Paradoxes of Aging

Blagosklonny, Mikhail V.

doi:10.4161/cc.6.24.5124

Cited by 80 publications

(96 citation statements)

References 68 publications

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“…2A). As Blagosklonny points out, this is paradoxical (6). Why, under conditions of unrestricted food, should organisms limit investment of resources into somatic maintenance?…”

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 98%

“…Critically, it provides a template for integrated evolutionary mechanistic theories of aging. However, according to the hyperfunction model, aging is not driven by molecular damage, nor do somatic maintenance processes protect against aging (except in the sense that they are needed acutely to keep an organism alive) (6). In this case, the disposable soma theory cannot be true (6,7).…”

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 99%

“…In broad terms, what Blagosklonny has done is to remove certain elements from the existing conceptual framework of biogerontology, add some new ideas, and rearrange the rest. The result is a radically new, coherent integrated theory that presents a very different big picture of aging (4)(5)(6).…”

Section: Aging As Quasi-programmed Hyperfunctionmentioning

confidence: 99%

“…According to the hyperfunction theory, insofar as aging rate can be altered by growth control pathways, it is quasi-programmed. Here, quasiprogram means an unintended continuation of the developmental program (4,6). The importance of the prefix quasi-is that the evolved function of the program is not to cause aging.…”

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 99%

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Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

Gems

Guardia

2013

Antioxidants & Redox Signaling

157

122

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Significance: The biological mechanisms at the heart of the aging process are a long-standing mystery. An influential theory has it that aging is the result of an accumulation of molecular damage, caused in particular by reactive oxygen species produced by mitochondria. This theory also predicts that processes that protect against oxidative damage (involving detoxification, repair, and turnover) protect against aging and increase lifespan. Recent Advances: However, recent tests of the oxidative damage theory, many using the short-lived nematode worm Caenorhabditis elegans, have often failed to support the theory. This motivates consideration of alternative models. One new theory, conceived by M.V. Blagosklonny, proposes that aging is caused by hyperfunction, that is, overactivity during adulthood of processes (particularly biosynthetic) that contribute to development and reproduction. Such hyperfunction can lead to hypertrophy-associated pathologies, which cause the age increase in death. Critical Issues: Here we assess whether the hyperfunction theory is at all consistent with what is known about C. elegans aging, and conclude that it is. In particular, during adulthood, C. elegans shows a number of changes that may reflect pathology and/or hyperfunction. Such changes seem to contribute to death, at least in some cases (e.g., yolk accumulation). Future Directions: Our assessment suggests that the hyperfunction theory is a plausible alternative to the molecular damage theory to explain aging in C. elegans. Antioxid. Redox Signal. 19, 321-329.

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“…2A). As Blagosklonny points out, this is paradoxical (6). Why, under conditions of unrestricted food, should organisms limit investment of resources into somatic maintenance?…”

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 98%

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 99%

Section: Aging As Quasi-programmed Hyperfunctionmentioning

confidence: 99%

Section: Hyperfunction and The Evolution Of Agingmentioning

confidence: 99%

See 2 more Smart Citations

Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

Gems

Guardia

2013

Antioxidants & Redox Signaling

157

122

View full text Add to dashboard Cite

show abstract

“…145 We already discussed that the same lowinsulin action can be either life-shortening or life-extending, depending on whether it is due to mTOR over-activation or results in mTOR deactivation, respectively. 149 Similarly, diabetes type II due to overactivated mTOR leads to complications, increased morbidity and mortality, but if the diabetic-like condition is due to deactivation of mTOR (by starvation or rapamycin), then it might be beneficial.…”

Section: Summary and Further Perspectivementioning

confidence: 99%

Rapamycin-induced glucose intolerance: Hunger or starvation diabetes

Blagosklonny

2011

Cell Cycle

Self Cite

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Induction of DNA damage signaling by oxidative stress in relation to DNA replication as detected using “click chemistry”

Zhao¹,

Dobrucki²,

Rybak³

et al. 2011

Cytometry Pt A

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Induction of DNA damage by oxidants such as H2O2 activates the complex network of DNA damage response (DDR) pathways present in cells to initiate DNA repair, halt cell cycle progression, and prepare an apoptotic reaction. We have previously reported that activation of Ataxia Telangiectasia Mutated protein kinase (ATM) and induction of γH2AX are among the early events of the DDR induced by exposure of cells to H2O2, and in human pulmonary carcinoma A549 cells, both events were expressed predominantly during S-phase. This study was designed to further explore a correlation between these events and DNA replication. Toward this end, we utilized 5-ethynyl-2′deoxyuridine (EdU) and the “click chemistry” approach to label DNA during replication, followed by exposure of A549 cells to H2O2. Multiparameter laser scanning cytometric analysis of these cells made it possible to identify DNA replicating cells and directly correlate H2O2-induced ATM activation and induction of γH2AX with DNA replication on a cell by cell basis. After pulse-labeling with EdU and exposure to H2O2, confocal microscopy was also used to examine the localization of DNA replication sites (“replication factories”) versus the H2AX phosphorylation sites (γH2AX foci) in nuclear chromatin in an attempt to observe the absence or presence of colocalization. The data indicate a close association between DNA replication and H2AX phosphorylation in A549 cells, suggesting that these DNA damage response events may be triggered by stalled replication forks and perhaps also by induction of DNA double-strand breaks at the primary DNA lesions induced by H2O2

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Paradoxes of Aging

Cited by 80 publications

References 68 publications

Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

Rapamycin-induced glucose intolerance: Hunger or starvation diabetes

Induction of DNA damage signaling by oxidative stress in relation to DNA replication as detected using “click chemistry”

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