Mitochondria: Masters of Epigenetics

Tatar, Marc; Sedivy, John M.

doi:10.1016/j.cell.2016.05.021

Cited by 24 publications

(16 citation statements)

References 9 publications

(13 reference statements)

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“…Furthermore, FOXO3a regulated Pink-1 transcription in human cells (42). This adds to the growing evidence that epigenetic factors could well contribute to aging and dementia (69,70).…”

Section: Pink-1 Regulation By Presenilinsmentioning

confidence: 69%

β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog–Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models

Goiran

Duplan

Chami

et al. 2018

Biological Psychiatry

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“…Furthermore, FOXO3a regulated Pink-1 transcription in human cells (42). This adds to the growing evidence that epigenetic factors could well contribute to aging and dementia (69,70).…”

Section: Pink-1 Regulation By Presenilinsmentioning

confidence: 69%

β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog–Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models

Goiran

Duplan

Chami

et al. 2018

Biological Psychiatry

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“…In summary, we showed for the first time that alterations in basal and ATP-linked OCR (but not other specific mitochondrial parameters), in the critical third larval developmental stage, represent a potential predictor of lifespan extension in response to mitochondrial stress, and that these changes most likely precede pro-longevity reprogramming processes ( Figure 4). Although changes in basal and ATP-linked OCR may simply correlate with lifespan extension, due to the observed very strong correlation, it is instead likely that these may promote metabolic, genetic and epigenetic reprogramming later in life [18][19][20], which are, in fact, causally involved in longevity specification. Thus, as opposed to the metabolic inflexibility associated with cellular senescence [21,22] and the detrimental effects observed across species at the cellular and organismal level upon severe mitochondrial dysfunction [23], mild mitochondrial stress leads to less profound alteration of mitochondrial functional parameters.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial bioenergetic changes during development as an indicator of C. elegans health-span

Maglioni

Mello

Schiavi

et al. 2019

Aging

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Mild suppression of mitochondrial activity has beneficial effects across species. The nematode Caenorhabditis elegans is a versatile, genetically tractable model organism widely employed for aging studies, which has led to the identification of many of the known evolutionarily conserved mechanisms regulating lifespan. In C. elegans the pro-longevity effect of reducing mitochondrial function, for example by RNA interference, is only achieved if mitochondrial stress is applied during larval development. Surprisingly, a careful analysis of changes in mitochondrial functions resulting from such treatments during the developmental windows in which prolongevity signals are programmed has never been carried out. Thus, although the powerful C. elegans genetics have led to the identification of different molecular mechanisms causally involved in mitochondrial stress control of longevity, specific functional mitochondrial biomarkers indicative or predictive of lifespan remain to be identified. To fill this gap, we systematically characterized multiple mitochondrial functional parameters at an early developmental stage in animals that are long-lived due to mild knockdown of twelve different mitochondrial proteins and correlated these parameters with animals' lifespan. We found that basal oxygen consumption rate and ATP-linked respiration positively correlate with lifespan extension and propose the testable hypothesis that the Bioenergetic Health Index can be used as a proxy to predict health-span outcomes.

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“…An initial clue that the lifespan extension is indirect came from the observation that activating the UPR mt only extends lifespan if the activation occurs during the larval developmental stages, while lifespan is not extended if UPR mt activation occurs solely in adults . It was subsequently found that during larval stages, UPR mt in neurons triggers a systemic response that induces changes in chromatin in other tissues, and the altered transcriptional changes mediate lifespan extension . Therefore, the UPR mt lifespan extension is not directly associated with the ETC dysfunction (but instead arises from secondary transcriptional changes).…”

Section: Is Increased Mitochondrial Fusion a Proxy For Increased Enermentioning

confidence: 99%

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

Chaudhari

Kipreos

2018

BioEssays

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Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals.

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Mitochondria: Masters of Epigenetics

Cited by 24 publications

References 9 publications

β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog–Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models

β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog–Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models

Mitochondrial bioenergetic changes during development as an indicator of C. elegans health-span

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

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