The Biologic Clock: The Mitochondria?

Harman, Denham

doi:10.1111/j.1532-5415.1972.tb00787.x

Cited by 1,782 publications

(1,053 citation statements)

References 18 publications

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“…Based on findings in the early 1970s that mitochondria can generate reactive species,234 a variant of the free radical theory of ageing, the ‘mitochondrial free radical theory of ageing’ was proposed 235. Consistent with a role of mitochondria as a contributor to age‐related muscle redox changes, reports have shown that isolated213, 236 and intact mitochondria21 in skeletal muscle fibres exhibit an age‐dependent increase in H 2 O 2 generation.…”

Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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“…It is likely that the mechanisms described in these theories may participate to those of aging but none of them can directly explain the causes of aging. Another theory centered on mitochondrial dysfunction was proposed half a century ago (Harman, 1972). This theory is closely linked to the free radical hypothesis of aging but also involves genetic and bioenergetic alterations.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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“…Because the mitochondria are a major source of endogenously generated reactive oxygen species (ROS), it is not surprising that they have been proposed to play a major role in aging [8,9]. The free radical theory of aging predicts that oxidative damage to the mitochondria can lead to an amplifying effect whereby damaged mitochondria release more ROS, further increasing oxidative damage [10]. The accumulation of damaged mitochondria results in a decrease in the capacity to produce ATP.…”

Section: Introductionmentioning

confidence: 99%

Application of capillary isotachophoresis‐based multidimensional separations coupled with electrospray ionization‐tandem mass spectrometry for characterization of mouse brain mitochondrial proteome

et al. 2008

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By employing a capillary ITP (CITP)/CZE-based proteomic technology, a total of 1795 distinct mouse Swiss-Prot protein entries (or 1705 nonredundant proteins) are identified from synaptic mitochondria isolated from mouse brain. The ultrahigh resolving power of CITP/CZE is evidenced by the large number of distinct peptide identifications measured from each CITP fraction together with the low peptide fraction overlapping among identified peptides. The degree of peptide overlapping among CITP fractions is even lower than that achieved using combined CIEF/nano-RP LC separations for the analysis of the same mitochondrial sample. When evaluating the protein sequence coverage by the number of distinct peptides mapping to each mitochondrial protein identification, CITP/CZE similarly achieves superior performance with 1041 proteins (58%) having 3 or more distinct peptides, 233 (13%) having 2 distinct peptides, and 521 (29%) having a single distinct peptide. The reproducibility of protein identifications is found to be around 86% by comparing proteins identified from repeated runs of the same mitochondrial sample. The analysis of the mouse mitochondrial proteome by two CITP/CZE runs results in the detection of 2095 distinct mouse Swiss-Prot protein entries (or 1992 nonredundant proteins), corresponding to 59% coverage of the updated Maestro mitochondrial reference set. The collective analysis from combined CITP/CZE and CIEF-based proteomic studies yields the identification of 2191 distinct mitochondrial protein entries (or 2082 nonredundant proteins), corresponding to 76% coverage of the MitoP2-database reference set.

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The Biologic Clock: The Mitochondria?

Cited by 1,782 publications

References 18 publications

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Mitochondria and aging: A role for the mitochondrial transition pore?

Application of capillary isotachophoresis‐based multidimensional separations coupled with electrospray ionization‐tandem mass spectrometry for characterization of mouse brain mitochondrial proteome

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