List of aging-relevant bionumbers/basic units #FirstPrinciples

  • The amount of lysosomal lipofuscin was significantly higher (6-fold) in cell bodies of aged neurons (28
  • Moreover, we observed a drastic reduction in doublecortin expression, a neuronal precursor marker, from 14 to 28 DIV, as described previously
  • John Wentworth and CANanonymity@fightaging also have good lists

I really mitoSENS solves ATP loss with aging due to oxidized redox cell environment.

From 0 tp 40 years old, the plasma redox is roughly -140 mV, then +7 mv/decade rise, until at 70-85 years old, it is -110 mV.
At that high mV current the cell is a continuous oxidative stress state. It is why humans end up dying at 122 years old MLSP.

Lipofuscin granules, which range between 1 and 3 μm in diameter, appear as brownish particles in neuronal cytoplasm and are probably indigestible residues of lysosomes materials

33% of human proteins have four consecutive positive charged amino acids.


for GENERAL bionumbers, see Rob Phillip, Sara Walker, ppl tha Gaurav follow

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The protein concentration in our cells is ~ 200 mg / ml.

bionumbers claims 9%-22% of cellular protein is ribosomal, so multiplying through that would be ~5-10% of energy

That is to say, despite the thousands of noncovalent interactions existing in the structures of folded proteins [27], they are merely 5 to 15 kcal/mol more stable than the unfolded chain [28–30]. For comparison, the dissociation of a single covalent bond requires ~65 to 175 kcal/mol [3]. The low stability of proteins can be explained in two ways. First, even in the lower stability limit (−5 kcal/mol) the folded state is over 99.9% occupied

timescales of motions in proteins

The pK a values of cysteine residues are of critical importance in redox-regulated processes. At physiological pH, the pK a values of protein cysteine thiols vary from 8.2 to 9.9 for solvent-accessible cysteines and therefore have low deprotonation ability [47]. Cysteine thiols within a basic three-dimensional environment (low pK a) are more susceptible to deprotonation and oxidation to sulfenic acid in the presence of ROS

Cytoplasmic and nuclear NAD+/NADH ratios are typically maintained between 60 and 700 in eukaryotes depending on cell type, while the mitochondrial ratio is much lower, around 7–8 (Veech et al., 1972, Williamson et al., 1967, Zhang et al., 2002). Additionally, mitochondria contain a large proportion of cellular NAD+, with estimates ranging from 40%–70% of the total cellular NAD+ pool (Alano et al., 2007, Di Lisa et al., 2001, Tischler et al., 1977).

Due to its low redox potential, guanine is the most vulnerable nucleobase to oxidation. The dominant product of guanine oxidation is 8-hydroydeoxy-guanosine (8-OH-dG) and is, therefore, used as a cellular biomarker of oxidative stress

micronucleus frequency

urinary 1-hydroxypyrene (1-OHP)

Crypts from individuals with POLE L424V showed an average SBS mutation rate of 331 per year (linear mixed-effects model 95% confidence interval (CI) 259–403, P = 10−12) (Fig. 1a,b and Supplementary Note). The POLD1 S478N germline mutations were associated with an SBS rate of 152 per year (linear mixed-effects model 95% CI 128–176*, P* = 10−17), and POLD1 D316N and L474P were associated with an SBS rate of 58 per year (linear mixed-effects model 95% CI 51–65*, P* = 10−22). By comparison, intestinal crypts from healthy individuals acquire 49 SBS per year28 (linear mixed-effects model 95% CI 46–52, P = 10−36). Therefore increased somatic SBS rates are present in all normal intestinal cells of individuals with POLE or POLD1 germline mutations (Fig. 1), although there are differences in mutation rates between POLE (~sevenfold higher than normal individuals) and POLD1 (up to threefold higher) germline mutations, and between different POLD1 mutations

Scientists already knew that occasionally the cell’s protein-building machinery fails to stop where it should. When the machinery doesn’t stop — a phenomenon called readthrough — it creates extended forms of proteins that sometimes function differently than the regular forms.

Cells are highly crowded, with macromolecular concentrations estimated to be between 80 and 400 mg/mL (Cayley et al., 1991; Zimmerman and Trach, 1991). Macromolecular crowding retards diffusion, influences protein volume and association equilibria (Dix and Verkman, 2008; Ellis, 2001; Zhou et al., 2008), including, for example condensate formation in vitro and in vivo (Delarue et al., 2018; Woodruff et al., 2017). These effects are caused by steric exclusion, next to weak chemical interactions (Gnutt and Ebbinghaus, 2016; Rivas and Minton, 2016; Sarkar et al., 2013), and depend on the concentration, size, and shape of the molecules involved and are larger when crowders are smaller sized than the reacting molecule (Marenduzzo et al., 2006; Rivas and Minton, 2016). For example, an increased number of ribosomes slows down diffusion of 20 nm and 40 nm particles, but not average-sized proteins

Charles Brenner, PhD


something like 1 in a million fibroblasts treated w yamanaka factors become iPSCs lots die, others become weird stuff or stay fibroblasts some become tumors & teratomas skilled ppl clone out the iPSCs in vitro in vivo reprogramming is unlikely to be ever tested in ppl

What is the difference between a mitochondria ATP synthase F1 rotor spinning at max efficiency and one that is slowed by high matrix viscosity? The difference is ~40000 rotations per min vs ~8 rpm. At 3 ATP molecules hydrolyzed per rotation, the difference is 120000 or 24 ATPs.

Doris Loh


That is how melatonin can enhance ATP production: by lowering matrix viscosity to elevate not only ATP synthase F1 rotor spin speed, but also expression and activity of complex IV (COX). Want to find out more? Read this groundbreaking paper on melatonin.
Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathologi…

4:21 PM · Apr 2, 2023





Doris Loh

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My latest peer-reviewed paper talked about the importance of lowering viscosity in mitochondria matrix [1]. Why is that important for health?

Lower viscosity can allow the ATPase rotor to spin faster to produce more ATP molecules to support biological functions.

What you may not know is how fast the ATPase F1 rotor actually spins. Most people say the ATP synthase spins at about 9000 rotations per minute, which is about 150 rotations per second. That is super fast, right? Wrong.

According to the results reported in a peer-reviewed study published in 2006 [2] where the authors attached a gold nanobead to track the rotation of the F1 rotor of the ATP synthase in the bacteria Escherichia coli, the F1 rotor can spin at minimum average speed of 380 rotations per SECOND. The results totally shocked the authors who expected a rotation of merely 30 rps.

At maximum, the authors recorded a speed of 671 rps, which means the ATP synthase F1 motor rotates at 40,260 times per minute. Can you imagine what changes in viscosity can do to the speed of rotation in mitochondria ATP synthase?

Variations of up to 5000-fold can be induced by changes in viscous drag, causing the rotor to spin at slower speeds. So at maximum, your mitochondria ATP rotors can be spinning at 40,000 rotations per minute, but at minimum, it could be rolling around at 8 rotations per minute reflecting a 5000-fold reduction [2].

Now do you understand why higher matrix viscosities are associated with all types of illnesses including cancer and neurodegeneration, and why melatonin, being able to reduce viscosity in mitochondrial matrix, can increase ATP production to reverse basically any health challenge imaginable?

If you haven’t read my ground-breaking paper or shared it with your health gurus and/or doctors and healthcare practitioners, perhaps it is time you do so.

Have you had your MEL and AA today?*

  • Disclaimer: These statements have not been evaluated by the Food and Drug Administration. Ascorbic acid, melatonin and any other product mentioned is not intended to diagnose, treat, cure or prevent any disease.


[1] Loh, D.; Reiter, R.J. Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia. Int. J. Mol. Sci. 2023, 24, 5835.

[2] Nakanishi-Matsui, M.; Kashiwagi, S.; Hosokawa, H.; Cipriano, D. J.; Dunn, S. D.; Wada, Y.; Futai, M. Stochastic High-Speed Rotation of Escherichia Coli ATP Synthase F1 Sector: The Epsilon Subunit-Sensitive Rotation. J. Biol. Chem. 2006, 281, 4126–4131.

Proteins account for the majority of biomolecules within a cell. The rate of total protein synthesis has been empirically determined for a number of species (Table 2). Smaller organisms synthesize proteins at higher rates than larger species (Fig. 3A). In mice, protein synthesis takes place at a rate sufficient to replace total body protein mass every ˜5.3 days, while a human requires ˜39.3 days. Of course, renewal rates for individual proteins can vary widely protein-to-protein, ranging from minutes to years (Hetzer 2013).

By current estimates, ~80% of the human genome encodes RNA, while only 2% encodes proteins. Of the whole genome, only a scant 0.4% has been explored by classical, protein-based drug discovery methodologies [Principles for targeting RNA with drug-like small molecules | Nature Reviews Drug Discovery]. The remaining 99.6% of the genome, and in particular the non-coding transcriptome, represents an unexplored universe of novel potential therapeutic targets [Beyond the RNA-dependent function of LncRNA genes] .


For example,
analysis of cells undergoing cellular division in the human
heart revealed that proliferating heart cells can account for
about 14 cells per million in the normal heart, for a total of an
estimated 80,000 cells undergoing cellular division at any given
time. On the other hand, there is an estimated progressive loss
of approximately 7 million heart cells per year. So the normal
process of ongoing regeneration appears sufficient to maintain
normal function. However, while the number of dividing cells
can increase by up to 10-fold in chronic heart disease, this level
of proliferation still seems insufficient to rescue the cardiac
muscle after a heart attack.’