Targeting the “hallmarks of aging” to slow aging and treat age-related disease: fact or fiction?

Molecular Psychiatry, Год журнала: 2022, Номер 28(1), С. 242 - 255

Опубликована: Июль 15, 2022

Aging is a major risk factor for number of chronic diseases, including neurodegenerative and cerebrovascular disorders. processes have therefore been discussed as potential targets the development novel broadly effective preventatives or therapeutics age-related those affecting brain. Mechanisms thought to contribute aging summarized under term "hallmarks aging" include loss proteostasis, mitochondrial dysfunction, altered nutrient sensing, telomere attrition, genomic instability, cellular senescence, stem cell exhaustion, epigenetic alterations intercellular communication. We here examine key claims about aging". Our analysis reveals important weaknesses that preclude strong definitive conclusions concerning possible role these in shaping organismal rate. Significant ambiguity arises from overreliance on lifespan proxy marker aging, use models with unclear relevance study designs do not allow properly estimate intervention effects also discuss future research directions should be taken clarify if what extent putative regulators fact interact aging. These multidimensional analytical frameworks well facilitate proper assessment

Язык: Английский

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Ovarian aging in humans: potential strategies for extending reproductive lifespan

GeroScience, Год журнала: 2023, Номер 45(4), С. 2121 - 2133

Опубликована: Март 13, 2023

Язык: Английский

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An organismal understanding of C. elegans innate immune responses, from pathogen recognition to multigenerational resistance

Seminars in Cell and Developmental Biology, Год журнала: 2023, Номер 154, С. 77 - 84

Опубликована: Март 23, 2023

The nematode Caenorhabditis elegans has been a model for studying infection since the early 2000s and many major discoveries have made regarding its innate immune responses. C. found to utilize some key conserved aspects of responses signaling, but new interesting features immunity also discovered in organism that might broader implications higher eukaryotes such as mammals. Some distinctive involve mechanisms this bacterivore uses detect mount specific different pathogens, despite lacking putative orthologs important components, including cellular immunity, inflammasome, complement, or melanization. Even when known factors exist, there appears be an absence canonical functions, most notably lack pattern recognition by sole Toll-like receptor. Instead, recent research suggests senses pathogens through contextual information, unique products produced pathogen infection-induced disruption host physiology, similar proposed detection patterns pathogenesis mammalian systems. Interestingly, can transfer information past their progeny, providing robust protection offspring face persisting part RNAi pathway well potential remain elucidated. Altogether, these strategies employed share conceptual with vertebrate adaptive animal differentiate microbial features, propagate form memory offspring.

Язык: Английский

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BMP signaling to pharyngeal muscle in the C. elegans response to a bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping

Molecular Biology of the Cell, Год журнала: 2024, Номер 35(4)

Опубликована: Фев. 21, 2024

Host response to pathogens recruits multiple tissues in part through conserved cell signaling pathways. In

Язык: Английский

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Genetic variation in age-dependent attractiveness in a fish with a mixed mating system

Biology Letters, Год журнала: 2025, Номер 21(1)

Опубликована: Янв. 1, 2025

Reproductive senescence is common across taxa and females often show a predictable decline in fecundity after maturity. Attending to these age-dependent cues could help males make optimal mate choice decisions. Here, we examined reproductive male the androdioecious mangrove rivulus ( Kryptolebias marmoratus ), where self-fertilizing hermaphrodites exist with rare males. Hermaphrodites showed strong as they aged genetic lineages varied their at both young old ages. Surprisingly, when given simultaneous between genetically identical hermaphrodites, did not simply prefer younger hermaphrodites. Instead, preference for versus older partners depended on lineage of partners, resulting genotype × age interaction. For some lineages, were more attractive younger, but other older. Our results suggest that identity partner key how weigh changes are able assess variation attractiveness over partner’s lifespan. Exploring gamete viability outcrossing affected by us further understand preferences.

Язык: Английский

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C. elegans ageing is accelerated by a self-destructive reproductive programme

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 20, 2023

In post-reproductive C. elegans, destructive somatic biomass repurposing supports production of yolk which, it was recently shown, is vented and can serve as a foodstuff for larval progeny. This reminiscent the suicidal reproductive effort (reproductive death) typical semelparous organisms such Pacific salmon. To explore possibility that elegans exhibits death, we have compared sibling species pairs genera Caenorhabditis Pristionchus with hermaphrodites females. We report venting constitutive, early pathology involving major anatomical changes occur only in hermaphrodites, which are also shorter lived. Moreover, does germline removal suppress senescent markedly increase lifespan. consistent hypothesis exhibit death suppressed by ablation. If correct, this would imply difference ageing process between most higher organisms, potentially explain exceptional plasticity ageing.

Язык: Английский

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C. elegans as a model organism to study female reproductive health

Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology, Год журнала: 2022, Номер 266, С. 111152 - 111152

Опубликована: Янв. 13, 2022

Язык: Английский

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Considering Caenorhabditis elegans Aging on a Temporal and Tissue Scale: The Case of Insulin/IGF-1 Signaling

Cells, Год журнала: 2024, Номер 13(3), С. 288 - 288

Опубликована: Фев. 5, 2024

The aging process is inherently complex, involving multiple mechanisms that interact at different biological scales. nematode

Язык: Английский

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A Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in Caenorhabditis elegans

Genes to Cells, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 1, 2025

ABSTRACT During embryogenesis, organisms function as a robust system that ensures uniformity within individuals, but they lose robustness and develop variations at advanced ages. However, when how this remains largely elusive. Here, we identified sharp transition from interindividual to diversity in the appearance transcriptional features of age‐matched Caenorhabditis elegans midlife. Convolutional neural network analysis individual alterations revealed occurs midlife, which coincides with cessation egg‐laying activity increased motility defects. This period represents young state, marked by shared homogeneous among same‐age old individuals. Transcriptional coherence individuals shows essentially same transition, coinciding features. These findings provide new framework for understanding aging trajectory C. , demonstrating occurrence loss control over homeostasis

Язык: Английский

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Synthetic Cathinones Induce Developmental Arrest, Reduce Reproductive Capacity, and Shorten Lifespan in the C. elegans Model

Journal of Xenobiotics, Год журнала: 2025, Номер 15(1), С. 33 - 33

Опубликована: Фев. 18, 2025

Drug abuse presents a significant global health challenge as the illicit drug market progresses from classic drugs to growing prevalence of New Psychoactive Substances (NPS), particularly synthetic cathinones, which, although illegal, are often falsely marketed safe and legal alternatives. The rapid increase in use these complicates assessment their safety effects on human health. However, they pose unique toxicological concerns that remain largely uncharacterized. This study investigated toxic three namely, methylone, pentedrone, 4-methylethcathinone (4-MEC), using model organism C. elegans. We assessed impact substances animal survival, development, reproductive behavior, longevity. Our results showed short-term exposure (24 h) concentrations 5.0 mM or higher significantly reduced survival rates, while prolonged (72 led more pronounced toxicity, reducing rates at low 1.0 mM. Moreover, sublethal resulted developmental arrest. Additionally, pentedrone impaired capacity, 4-MEC shortened elegans lifespan. These findings highlight urgent need for further investigation into implications cathinone through vivo models continues rise.

Язык: Английский

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