Protein Synthesis and Aging: eIF4E and the Soma vs. Germline Distinction

Tavernarakis, Nektarios

doi:10.4161/cc.6.10.4230

Cited by 28 publications

(22 citation statements)

References 54 publications

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“…However, replicative age did not affect the mRNA levels of p400-TIP60 complex subunits (TRRAP, p400, TIP60, GAS41). These results indicate that decreased protein levels of the p400-TIP60 complex are mediated by a transcription-independent mechanism in senescent IMR-90 cells, probably through decreased protein synthesis (Tavernarakis, 2007). Our result is consistent with previous studies of human renal epithelial cells showing that p400 expression is decreased during cellular senescence which is caused by transcriptional or post-transcriptional downregulation of p400 (Young et al, 2008).…”

Section: Upregulation Of P21 Gene Occurs Without Sustained P53 Activasupporting

confidence: 95%

“…Since our analysis was based on observations from a large pool of heterogeneous cell populations in terms of PDL that might undergo different senescence pathways, we cannot exclude the possibility that normal p53 activation occurs in a small subset of cells (Herbig et al, 2004). Nonetheless, the protein synthesis and signal transduction pathways seem to generally diminish with aging (Tavernarakis, 2007), potentially explaining the general decrease in protein levels in our studies.…”

Section: Discussionmentioning

confidence: 94%

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Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur in senescent IMR-90 human fibroblasts

Lee¹,

Lau²,

Meredith³

et al. 2012

Mechanisms of Ageing and Development

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Section: Upregulation Of P21 Gene Occurs Without Sustained P53 Activasupporting

confidence: 95%

Section: Discussionmentioning

confidence: 94%

Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur in senescent IMR-90 human fibroblasts

Lee¹,

Lau²,

Meredith³

et al. 2012

Mechanisms of Ageing and Development

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“…99 Fourth, inhibition of translation extends lifespan. 70,71,100,101 In some studies it was even concluded that autophagy is not sufficient for lifespan extension. 102 Finally, the role of autophagy (as well as other functions downstream of TOR) in longevity could vary in different species from yeast to mammals.…”

Section: Autophagy: Ros or Tormentioning

confidence: 99%

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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“…3 One would expect that further inhibition of protein synthesis would decrease life span. Paradoxically, inhibition of mRNA translation and of protein synthesis extends lifespan in the worm C. elegans.…”

Section: Paradox 3: the Protein Synthesis Paradoxmentioning

confidence: 99%

Paradoxes of Aging

Blagosklonny¹

2007

Cell Cycle

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Protein Synthesis and Aging: eIF4E and the Soma vs. Germline Distinction

Cited by 28 publications

References 54 publications

Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur in senescent IMR-90 human fibroblasts

Decrease of p400 ATPase complex and loss of H2A.Z within the p21 promoter occur in senescent IMR-90 human fibroblasts

Aging: ROS or TOR

Paradoxes of Aging

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