The Fading Electricity Theory of Ageing: The missing biophysical principle?

Abstract

Since a few years convincing data are accumulating showing that some of the premises of the master integrative theory of ageing, namely Harman's Reactive Oxygen Species or free radical theory, are less well founded than originally assumed. In addition, none of the about another dozen documented ageing mechanisms seems to hold the final answer as to the ultimate cause and evolutionary significance of ageing. This review raises the question whether, perhaps, something important has been overlooked, namely a biophysical principle, electrical in nature. The first cell on earth started to be alive when its system for generating its own electricity, carried by inorganic ions, became operational. Any cell dies at the very moment that this system irreversibly collapses. In between birth and death, the system is subject to wear and tear because any cell's overall repair system is not 100 percent waterproof; otherwise adaptation would not be an option. The Fading Electricity Theory of Ageing has all necessary properties for acting as a universal major integrative concept. The advent of novel methods will facilitate the study of bioelectrical phenomena with molecular biological methods in combination with optogenetics, thereby offering challenging possibilities for innovative research in evo-gero.

Methods for the discovery of new anti-aging products – targeted approaches

“…Upregulation of chaperones [155] Heat shock response HSP controlled by HSF HSF1-4 in mammals and HSF1 orthologs in Drosophila and Caenorhabditis elegans are required in both DR and IIS pathways as well as in yeast [5] Hypoxia response HIF1 transcription factor Although its mechanism is not exactly understood, increasing active HIF-1 by knocking down of its negative regulator VHL-1 was reported to increases life span [156]; Null mutations in HIF-1 could increase life span [45]; Both HIF-1 over-expression or hif-1 loss of function mutations could extend life span [157] UPR ER Chaperons are controlled by three upstream factors: IRE1, PERK, and ATF-6 causing reduced translation rates; mRNA degradation; transcriptional upregulation of a range of genes including many chaperones; Apoptosis after excessive or prolonged ER stress C. elegans declined the ability to mount a response to ER stress with age and at a similar rate to the loss of activity in the HSR [158] Protein trafficking Reductions in IIS activity Protein degradation UPS Proteins are tagged with chains of ubiquitin and directed to the proteasome for degradation, and autophagy [5] Proteasomal degradation Tissue dependent: worms show a decreased level of UPS-mediated proteolysis, whereas muscle cells remain unaffected in this regard [159] voltage gradient of animal cells is 40 --50 mV, where the membrane inner areas have negative charges [4]. Terminally differentiated cells like those of skeletal muscles as well as stem cells (-90 mV) are usually highly polarized, whereas embryonic and cancer cells are less polarized (between -5 and -30 mV) [34].…”

“…It influences organs that are not mitotically inactive like brain and heart as well as organs with a high cell turnover like blood and epithelial compartment [1][2][3]. The universal dream of humans is to live healthy as long as possible in an enjoyable environment [4]. Mechanisms of aging as well as its impressing and signaling players are partially understood ( Figure 1) and many fundamental questions remain without answers yet.…”

“…In aging research, causes of senescence could be categorized to genetic, biochemical and biophysical aspects in all living animals; thus full understanding of cellular aging requires a holistic point of view [4]. The genetic and epigenetic mechanisms have been criticized in this article, especially those believed to be effective in life span.…”

Biogenêse mitocondrial e exercício físico: hipótese do acoplamento elétrico-transcripcional

“…Outras modifi cações são: aumento na concentração de metabólitos, hipóxia e estresse mecânico 71 . Cogita-se que mudanças na concentração plasmática de Ca 2+ possam afetar as propriedades físicas da cromatina, com possibilidades de facilitação da transcrição, principalmente por expor regiões do DNA a esse processo 72 . Portanto, modifi cações nas propriedades iônicas do tecido muscular podem afetar tanto o DFE como processos relacionados com biossíntese 72 .…”

“…Cogita-se que mudanças na concentração plasmática de Ca 2+ possam afetar as propriedades físicas da cromatina, com possibilidades de facilitação da transcrição, principalmente por expor regiões do DNA a esse processo 72 . Portanto, modifi cações nas propriedades iônicas do tecido muscular podem afetar tanto o DFE como processos relacionados com biossíntese 72 . Essas modifi cações inter-relacionadas podem ser detectadas por sensores, como no caso de proteínas quinases C ("PKC"), calmodulina, AMPK e PPAR-γ ("peroxisome proliferator-activated receptor--gamma"), que desencadeiam cascatas de sinalização intracelular.…”