People who study NCD (Non Communicable Diseases) and particularly those that focus on the diseases of aging (which I think include many of the NCDs, but not all of them) have a concept of someone having a biological age as well as a chronological age. This guides things like how frail someone is, how well their cognition works, whether they are at the risk of cancer or diabetes or indeed how they look.
Human beings are quite good at judging each other's general health by appearance. That is because the various NCDs tend to correlate with how well the body maintains the skin and when someone is frail it is quite easy to see this by how they move around.
Regular readers of my blog will know that I think this is because the genome stops functioning properly as people get older. In essence cells stop producing the right proteins. I provide full details of this hypothesis on this web page https://citrate.science/2025poster/poster2025.html.
Various approaches have been used to calculate a biological age. Some look at methylation marks on DNA. Others take various biomarkers and try to calculate an age from those. These are always done in years (or months).
However, if the biological age actually primarily depends upon the efficiency of the mitochondria and the membrane potential of mitochondria then perhaps the biological age should reflect that. The membrane potential of mitochondria is measured in millivolts. (normally in the low 100s) Although practically measuring the combination of the membrane potentials of all of the mitochondria in all of the cells is not practical the question is still raised as to whether there is a reason for looking at things this way. I think there is.
What is obviously the case although not necessarily thought about that much is that the average membrane potential of a human egg mitochondria when fertilised is not constant. It is this, however, that drives where development goes both as the egg becomes an embryo and then gets born as a baby. Also when the baby grows up. There is solid scientific research that demonstrates that this starting position is a key foundation as to how good someone's health will be. Also it would sound a bit odd that a baby would be born at a varying biological age.
There are good reasons why it is worth people knowing the state of their mitochondria. There is plenty of evidence that the state of the mitochondria can be improved (and also made worse). Therefore for people who start out with a lower membrane potential it is more important to them to look for interventions that will help prevent cancer or diabetes in later years. In a sense this moves away from the concept of biological age as "age", but more towards it being a health and development status.
At the same time the fact that people start out with different membrane potential averages shows that the links between membrane potential and development are not just linked to an absolute value. The variation in membrane potential links to hormones and the variation in hormones drives development. Hence although for example a lower membrane potential will tend to speed up development such that puberty happens earlier, it probably won't link directly to a multiple of the membrane potential.
People will still want to work out where they are compared to the average and there will be a mechanism to associate an average membrane potential to an age. However, understanding what is happening with the biology is perhaps more useful to people who want to improve their health.
Human beings are quite good at judging each other's general health by appearance. That is because the various NCDs tend to correlate with how well the body maintains the skin and when someone is frail it is quite easy to see this by how they move around.
Regular readers of my blog will know that I think this is because the genome stops functioning properly as people get older. In essence cells stop producing the right proteins. I provide full details of this hypothesis on this web page https://citrate.science/2025poster/poster2025.html.
Various approaches have been used to calculate a biological age. Some look at methylation marks on DNA. Others take various biomarkers and try to calculate an age from those. These are always done in years (or months).
However, if the biological age actually primarily depends upon the efficiency of the mitochondria and the membrane potential of mitochondria then perhaps the biological age should reflect that. The membrane potential of mitochondria is measured in millivolts. (normally in the low 100s) Although practically measuring the combination of the membrane potentials of all of the mitochondria in all of the cells is not practical the question is still raised as to whether there is a reason for looking at things this way. I think there is.
What is obviously the case although not necessarily thought about that much is that the average membrane potential of a human egg mitochondria when fertilised is not constant. It is this, however, that drives where development goes both as the egg becomes an embryo and then gets born as a baby. Also when the baby grows up. There is solid scientific research that demonstrates that this starting position is a key foundation as to how good someone's health will be. Also it would sound a bit odd that a baby would be born at a varying biological age.
There are good reasons why it is worth people knowing the state of their mitochondria. There is plenty of evidence that the state of the mitochondria can be improved (and also made worse). Therefore for people who start out with a lower membrane potential it is more important to them to look for interventions that will help prevent cancer or diabetes in later years. In a sense this moves away from the concept of biological age as "age", but more towards it being a health and development status.
At the same time the fact that people start out with different membrane potential averages shows that the links between membrane potential and development are not just linked to an absolute value. The variation in membrane potential links to hormones and the variation in hormones drives development. Hence although for example a lower membrane potential will tend to speed up development such that puberty happens earlier, it probably won't link directly to a multiple of the membrane potential.
People will still want to work out where they are compared to the average and there will be a mechanism to associate an average membrane potential to an age. However, understanding what is happening with the biology is perhaps more useful to people who want to improve their health.
Comments
https://www.cell.com/cell-reports/pdf/S2211-1247(24)00066-4.pdf
Sustaining a 4mM concentration of the amino acid Proline, over 14 days, caused restoration of mitochondrial function.
ChatGPT tells me that an oral dose of about 26 grams of proline would be sufficient in an average adult Human to achieve the required blood concentration.
Because there is a risk of kidney strain with such large amounts of a singl amino acid, ChatGPT recommended this protocol:
2+ litres of water + electrolytes daily
Arginine or Citrulline: 1–2 grams per day
Vitamin B6: 25–50 mg/day (cofactor for amino acid metabolism)
Zinc: 15–30 mg/day (supports enzyme function)
Glycine: 5–10 grams/day — supports collagen synthesis and detox
Glutamine: 5 grams/day — buffers ammonia and supports gut health
Taurine: 1 gram/day — antioxidant and renal protector
N-Acetylcysteine (NAC): 600–1200 mg/day
Alpha-Lipoic Acid: 300–600 mg/day
CoQ10 (Ubiquinol): 100–200 mg/day
Arginine or Citrulline 1–2 g/day Urea cycle support
All the above for 7 days, then add the Proline.
What do you think?
Based on the findings from the paper, proline supplementation does not trigger NANOG expression directly, but rather mimics or simulates some of its downstream effects.
NONOG triggers transcriptional upregulation of enzymes PYCR1 and PYCR2, but proline supplementation does not. Rather proline supplementation mimics their effect.
NANOG-induced proline biosynthesis leads to AMPK-Parkin-mediated mitophagy, which restores mitochondrial function and reverses cellular aging markers. Proline supplementation removes the need for NANOG activity in activating that pathway.