Mitochondrial decline in the ageing old world primate retina: Little evidence for difference between the centre and periphery DOI Creative Commons
Jaimie Hoh Kam,

Harpreet Shinhmar,

Michael B. Powner

et al.

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(5), P. e0273882 - e0273882

Published: May 2, 2023

Mitochondrial decline is a key feature of ageing. The retina has more mitochondria than any other tissue and ages rapidly. To understand human retinal ageing it critical to examine old world primates that have similar visual systems humans, do so across central peripheral regions, as there evidence for early decline. Hence, we mitochondrial metrics in young Macaca fascicularis retinae. In spite reduced ATP with age, primate complex activity did not But membrane potentials were significantly, concomitantly, permeability increased. marker Tom20 declined consistent number, while VDAC, voltage dependent anion channel diffusion pore associated apoptosis increased significantly. these clear age-related changes, was almost no regional differences between the centre periphery metrics. Primate cones die but many showed marked structural vacuous spaces proximal inner segments normally occupied by endoplasmic reticulum (ER), regulate autophagy. cones, ER displaced nucleus transposed outer limiting could become embedded populations. These data are significant changes provide little if aged suffer those periphery.

Language: Английский

Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction DOI
Anna S. Monzel, José Antonio Enrı́quez, Martin Picard

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(4), P. 546 - 562

Published: April 26, 2023

Language: Английский

Citations

295
The evolutionary history and spectral tuning of vertebrate visual opsins DOI Creative Commons
Joanna F. D. Hagen, Natalie S. Roberts, Robert J. Johnston

et al.

Developmental Biology, Journal Year: 2022, Volume and Issue: 493, P. 40 - 66

Published: Nov. 9, 2022

Language: Английский

Citations

42
There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines DOI Creative Commons

Joshua Bongard,

Michael Levin

Biomimetics, Journal Year: 2023, Volume and Issue: 8(1), P. 110 - 110

Published: March 8, 2023

The applicability of computational models to the biological world is an active topic debate. We argue that a useful path forward results from abandoning hard boundaries between categories and adopting observer-dependent, pragmatic view. Such view dissolves contingent dichotomies driven by human cognitive biases (e.g., tendency oversimplify) prior technological limitations in favor more continuous view, necessitated study evolution, developmental biology, intelligent machines. Form function are tightly entwined nature, some cases, robotics as well. Thus, efforts re-shape living systems for biomedical or bioengineering purposes require prediction control their at multiple scales. This challenging many reasons, one which perform functions same place time. refer this “polycomputing”—the ability substrate simultaneously compute different things, make those available observers. important way things kind computer, but not familiar, linear, deterministic kind; rather, computers broad sense materials, reported rapidly growing physical computing literature. observer-centered framework computations performed evolved designed will improve understanding mesoscale events, it has already done quantum relativistic To develop our how life performs polycomputing, can be convinced alter functions, we first create technologies polycompute learn functions. Here, review examples idea overloading on hardware design principle helps understand build both systems. Learning hack existing polycomputing substrates, well evolve new ones, have massive impacts regenerative medicine, robotics, computer engineering.

Language: Английский

Citations

39
Mechanisms of Mitochondrial Malfunction in Alzheimer’s Disease: New Therapeutic Hope DOI Open Access
Showkat Ul Nabi, Andleeb Khan, Ehraz Mehmood Siddiqui

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 28

Published: May 14, 2022

Mitochondria play a critical role in neuron viability or death as it regulates energy metabolism and cell pathways. They are essential for cellular metabolism, reactive oxygen species production, apoptosis, Ca++ homeostasis, aging, regeneration. Mitophagy mitochondrial dynamics thus processes the quality control of mitochondria. Improvements several fundamental features biology susceptible neurons AD brains putative underlying mechanisms such changes have made significant progress. AD’s etiology has been reported by malfunction oxidative damage. According to recent articles, continual fusion fission balance mitochondria is vital their normal function maintenance. As result, shape inextricably linked. This study examines evidence suggesting that dysfunction plays early impact on pathology. Furthermore, roles discussed with link between autophagy also explored. In addition, research mitophagy this review. It goes into how these flaws affect control. advanced therapy techniques lifestyle adjustments lead improved management demonstrated, hence improving conditions contribute AD.

Language: Английский

Citations

34
Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging DOI Creative Commons
Qixiang Gui, Neng Ding,

Zuochao Yao

et al.

Precision Clinical Medicine, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 8, 2024

Abstract Owing to its constant exposure the external environment and various stimuli, skin ranks among organs most vulnerable manifestations of aging. Preventing delaying aging has become one prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent derived from mesoderm with high self-renewal ability multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) nanoscale biological that facilitate intercellular communication regulate behavior. Recent studies have shown MSC-EVs potential applications anti-aging therapy due their anti-inflammatory, anti-oxidative stress, wound healing promoting abilities. This review presents latest progress It mainly includes proliferation migration keratinocytes fibroblasts, reducing expression matrix metalloproteinases, resisting oxidative regulating inflammation. We then briefly discuss recently discovered treatment methods field anti-aging. Moreover, advantages limitations EV-based treatments also presented.

Language: Английский

Citations

7
Epigenome–metabolism nexus in the retina: implications for aging and disease DOI Creative Commons
Anupam K. Mondal, Mohita Gaur, Jayshree Advani

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Intimate links between epigenome modifications and metabolites allude to a crucial role of cellular metabolism in transcriptional regulation. Retina, being highly metabolic tissue, adapts by integrating inputs from genetic, epigenetic, extracellular signals. Precise global epigenomic signatures guide development homeostasis the intricate retinal structure function. Epigenomic realignment are hallmarks aging highlight link epigenome–metabolism nexus with aging-associated multifactorial traits affecting retina, including age-related macular degeneration glaucoma. Here, we focus on emerging principles control gene regulation, emphasis their contribution human disease. In addition, discuss potential mitigation strategies involving lifestyle changes that target epigenome-metabolome relationship for maintaining

Language: Английский

Citations

5
Fullerol rescues the light-induced retinal damage by modulating Müller glia cell fate DOI Creative Commons

Zhe Cha,

Zhiyuan Yin,

A Luodan

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102911 - 102911

Published: Oct. 5, 2023

Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers have been proven protect against photo-damaged degeneration. Fullerol, potent antioxidant, has the potential ultraviolet-B (UVB)-induced cornea injury by activating endogenous stem cells. However, its effects on cell fate determination of Müller glia (MG) between gliosis de-differentiation remain unclear. Therefore, we established MG lineage-tracing mouse model light-induced examine therapeutic fullerol. Fullerol exhibited superior protection compared glutathione (GSH) reduced oxidative levels, inhibited suppressing TGF-β pathway, enhanced RNA sequencing revealed that transcription candidate pathways, including Nrf2 Wnt10a were involved fullerol-induced neuroprotection. Fullerol-mediated transcriptional changes validated qPCR, Western blotting, immunostaining using retinas human-derived lines MIO-M1 cells, confirming fullerol possibly modulated Nrf2, Wnt10a, pathways MG, which suppressed promoted degeneration, indicating treating diseases.

Language: Английский

Citations

12
Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status DOI Creative Commons
Aidan Anderson, Nada Alfahad,

Dulani Wimalachandra

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 6, 2024

The recovery of mitochondrial quality control (MQC) may bring innovative solutions for neuroprotection, while imposing a significant challenge given the need holistic approaches to restore dynamics (fusion/fission) and turnover (mitophagy biogenesis). In diabetic retinopathy, this is compounded by our lack understanding human retinal neurodegeneration, but also how MQC processes interact during disease progression. Here, we show that mitochondria hyperfusion characteristic neurodegeneration in murine diabetes, blunting homeostatic causing metabolic neuro-inflammatory stress. By mimicking remodelling vitro, ascertain N6-furfuryladenosine enhances bioenergetics relaxing controlled fashion. Oral administration mouse retina (Ins2Akita males), improving clinical correlates conferring neuroprotection regardless glycaemic status. Our findings provide translational insights through MQC.

Language: Английский

Citations

4
Retinopathy of prematurity: Metabolic risk factors DOI Creative Commons
Zhongjie Fu, Anders K. Nilsson, Ann Hellström

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Nov. 16, 2022

At preterm birth, the retina is incompletely vascularized. Retinopathy of prematurity (ROP) initiated by postnatal suppression physiological retinal vascular development that would normally occur in utero. As neural slowly matures, increasing metabolic demand including peripheral avascular retina, leads to signals for compensatory but pathological neovascularization. Currently, only late neovascular ROP treated. could be prevented promoting normal growth. Early perinatal dysregulation a strong understudied risk factor and other long-term sequelae birth. We will discuss oxygen needs current treatments, potential interventions promote vessel growth control hyperglycemia, dyslipidemia hyperoxia-induced alterations. supplementation missing nutrients factors supplemental promotes development. knowledge gap metabolism after

Language: Английский

Citations

18
Pulmonary surfactant and COVID-19: A new synthesis DOI Creative Commons
Barry W. Ninham, Brandon Reines, Matthew Battye

et al.

QRB Discovery, Journal Year: 2022, Volume and Issue: 3

Published: Jan. 1, 2022

COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2; as these produce pulmonary surfactant (PS), possibility that insufficient PS plays a role in has been raised. However, opposite predicted high alveolar surface tension is found many early patients: paradoxically normal lung volumes and compliance occur, profound hypoxemia. That 'COVID anomaly' was quickly rationalised by invoking vascular mechanisms-mainly because surprisingly preserved hypoxemic cases. quick rejection damage only occurred actual mechanism gas exchange long presumed be non-problematic, due diffusion through surface. On contrary, we provide physical chemical evidence occurs an process expansion contraction three-dimensional structures its associated proteins. This view explains anomalous observations from level cryo-TEM whole individuals. It encompasses results premature infants deepest diving seals. Once understood, COVID anomaly dissolves straightforwardly explained covert viral 3D structure PS, direct treatment implications. As natural experiment, SARS-CoV-2 virus itself helped us simplify clarify not nature dyspnea relationship compliance, but also fine detail including such features water channels which had heretofore entirely unexpected.For time, physical, colloid chemistry have intersected physiology cell biology much might hoped. The reasons starting become clear. discipline suffered serious unrecognised omissions rendered it ineffective. These foundational defects included omission specific ion molecular forces hydration effects. lacked predictive theory self-assembly lipids Worse, omitted any for dissolved gases, O2, N2, CO2, their existence stable nanobubbles above physiological salt concentration. Recent developments gone some way explaining foam-like function. delivers O2/N2 nanobubbles, efflux H2O at Knowledge allows explanation corona entry, differences infectivity different variants. CO2 resulting metabolism passing frit provided glycocalyx venous tissue, forms previously unexplained foam endothelial layer. turn out lethal viruses, providing plausible origin 'Long COVID'. Circulating 0.17 M drive various enzyme-like activities reactions. Awareness microstructure Pulmonary Surfactant (O2/N2) integral respiratory circulatory provides new insights other pathogen activity.

Language: Английский

Citations

16