Program‐like aging and mitochondria: Instead of random damage by free radicals

Blagosklonny, Mikhail V.

doi:10.1002/jcb.21602

Cited by 40 publications

(32 citation statements)

References 118 publications

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“…Such accumulation of defective or 'malignant' mitochondria may occur with age due to inhibited autophagy (degradation in lysosomes) of mitochondria (reviewed in ref. 30). Accumulation of defective mitochondria probably plays a role in some diseases of aging such as hearing loss.…”

Section: Theoretical Problems Of the Ros Modelmentioning

confidence: 99%

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Aging: ROS or TOR

2008

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It is widely believed that aging is caused by the accumulation of random molecular damage due to reactive oxygen species (ROS). Here I discuss evidence for and against the ROS theory. Remarkably, even supporting evidence has an alternative explanation, consistent with the model that aging is driven by the TOR (target of rapamycin) signaling pathway. PrologueThis article may seem provocative because it presents a novel point of view on aging. It discusses that aging is not the life-long accumulation of molecular damage, is not decline and is not caused by reactive oxygen species (ROS). And data that support the ROS theory have an alternative explanation. The article suggests that aging is a consequence of over-activation of growth-promoting signaling pathways such as the TOR (target of rapamycin; also known in mammals as mTOR) pathway. Of course, ROS induce molecular damage. However, ROS-induced molecular damage is not lifelimiting, simply because the TOR-driven aging terminates life first. Therefore, TOR (mTOR) cannot be incorporated into the ROS theory. But ROS, which play a signaling role in the TOR pathway, can be incorporated into the TOR model. Some opponents have called this point of view extreme, one-sided and unbalanced. But a model is either correct or incorrect. If the article were "less extreme", thus allowing TOR to be incorporated into the ROS model, then it would be plainly wrong. It would be a completely different model, with aging seen as decline, not as hyperfunction.The TOR-centric model resolves paradoxes of aging. 1 It is believed that aging is extremely multifactorial and complex and that all contradictions just illuminate its complexity. From the TOR perspective, the complexity is turning out to be simplicity. 1 But this article is not about a new theory of aging. A general outline of the theory was published in 2006. 2 This article has a special focus: TOR or ROS. In particular, it discusses how the same data that support the ROS model can be explained by the TOR model. Most importantly, this may have tremendous clinical applications to prevent age-related blindness and memory loss, cancer and stroke, for instance, given the existence of prescription drugs that inhibit TOR. 3,4

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Section: Theoretical Problems Of the Ros Modelmentioning

confidence: 99%

“…31,32 If so, defective ("malignant") mitochondria are a pro-apoptotic effector of the TOR pathway. 30 …”

Section: Theoretical Problems Of the Ros Modelmentioning

confidence: 99%

Aging: ROS or TOR

2008

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“…[1][2][3][4][5][6][7][8][9][10] As a consequence, dramatic reductions in oxygen consumption occur, shifting the entire body toward glycolytic metabolism or aerobic glycolysis [11][12][13] (Fig. 1).…”

Section: Aging Metabolic Decline and Cancermentioning

confidence: 99%

Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism

et al. 2012

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“…[7][8][9][10][11][12] Recently these pathways have been shown to play critical roles in the preventing aging and senescence. [12][13][14][15][16] Thus these pathways have been targeted to promote longevity by altering the aging process which might be enhanced when these pathways are hyperactivated. these pathways is mediated by a series of kinases, phosphatases and various exchange proteins.…”

Section: Introductionmentioning

confidence: 99%