71 Possible Mechanisms Leading All organisms start soon they born. celebrated milestones (ie, first baby steps words, definitive tooth, mustache shaving boys; child, etc.), decline health status vitality accompanies nuisance many. economical burden society caregivers expectancy well susceptibility cancer, autoimmunity, frailty. system undergoes named immunosenescence, characterized naive T cells, chronic inflammation, hyperimmunoglobulinemia, poor vaccines, infections.72–75 A typical feature chronic, low-grade status, inflammaging,76 general proinflammatory cytokines. Increased serum mediators Alzheimer disease, dementia, Parkinson diabetes.76–78 consequences survival reliable predictors mortality elderly.75 Other cellular/metabolic theories regarding oxidative stress, DNA damage, alteration repair, protein glycation, telomere shortening, proteasome name few.79,80 extensive body accumulated areas, precise mechanism(s) poorly understood. Every ages, not at rate; accompany pathologic person unique so own true inflammation. last 20 there shift paradigm, merely autoimmunity play important role. levels related IL-1β, IL-6, TNF-α, IL-17, IFN-γ fluid subjects.12,40,44,81–90 activation local environment another universal HLA-DR+ finding, which indicator therapeutic trials.81,91–100 features matrix metalloproteinases (MMPs), chemokines proteins involved squamous metaplasia epithelium, endoplasmic reticulum stress.12,81,83,85,96,97,101–117 acute exacerbations when performing driving, viewing video display long periods shopping stores high flow AC. live work controlled drafty and/or low humidity (desiccating stress) environmental conditions, irritation disease118–122 experience productivity quality life.123,124 Exposure desiccating conditions activate stress-sensing cells/pathways surface, stimulate synthesize secrete cytokines MMPs detected themselves.42,85 stress sensitize nociceptors changes, breakdown tight junctions resulting dysfunction, clinically uptake fluorescein. Calonge colleagues.125 Animal Models variety described study pathogenesis model uses combination humidity, pharmacological cholinergic blockade become standard field. 65 publications since description.126 recapitulates several inclusive epithelium.127–145 mostly inbred C57BL/6 mouse strain, while Balb/c mice slightly kinetics.143 valuable tool develop MGD, staining, conjunctival infiltration dacryoadenitis.23,146,147 Similarly desiccated Sjögren Syndrome (SS) MMP-9 T-cell IFN-γ, influx CD4+ CD8+ into LG,23 suggesting multiple inciting converge produce independent initiating factor. Inflammation denominator situations. Lessons Stern Pflugfelder.148 Pathogenic utilized summarized briefly next paragraphs. Female Sex Similar studies,4,149 disruption age-matched male mice, although density sexes.23 IL-17A mice. IL-17 stimulates -3 -9, break disrupt function.85,150–153 life7,14 vision, decreases sensitivity.12,13 We speculate bring clinic men, hormones influences excluded. Aged Cells Spontaneously Autoreactive SS subjects, stressed biopsies.154–159 mice.23 Furthermore, adoptive transfer induced donors, demonstrating participate eye.23,25 These indicate promotes generation autoreactive cells; however, unknown wells antigen. system, lack peripheral tolerance exposure antigen life's period maybe play. all three could acting synergistically. Interferon-γ Participates Goblet Cell Loss goblet-cell richest tissues body, just trailing intestinal tract. very sensitive besides mucins, implicated immunomodulation surface.160–163 Th-2 signature IL-13 role homeostasis.164,165 contrast, negatively cells.112,131,159,166 DS-induced aged-induced upregulation KO resistant aged-related loss.23,57,159 Regulatory Dysfunctional variation nonobese diabetic does Coursey al25 demonstrated dacryoadenitis NOD.B10.H2b frequency regulatory (Tregs) LG, despite pathology strain. agreement reports biopsies salivary Foxp3+ correlated disease.167,168 Despite being dysfunctional unable suppress effector vitro, murine Tregs do loose expression, acquire IL-17. regs effectors resulted higher keratoconjunctivitis scores effectors, vivo suppression acquisition phenotype.25 Oxidative Stress Impairs Secretion Reactive oxygen species generated metabolism must counteracted antioxidant defenses prevent damage lipids, DNA, mitochondria. Mice mitochondrial antioxidative pathways altered homeostasis, leading volume, staining.169–172 support studies, enzymes markers patients.108–111 Elevated concentration hexanoyl-lysine, lipid marker, confocal microscopy evaluating controls.108 unclear occurs consequence Deng al173 recently showed hyperosmolarity cultured cells. MGs Become Atrophic Histologic analysis eyelids many morphologic including cystic dilatation acini ducts, acini, thickening basement membrane, granulation tissue, lipogranulomatous inflammation.26 dropout cytokines, meibocyte differentiation.145,146,174,175 postulated stem within necessary duct keratinization, Keratin 10 nor SPRR1-a MG.146,175 elegant immunofluorescent computed tomography 3-dimensional reconstruction, keratinization further corroborating findings.146 Treatment only FDA-approved Cyclosporine, modulator, extensively forms eye.92,99,106,117,176–179 Lifitegrast, novel inhibitor lymphocyte function-associated antigen-1 (LFA-1) migration vessels, received approval signs symptoms July 2016. Results phase 3 trials results.180–182 reviews current see published reviews.183–185 new reviewed nonpharmacological approach improve use supplements. Polyunsaturated acids omega-6 (linolenic acid) omega-3 (α-linolenic gained popularity oral supplements dendritic cells.95,186–190 holistic aging-dry proposed involves calorie restriction (CR) supplementation vitamins antioxidants.191 CR without malnutrition emerged 21st century strategy 1935 McCay al,192 interest prolonged span, tumors rodents.193–196 duplicated nonhuman primates,197,198 generating scientific community intervention. massive then, metabolic, hormonal molecular changes. detailed NIH-sponsored CALERIE (comprehensive assessment long-term effects reducing intake energy) trial humans, Most al.199 ophthalmology, substantially submandibular prone mice.200 TNF-α IL-6 TGF-β1 noted.200 rats, 6 months secretion, morphology oxidation 8-hydroxy-2 deoxyguanosine (8-OHdG) 4-hydroxynonenal relates stress.201 Conclusions intensive research, nature elusive. Not rate. However, biochemical, molecular, interacting. participates Understanding enable early interventions end-stage organ disease.

Язык: Английский

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Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing

Ageing Research Reviews, Год журнала: 2016, Номер 33, С. 76 - 88

Опубликована: Май 12, 2016

Язык: Английский

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Anti-Aging Effect of Chitosan Oligosaccharide on d-Galactose-Induced Subacute Aging in Mice

Marine Drugs, Год журнала: 2018, Номер 16(6), С. 181 - 181

Опубликована: Май 24, 2018

Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate possible anti-aging effect COS on aging model mouse induced by d-galactose (d-gal) explore underlying mechanism. In experiment, 48 male Kunming mice (KM mice) were randomly divided into normal group, positive low-medium-high dose groups (300, 600, 1200 mg/kg/day). results showed that COS, intragastric gavage after subcutaneous injection d-gal (250 mg/kg/day) neck consecutively for eight weeks, gradually recovered body weight, activity daily living, organ indices mice, as well effectively ameliorated histological deterioration liver kidney in triggered d-gal. To be specific, obviously improved activities enzymes KM including catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), decreased malondialdehyde (MDA) levels when compared those group mice. Furthermore, not only elevated diminished serum immunoglobulin G (IgG) IgM d-gal, but also significantly inhibited d-gal-caused upregulation alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) creatinine (CREA) group. These demonstrate has an obvious d-gal-induced subacute mechanism which, some extent, associated enhancing defenses, reducing oxidative stress, improving immune function

Язык: Английский

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Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

Nutrients, Год журнала: 2018, Номер 10(11), С. 1741 - 1741

Опубликована: Ноя. 12, 2018

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin type 1 receptor (AT1R) axis, plays an important role in aging process of kidney, through increased tissue reactive oxygen species production and progressively oxidative stress. In contrast, 1-7 1-7)/Mas (MasR) which counteracts effects Ang II, is protective for end-organ damage. To evaluate ability resveratrol (RSV) to modulate RAS kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or containing resveratrol, six months. Renal expressions components, as well pro- antioxidant enzymes, measured kidneys isolated histopathology. Resveratrol-treated demonstrated better renal function reduced albuminuria, with improved histologic findings. Resveratrol suppressed II/AT1R axis enhanced AT2R/Ang 1-7/MasR axis. Additionally, expression nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, fibronectin was decreased, while endothelial nitric oxide synthase superoxide dismutase 2 by treatment. These findings demonstrate exerts on reducing stress, inflammation, fibrosis, suppression MasR activation.

Язык: Английский

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The Ecology of Freshwater Planarians

Methods in molecular biology, Год журнала: 2018, Номер unknown, С. 173 - 205

Опубликована: Янв. 1, 2018

Язык: Английский

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