Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria

Miwa, Soichi; Czapiewski, Rafal; Wan, TF; Bell, Alex; Hill, KN; Zglinicki, Thomas von; Saretzki, Gabriele

doi:10.18632/aging.101089

Cited by 78 publications

(69 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The accumulation of damaged mitochondria in the brain is usually explained as a consequence of the increased ROS production of brain mitochondria during aging [14,47,61,62]. However, the opposite could be also true, that the increase in mtROS is in fact a consequence of the reduced activity of mitochondria.…”

Section: Mitochondrial Ros During Agingmentioning

confidence: 99%

The role of mitochondrial ROS in the aging brain

2017

View full text Add to dashboard Cite

The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging.

show abstract

Section: Mitochondrial Ros During Agingmentioning

confidence: 99%

The role of mitochondrial ROS in the aging brain

2017

View full text Add to dashboard Cite

show abstract

“…Consequently, mTOR signalling and TERT protein could be potential therapeutic targets for neuropathological conditions via improvement of mitochondrial quality and decreased oxidative stress. (194,195) Proteostasis and Protein Seeding Defects in NDD…”

Section: Mitochondrial -Lysosomal Dysfunction In Nddmentioning

confidence: 99%

New Insight in The Molecular Mechanisms of Neurodegenerative Disease

2018

View full text Add to dashboard Cite

B ACKGROUND:Redox and proteotoxic stress contributes to age-dependent accumulation of dysfunctional mitochondria and protein aggregates, and is associated with neurodegeneration. The free radical theory of aging inspired many studies using reactive species scavengers such as alpha-tocopherol, ascorbate and coenzyme-Q to suppress the initiation of oxidative stress. However, clinical trials have had limited success in the treatment of neurodegenerative diseases (NDDs). CONTENT:The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of NDDs. In Alzheimer's disease, the two principal aggregating proteins are β-amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism, corruptive protein templating. The accumulation of redox modified proteins or organelles cannot be reversed by oxidant intercepting antioxidants and must then be removed by alternative mechanisms. Autophagy serves this essential function in removing damaged or dysfunctional proteins and organelles thus preserving neuronal function and survival.SUMMARY: Senescent cells and their senescenceassociated secretory phenotypes (SASPs) may constitute a novel, understudied, and potentially important contributor to neuro-inflammation and subsequent neurodegeneration. Characterization of cellular senescence in the brain could uncover novel therapeutic targets for the prevention and treatment of chronic age-related NDDs. KEYwORDS

show abstract

“…3 The results suggest that upregulation of TERT may be one way to help protect blood vessels in patients with heart disease. 4,5 In contrast, ceramide, a proinflammatory lipid, is required for the often damaging switch from NO to hydrogen peroxide. Gutterman and his colleague, Dr Julie Freed, found that blocking ceramide in blood vessels from patients with heart disease could force them to shift from producing hydrogen peroxide back to NO.…”

mentioning

confidence: 99%

David Gutterman

Jansen¹

2018

Circulation Research

View full text Add to dashboard Cite

Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria

Cited by 78 publications

References 62 publications

The role of mitochondrial ROS in the aging brain

The role of mitochondrial ROS in the aging brain

New Insight in The Molecular Mechanisms of Neurodegenerative Disease

David Gutterman

Contact Info

Product

Resources

About