RE: Hyperfunction Theory of Aging - 2

Pan-mTOR-Hemmung: Letzte Rettung für seneszente Zellen?

Reversal of phenotypes of cellular senescence by pan-mTOR inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789579/

P.S.: Mit der Strategie einer kurzfristigen Verwendung des Pan-mTOR Inhibitors wurden (zumindest im Reagenzglas) keine negativen Auswirkungen auf den Zellzyklus beobachtet:

Zitat

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Importantly, short-term drug exposure had no detrimental effects on cell proliferation control across the life-course of the fibroblasts.

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Alterung ist bekanntlich sowohl eine stochastische als auch eine programmartig ablaufende Angelegenheit.
Doch wie lassen sich diese beiden Aspekte gewichten?

Zitat

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It is generally believed that senescence, which alongside mortality is considered part of the aging process, is a consequence of operation of various adverse forces that are often associated with the effects of the Second Law of Thermodynamics on living things. Senescence, however, is observed only if the effects of these negative events have not been eliminated. When both the cellular- and organismal-level mechanisms are efficient, no effects of damage can be visible, at least in the long run. Effectiveness of these processes depends on external energy supply as well as the existence or availability of an appropriate program (information). Consequently, senescence means accumulation of various types of damage or ballast, both cellular and extracellular.

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One can conclude, therefore, that senescence takes place only if allowed by low effectiveness of life programs of a particular organism. In other words, senescence is a result of allowing for manifestation of unavoidable effects of various adverse Forces.

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we postulate that senescence is driven by stochastic processes only in certain groups of animals represented by insects, roundworms, or mortal forms of immortal species such as medusas. In the case of mammals and birds, quasi-programmable mechanisms of senescence prevail, despite some rare exceptions.

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A limited role of external stochastic factors on human longevity cannot be ruled out, as for example when contact with particular foreign antigens can induce autoimmune aggressive response or as in the case of decay of the teeth system.

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Principles of alternative gerontology
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925816/

Die pharmakologische Altersverzögerung wäre ein riesiger Markt, sobald ein Medikament mit einem risikoarmen Dosierungsschema dafür eine Zulassung erhält.
Logischerweise sind mTOR-Hemmer dafür sehr aussichtsreiche Kandidaten, aber das ist ja alles noch Zukunftsmusik. Oder?

Mausexperimente sind die eine Sache. Wünschenswert wären aber Pharmaunternehmen, die mTOR-Hemmer zur Altersprävention vorantreiben.

Zum Beispiel Unternehmen wie ResTORbio:

Is this the Anti-Aging Pill We've All Been Waiting For?
https://www.technologyreview.com/s/60399...en-waiting-for/

Ist die Lebensverlängerung von Senolyse vornehmlich durch mTOR-Hemmung bedingt?

Anti-aging: senolytics or gerostatics (unconventional view)
https://www.oncotarget.com/article/28049/

Zitat

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Senolytics are basically anti-cancer drugs, repurposed to kill senescent cells selectively. It is even more difficult to selectively kill senescent cells than to kill cancer cells. Based on lessons of cancer therapy, here I suggest how to exploit oncogene-addiction and to combine drugs to achieve selectivity. However, even if selective senolytic combinations will be developed, there is little evidence that a few senescent cells are responsible for organismal aging. I also discuss gerostatics, such as rapamycin and other rapalogs, pan-mTOR inhibitors, dual PI3K/mTOR inhibitors, which inhibit growth- and aging-promoting pathways. Unlike senolytics, gerostatics do not kill cells but slow down cellular geroconversion to senescence. Numerous studies demonstrated that inhibition of the mTOR pathways by any means (genetic, pharmacological and dietary) extends lifespan. Currently, only two studies demonstrated that senolytics (fisetin and a combination Dasatinib plus Quercetin) extend lifespan in mice. These senolytics slightly inhibit the mTOR pathway. Thus, life extension by these senolytics can be explained by their slight rapamycin-like (gerostatic) effects.

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The hyperfunction theory of aging: three common misconceptions
https://www.oncoscience.us/article/545/text/