We had thoughts, at one time, of measuring telomere length in cultured fibroblasts as a index of aging. Why not cultured hair follicles since so many customers report restoration of pigmentation in their hair when consuming BioCu1. Hair follicles are also more mitochondria reliant for their daily activities… unless the aging process is taking its toll. The more we thought about the proper controls, the harder and more expensive things seemed. Perhaps we are over thinking the story.
- Background Cu1 vs Cu2, don’t forget niacin
- Oxidative stress and telomere length
- Exposure to Cu1 and Cu2
- Aging studies: hair follicles in culture
- Follicles from hairs that have turned dark
Background Cu1 vs Cu2, don’t forget niacin
- Ctr1 describes the Ctr1 Cu(I) transport channel. Cu(II) does not get transported until it is reduced to Cu(I). We have always assumed that Cu(I)niacin is more bioavailable than Cu(II) sulfate.
- Copper chaperones deliver Cu in the +1 oxidation state to their target enzymes. This is why we always thought, but never proved, that our copper is better.
- Niacin in the Covid describes how we began to realize that Cu(I) and niacin likely work together.
- Fatty Liver in Cows expands on the interplay between niacin and copper.
Oxidative stress and telomere length
von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002; 27: 339-344 Sci-Hub free paper
Some images were imported of the position of telomeres in a chromosome and examples of telomere shortening with cell divisions. Stem cells, red, keep a fairly constant telomere length. The moment a cell differentiates into a somatic cell (green) with a designated function, telomeres start to shorten. The Hayflick limit (HL) is the number of times a cell may divide before division stops. Crises (blue) may alter gene expression and increase telomere length. PD is the population doubling. (b) The downward green arrows in the von Zglinicki Fig 1 indicates that stress can shorten telomere length more rapidly than normal population doubling. (c) High stress and/or lack of good oxidative defenses, indicated by the width of the blue triangle, can send the telomere length into an almost vertical downward spiral. Good oxidative stress defense can send the telomere length response to
Though this review was published over 20 years ago, it was very insightful and extremely useful for generating hypotheses. The Cu(I) of BioCu1 supplies Cu/Zn superoxide dismutase with a necessary cofactor. Niacin can be a precursor of NADH and NADPH, a cofactor for many anti-oxidant enzymes.
Exposure to Cu1 and Cu2
These are some thoughts on how we might design a cell culture experiment in fibroblasts or maybe even hair follicles in culture. Fibroblasts from individual patients and hair follicles could be studied.
- For starters we will need the culture medium without red dye that is used to indicate pH. We will add the same molar amount of Cu1 used in previous cell culture studies to the culture medium. We will take UV/Vis spectrophotometer scans every one minute for 15 minutes. We will calculate the time window in which we can keep the Cu1 in culture medium on the cells with less than 10% being oxidized to Cu2. (Cupric copper is blue).
- We could add both coppers to cultured follicles and/or fibroblasts for the designated time.
- After the incubation period, the copper containing media could be moved and the copper adhering to the outsides of the cells rinsed away.
- As another control for the Cu1 , we might want to consider the same molar amount of niacin without the copper. As a control for the cupric sulfate we might want to add a non copper sulfate.
- Do we have a way of measuring the copper that was taken up by the cells?
- The next step might be to measure ATP content.
This is already starting to seem like a considerable amount to perform fibroblast or cultured hair follicle experiments. Others are using hair follicles in culture to study telomere aging.
Aging studies: hair follicles in culture
Stone RC, Aviv A, Paus R. Telomere Dynamics and Telomerase in the Biology of Hair Follicles and their Stem Cells as a Model for Aging Research. J Invest Dermatol. 2021 Apr;141(4S):1031-1040. free article
- This review proposed that telomere length dynamics play an important role in the biology of the hair follicle (HF),
- HF are mini organs that show an intriguing aging pattern in humans.
- The pigment producing unit ages quickly but epithelial stem cells (ESC) are more aging resistant. Telomerase deficient mice with short telomeres display an aging phenotype of hair graying and hair loss that is attributed to impaired HF ESC mobilization.
hair follicles are complicated organs
Figure 1 Aging resistance in the cycling human HF. Anti oxidative capacity of the human HF is attributed to ROS scavenging molecules (e.g., catalase, melatonin), oxidative damage response controls (e.g., NRF2), synthesis of neuro hormones influencing mitochondrial function (TRH/TSH), and various DNA repair mechanisms. Similarly, the roles for telomerase and IGF-1 are proposed in the context of TL and TA in the HF. HF, hair follicle; NRF2, nuclear erythroid factor 2- related factor 2; TA, telomerase activity; TL, telomere length;
Reactive oxygen species (ROS) not defined
The lay reader, and even trained biologists, would have to do so much background reading to properly understand what is being said in this review. This review does not discuss the anti-oxidant enzyme Cu/Zn super oxide dismutase simply because no one can think of everything at once.
(a) Young anagen HF with longer telomeres and low TA in the bulge region containing ESC, melanocyte SC and longer telomeres but high TA in the proliferative bulb region containing KC and MCs of the HFPU. (b) In graying hair, bulge melanocyte SCs with short telomeres senesce and limit new HFPU formation, whereas the ROS-sensitive aging HFPU accumulates endogenous and exogenous oxidative damage that shortens telomeres and impairs pigment production; induction of TA might prevent age-associated graying.(c) In cicatricial (scarring) alopecia, critically short telomeres in bulb SCs trigger senescence and apoptosis; with no progenitors and transient-amplifying cells, HF cycling and hair growth are irreversibly halted.
(d) Chemotherapy (e.g., taxanes) damages telomeres and/or low TA HF SCs and also shortens telomeres of the stress-sensitive HFPU. Pretreatment with TA inducers might mitigate chemotherapy-induced HF aging and/or graying and hair loss. (e) Low HF aromatase activity may lower local estrogen and/or progesterone levels; loss of transcriptional stimulation of hTERT production leads to shortened telomeres and premature HF entry into catagen, contributing to AGA. (f) Noxious stimuli shorten hair matrix KC telomeres, limiting cycling of transient-amplifying cells and increasing apoptosis, leading to anagen termination and/or catagen induction and telogen effluvium. AGA, androgenetic alopecia; ESC, epithelial stem cell; HF, hair follicle; HFPU, hair follicle pigmentary unit; KC, keratinocyte; MC, melanocyte; SC, stem cell; TA, telomerase activity; TL, telomere length.
This is all very interesting, but we’ve got to
Follicles from hairs that have turned dark
We have so many anecdotal stories of customers who have had their original hair color return after taking BioCu1. Why not just analyze the follicles from such hairs that have turned dark and compare them with hair follicles from the same customer before BioCu1.