Intimate Relations—Mitochondria and Ageing

Webb, M.; Sideris, Dionisia P.

doi:10.3390/ijms21207580

Cited by 20 publications

(10 citation statements)

References 399 publications

(430 reference statements)

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“…Even if each of these assertions is sustained by experimental evidence, there are still several controversies and the cause–effect relationships among these events are still partially obscure. The complexity of biochemical, genetic, and regulatory systems and their inter-relationships are still not fully understood and often a single linear cause to effect relationship cannot be established [ 402 ]. Barja [ 403 ] however proposes that aging is the result of several effectors, i.e., mtROS production, lipid unsaturation, autophagy, mitochondrial DNA repair and putative other events such as apoptosis, proteostasis, or telomere shortening, already considered by different classic theories of aging.…”

Section: Physiological and Pathological Implicationsmentioning

confidence: 99%

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Nesci

Trombetti

Pagliarani

et al. 2021

Life

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Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

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Section: Physiological and Pathological Implicationsmentioning

confidence: 99%

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Nesci

Trombetti

Pagliarani

et al. 2021

Life

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“…The decrease of nail melatonin content observed with age reinforces the interest of using melatonin as aging biomarker [ 19 , 43 ] and opens the possibility of using nail melatonin content as ageing biomarker or even for the evaluation of anti-ageing therapies. In order to confirm that point, a correlation between nail melatonin content and common ageing biomarkers (oxidative stress, RedOx status, mitochondria activity, peroxisome activity, telomere length) [ 44 , 45 , 46 ] should be established. Additionally, the confirmation of these results by the analysis of a larger set of samples is advised in order to strengthen the applicability of the nail melatonin content as aging biomarker.…”

Section: Discussionmentioning

confidence: 99%

Nail Melatonin Content: A Suitable Non-Invasive Marker of Melatonin Production

Gómez-Gómez

Montero-San-Martin

Haro

et al. 2021

IJMS

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Melatonin plays multiple physiological roles in the human body. Evaluation of melatonin production by the determination of urinary 6-sulfatoxymelatonin in 24-h samples has important drawbacks which hinder the successful evaluation of melatonin production in large cohorts. Here, we evaluated the potential of nail analysis for estimating melatonin production. Firstly, mass spectrometry methodology for the determination of melatonin in nails was optimized and successfully validated. The method was found to be linear in the range 6.5–830 fg/mg with intraday and interday accuracy in the range 100–104 %, precision below 15 % and a LOD of 3.5 fg/mg. Secondly, nail melatonin concentrations from 84 volunteers (age 5–96) were determined. The expected correlation between melatonin and age was obtained (correlation coefficient −0.615; p < 0.001). Additionally, we showed that fingernails are preferable to toenails to determine nail melatonin content. Finally, fingernails collected for 180 days after melatonin administration (two volunteers, 1.9 mg/night during 5 days) were analyzed. Nail melatonin concentrations immediately rose after administration and went back to pre-administration values after ≈100 days in both volunteers. Our results suggest that melatonin determination in nails is a suitable non-invasive tool for the estimation of global melatonin production. Due to the easy collection and storage of nails, the long-term information obtained and the multiple functions of melatonin, nail melatonin content might complement dim light melatonin onset, which is commonly measured from plasma/saliva samples, paving the way for melatonin research.

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“…L-carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for the subsequent β-oxidation of fatty acids [ 62 ]. Mitochondrial dysfunction is closely associated with aging [ 63 ]. There is an age-related decrease in L-carnitine levels in the brain and plasma of rats, and age-associated mitochondrial decay can be reversed in older rats by feeding them acetylcarnitine [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling of plasma from middle-aged and advanced-age male mice reveals the metabolic abnormalities of carnitine biosynthesis in metallothionein gene knockout mice

Kadota

Yano

Kawakami

et al. 2021

Aging

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Metallothionein (MT) is a family of low molecular weight, cysteine-rich proteins that regulate zinc homeostasis and have potential protective effects against oxidative stress and toxic metals. MT1 and MT2 gene knockout (MTKO) mice show shorter lifespans than wild-type (WT) mice. In this study, we aimed to investigate how MT gene deficiency accelerates aging. We performed comparative metabolomic analyses of plasma between MTKO and WT male mice at middle age (50-week-old) and advanced age (100-week-old) using liquid chromatography with time-of-flight mass spectrometry (LC-TOF-MS). The concentration of N 6, N 6, N 6-trimethyl-L-lysine (TML), which is a metabolic intermediate in carnitine biosynthesis, was consistently higher in the plasma of MTKO mice compared to that of WT mice at middle and advanced age. Quantitative reverse transcription PCR (RT-PCR) analysis revealed remarkably lower mRNA levels of Tmlhe , which encodes TML dioxygenase, in the liver and kidney of male MTKO mice compared to that of WT mice. L-carnitine is essential for β-oxidation of long-chain fatty acids in mitochondria, the activity of which is closely related to aging. Our results suggest that reduced carnitine biosynthesis capacity in MTKO mice compared to WT mice led to metabolic disorders of fatty acids in mitochondria in MTKO mice, which may have caused shortened lifespans.

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Intimate Relations—Mitochondria and Ageing

Cited by 20 publications

References 399 publications

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Nail Melatonin Content: A Suitable Non-Invasive Marker of Melatonin Production

Metabolomic profiling of plasma from middle-aged and advanced-age male mice reveals the metabolic abnormalities of carnitine biosynthesis in metallothionein gene knockout mice

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