We believe what we need to believe

While getting ready for bed tonight, I mused about how my younger brother had such an idealized postmortem view of our father. As he expressed six years ago in an obituary for our high school Literature teacher:

“I’ll remember my favorite teacher and how much he’s meant to my life. My father and Martin Obrentz were the two people who made me care about the things that make me the person I am today.”

Believe what you need to believe, David. But like I said five years ago in Reflections on my four-year anniversary of spine surgery:

“I don’t remember that my three siblings ever received a paddling or belting, although they were spanked. Even before he retired, 17 years before he died, the Miami-Dade County public school system stopped him and the rest of their employees from spanking, whipping, beating, and paddling children.”

It’s extremely important for a child to have a witness to their adverse childhood experiences. Otherwise, it’s crazy-making when these aren’t acknowledged as truths by anyone else. Especially by those who saw but disavow what they saw.

It didn’t really drum into my conscious awareness until tonight that I had such a witness. It wasn’t my mother, of course, since she directed most of my being whipped with a belt, and beaten with a paddle that had holes in it to produce welts. She has denied and deflected my experiences ever since then.

It wasn’t my siblings, regrettably for all of us. It wasn’t our Miami neighbors.

When I was twenty, I ran across a guy 300 miles north in Gainesville, Florida, named David Eisenberg, if I remember correctly. A couple of weeks after we met, he asked if my father was Fred Rice, Dean of Boys, West Miami Junior High School. He said he had been beaten by my father several times.

Those weren’t early childhood memories like mine. Those were experiences of a young man 12-15 years old during grades 7-9 that he remembered more than a decade later.

I was shocked. It came at a time when I wasn’t ready to face facts about my life, though. I needed fantasies, beliefs to smother what I felt.

I don’t expect that the impacts of my childhood experiences will ever go away. After three years of Primal Therapy that ended a decade ago, at least mine don’t completely control my life anymore.

Dr. Arthur Janov put self-narratives of several patients’ experiences into his May 2016 book Beyond Belief which I partially curated in February 2017. It was partial because I couldn’t read much past Frank’s horrendous story in pages 89 – 105, “The Myth of a Happy Childhood.”

Week 4 of Changing an inflammatory phenotype with broccoli sprouts

To follow up Week 3 of Changing an inflammatory phenotype with broccoli sprouts:

1. I started panning 3-day-old broccoli sprouts before microwaving them in 100 ml of water with a 1000 W microwave on full power for 35 seconds. See Week 6 of Changing an inflammatory phenotype with broccoli sprouts for why I stopped panning. This is a typical yield from one tablespoon of broccoli seeds:

Before panning
After panning

If I have fewer broccoli sprouts, I did something to stunt their normal development.

Still not sure that spent broccoli seed coats cause heartburn as mentioned last week. Being locked down for months – or drinking a lot of coffee and tea – may have more to do with it.

2. I continue to see encouraging signs. Made four-to-six-mile-long beach walks Friday, yesterday, and today, and haven’t felt any left-ankle or left-knee inflammation afterwards! Ran a mile yesterday for the first time in a long time, though, and my quads are sore.

3. More often than not, this is my AGE-less dinner (half) then the next day for lunch. I adapted it from pages 198 (Chicken with Lemon-Caper Sauce) and 238 (Homestyle Chicken Soup) of Dr. Vlassara’s AGE-Less Diet: How a Chemical in the Foods We Eat Promotes Disease, Obesity, and Aging and the Steps We Can Take to Stop It.

  • 1 organic lemon
  • 1 organic tomato
  • 2 organic carrots
  • 3 stalks organic celery
  • 4 organic mushrooms
  • 4 cloves organic garlic
  • 6 oz. organic chicken breast fillet
  • 1 cup organic pasta
  • 1 cup frozen organic peas
  • 1 cup sauvignon blanc
  • 32 oz. “unsalted” chicken broth, which still contains 24% of the sodium RDA
  • 2 tablespoons drained capers
  • ground black pepper to taste

Peel the lemon, slice into 1/4″ rounds, de-seed, combine with chicken and wine in a 6-quart Instant Pot.

Add tomato, carrots, celery, mushrooms, garlic, chicken broth. Start a 30-minute Saute.

Take the chicken out at Minute 20, dice it, add back in with the pasta. Add peas at Minute 25. Add capers and pepper five minutes after the Instant Pot turns off.

4. My AGE-less breakfast is 1/2 cup steel-cut oats soaked overnight in 2 cups distilled water. Cook for 18 minutes at 80% power in a 1000W microwave. Eat with a handful of walnuts.

Boring, I know. Waiting for young people to shrug off their behavioral conditioning and lead the way out.

“The angrier you got, the more silly it became. Then you just found yourself in a bigger cage.

We live in a world now of social media where you can say something stupid and get a bunch of attention. But now you’re just imprisoned in some other paradigm.”

Work your voluntary muscles today

This 2020 review by the Aging as a disease research group highlighted their specialty:

“A theory that fits both the aging and the rejuvenation data suggests that aging is caused primarily by the functional (and notably, experimentally reversible) inactivation of resident stem cells, which precipitates deteriorated tissue maintenance and repair and leads to the loss of organ homeostasis.

The damaged and unrepaired tissues suffer changes in their biochemistry, including the molecular crosstalk with resident stem cells, which further inhibits productive, regenerative responses. The inflammatory and fibrotic secretome can then propagate systemically, affecting the entire organism.

Skeletal muscle accounts for almost 40% of the total adult human body mass. This tissue is indispensable for vital functions such as respiration, locomotion, and voluntary movements and is among the most age-sensitive in mammals.

Muscle is capable of active repair in response to daily wear and tear, intense exercises, or injuries. Muscle regeneration relies on the adult muscle stem cells, also called satellite cells.

Rather than a significant decline in the total number with age, most of the data support a dramatic lack of activation of muscle stem cells after injury and a concomitant lack in the formation of progenitors that are needed for repair.

Multiple experimental approaches have been used for tissue rejuvenation and/or systemic rejuvenation; these include ablation of senescent cells and re-calibration of key signaling pathways that are needed for productive stem cell responses. To test the success in experimental rejuvenation, 1-4 approaches are typically applied, and skeletal muscle is well-suited for assaying each one.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007696/ “Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation”

The review had a short section on inflammation details. Not enough, and there’s no tissue repair. Continuing unchecked is a systemic issue that led the reviewers to their paradigm of aging as a disease.

The review concluded with a subject that’s taught in high school, and should be understood at least before college graduation. It’s curious that an item like sample size required emphasis. Maybe research that doesn’t adhere to basics is a current issue?

Week 3 of Changing an inflammatory phenotype with broccoli sprouts

To follow up Week 2 of Changing an inflammatory phenotype with broccoli sprouts:

1. I intend to follow the model clinical trial [1] and pause eating broccoli sprouts after ten weeks. The clinical trial subjects experienced benefits after stopping at Day 70, as measured at Day 90 and Day 160.

Sprouting broccoli seeds takes time and care every day. I may not have that time when everyone gets back to work.

Then again, I live in a state headed by Governor Klan Robes Blackface. Here’s his 1984 Eastern Virginia Medical School yearbook entry, 16 years after Martin Luther King Jr. was assassinated:

He has no empathy for people like the young black man – laid off for four weeks now – who was severely burned as a child, and who was enthusiastically working at Dunkin Donuts. Or the older lady who was trying to get her life back together at Hair Cuttery, still closed.

Who knows when or if people around here will get their jobs back? Politics are a magnet for the worst.

2. I’ve started to see encouraging signs. Over the last few years, I’ve tried to avoid walking long distances where the surface was tilted to my right in order to not overpronate my left foot and aggravate problems mentioned in Week 1.

That was neither an immediate concern during six-mile-long beach walks yesterday and today, nor have I felt any inflammation afterwards!

3. I have Mason jars for sprouting per many YouTube videos, but don’t use them. They’re unsuited for broccoli seeds, which don’t handle extra moisture well.

I’ve had good results with Russian-doll glass bowls. I use a strainer for Round 1, transfer them to a bowl, and wick out extra moisture with a paper towel during Round 2 before putting them back on a pantry shelf. It would be hard to maneuver a paper towel inside a Mason jar.

The bowl at the top left has been replaced by the next size larger than the bowl at the bottom left. Day 3 broccoli sprouts were too crowded to dry in the small bowl.

4. I had heartburn Friday and Saturday after eating 60 grams of 3-day-old broccoli sprouts in 100 ml of water processed with a 1000 W microwave on full power for 35 seconds. Today I removed a thousand spent broccoli seed coats before microwaving, and didn’t have heartburn afterwards. More experiments are required.

[1] 2018 Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects curated in How much sulforaphane is suitable for healthy people?

Aging as an unintended consequence

The coauthors of 2018’s The epigenetic clock theory of aging reviewed progress that’s been made todate in understanding epigenetic clock mechanisms.

1. Proven DNA methylation features of epigenetic clocks:

  1. “Methylation of cytosines is undoubtedly a binary event.
  2. The increase in epigenetic age is contributed by changes of methylation profiles in a very small percent of cells in a population.
  3. The clock ticks extremely fast in early post-natal years and much slower after puberty.
  4. Clock CpGs have specific locations in the genome.
  5. It applies to prenatal biological samples and embryonic stem cells.

While consistency with all the five attributes does not guarantee veracity of a model, inconsistency with any one will signal the unlikely validity of a hypothesis.”

2. Regarding what epigenetic clocks don’t measure:

“The effects of

  • Telomere maintenance,
  • Cellular senescence,
  • DNA damage signaling,
  • Terminal differentiation and
  • Cellular proliferation

have all been tested and found to be unrelated to epigenetic ageing.”

3. Regarding cyclical features:

Both the epigenetic and circadian clocks are present in all cells of the body, but their ticking rates are regulated. Both these clocks lose synchronicity when cells are isolated from tissues and grown in vitro.

These similarities compel one to ponder potential links between them.”

This was among the points that Linear thinking about biological age clocks missed.

4. The reviewers discussed 3 of the 5 treatment elements in Reversal of aging and immunosenescent trends:

“It is not known at this stage whether the rejuvenating effect is mediated through the regeneration of the thymus or a direct effect of the treatment modality on the body. Also, it is not known if the effect is mediated by all three compounds or one or two of them.

What we know at this stage does not allow the formation of general principles regarding the impact of hormones on epigenetic age, but their involvement in development and maintenance of the body argue that they do indeed have a very significant impact on the epigenetic clock.”

Not sure why they omitted 3000 IU vitamin D and 50 mg zinc, especially since:

“It is not known if the effect is mediated by all three [five] compounds or one or two of them.”

5. They touched on the specialty of Aging as a disease researchers with:

“Muscle stem cells isolated from mice were epigenetically much younger independently of the ages of the tissue / animal from which they were derived.

The proliferation and differentiation of muscle stem cells cease upon physical maturation. These activities are initiated in adult muscles only in response to injury.

6. The reviewers agreed with those researchers in the Conclusion:

“Epigenetic ageing begins from very early moments after the embryonic stem cell stage and continues uninterrupted through the entire lifespan. The significance of this is profound as the question of why we age has been attributed to many different things, most commonly to ‘wear-and-tear.’

The ticking of the epigenetic clock from the embryonic state challenges this perspective and supports the notion that ageing is an unintended consequence of processes that are necessary for

  • The development of the organism and
  • Tissue homeostasis thereafter.”

https://journals.sagepub.com/doi/10.1177/1535370220918329 “Current perspectives on the cellular and molecular features of epigenetic ageing” (not freely available)

Linear thinking about biological age clocks

This 2020 review by a Hong Kong company’s researchers compared and contrasted measures of biological age:

“More than a dozen aging clocks use molecular features to predict an organism’s age, each of them utilizing different data types and training procedures. We offer a detailed comparison of existing mouse and human aging clocks, discuss their technological limitations and the underlying machine learning algorithms. We also discuss promising future directions of research.

Biomarkers placed on an intuitive plane of Accuracy vs Utility. Bubble size depends on the number of clocks based on a corresponding aging biomarker.

Currently, DNAm [DNA methylation] is the most accurate and the most frequently used biomarker in biohorology. However, it is harder to apply a DNAm clock compared to clocks based on clinical blood tests. Moreover, DNAm marks often take a long time to emerge in response to aging interventions.

Chromatin structure and telomeres, while intriguing, are too labor intensive and error-prone to be practical.”

https://www.sciencedirect.com/science/article/pii/S1568163719302582 “Biohorology and biomarkers of aging: current state-of-the-art, challenges and opportunities”

We think about chronological age linearly. The reviewers hinted at but didn’t directly assess the extent to which techniques such as linear regression may also influence people to think linearly about biological age.

We experience cyclical changes every day (like sleep), month, season, and longer periods. The reviewers didn’t mention techniques that incorporate our cyclical experiences or assess cyclical biological age.

1. The reviewers pointed out some biological age clock linearity flaws:

“Most aging clocks base their BA [biological age] definitions either on CA [chronological age] or mortality risk. Mortality risk in its turn is derived from demographic tables and can be assumed to be a function of CA in most animals, including human.

Thus, aging clocks are ultimately treating CA as a substitute BA with the caveat that deviations from the actual CA signify better or worse physical fitness when compared to age matched controls. Such a design has several flaws.”

2. They pointed out non-linear characteristics of chromosomal telomere length:

“DNA lesions caused by oxidative stress are repaired less efficiently in telomeric regions, which causes frailty and subsequent telomere shortening. Oxidative stress levels may fluctuate due to habitat, life style, inflammatory diseases – factors that do not necessarily represent replicative clock ticking.

Telomere length typically fluctuates within ±2-4% per month. This led scientists to hypothesize that telomere attrition is an oscillatory process.”

Since cell components show cyclical phases, why wouldn’t cells and each higher living structural level likewise demonstrate cyclical phases? That avenue wasn’t explored.

3. They mentioned the non-linearity of epigenetic clocks:

“If an organism’s DNAm profile is not directly linked to the thermodynamic root of aging [entropy] but instead is a downstream product of competing processes, the applicability of DNAm aging clock methodology is at risk. In this case different aging clocks may not be equally good for different experiment settings.

While genetic, pharmacological and dietary interventions with proven effect on life expectancy change the methylation state of the age-associated CpG sites, they do so in different ways. Caloric restriction is more efficient in preventing methylation loss at hypomethylated sites and methylation gain at hypermethylated sites than rapamycin.

These findings imply that DNAm profiles do not simply gravitate towards the average with age and that there is no single pathway through which all aging processes are imbued into an organism’s epigenetic landscape.”

4. Genetic and epigenetic regulatory pathways were presented with linear thinking:

“Protein structures encapsulating DNA and regulating its accessibility (chromatin and histones) have also been shown to change with age. Moreover, DNAm machinery and histone modifications are interlinked and change throughout aging concordantly.

For example, DNA methyltransferases are attracted by the H3K36me mark. With aging it is less tightly regulated, and thus, more sporadic DNAm occurs, which ultimately translates to epigenetic clock ticking.”

An individual’s capability to regulate their own aging phenotype wasn’t addressed, only externally applied “aging interventions.” Diseases were considered chronological-“age-associated.”

Biological aging was neither viewed as a disease nor as an unintended consequence. If these researchers don’t grasp the foundations of their field of study, why do they work in the biological aging field? It isn’t just math.

It could be that this paper reflected one company’s desire to frame arguments in favor of the company’s offered solution. It could be that spreading the “chronological age is the cause” meme were organizational imperatives for the paper’s sponsors like the Buck Institute for Research on Aging.

Or it may be that the reviewers had other paradigms? What do you think?

Broccoli sprouts oppose effects of advanced glycation end products (AGEs)

This 2020 Australian/UK review subject was AGEs:

“AGEs are formed during cooking and food processing or produced endogenously as a consequence of metabolism. The deleterious effects of AGEs are underpinned by their ability to trigger mechanisms well known to elicit metabolic dysfunction, including the activation of inflammatory pathways, oxidative stress and impaired mitochondrial oxidative metabolism. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes and kidneys.

Reactive carbonyl groups are constantly being produced via normal metabolism and when production overrides detoxification, AGEs accumulate. AGE formation may take several days or weeks to complete in the body.

Factors affecting the AGE content of food depends on the composition of protein, fat, and sugar and the types of processing and cooking methods employed, predominantly on the temperature and duration of preparation. Circulating free-AGEs concentrations [are] a good marker for dietary AGE intake while plasma protein-bound AGEs better represent endogenously produced AGEs.

Receptor for Advanced glycation end products (RAGE) signals via the transcription factor NF-kB increasing gene expression of inflammatory mediators and the production of ROS (reactive oxygen species).”

https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201900934 “The Role of Dietary Advanced Glycation End Products (AGEs) in Metabolic Dysfunction” (not freely available)

Let’s use the Australian 2019 Sulforaphane: Its “Coming of Age” as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease as a reference for how sulforaphane may counter the effects of AGEs:

1. “Activation of inflammatory pathways”

“Antioxidants in general and glutathione in particular can be depleted rapidly under conditions of oxidative stress, and this can signal inflammatory pathways associated with NF-κB. SFN [sulforaphane] has been shown to inhibit NF-κB in endothelial cells.

Two key inflammatory cytokines were measured at four time points in forty healthy overweight people [our model clinical trial, Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects]. The levels of both interleukin-6 (Il-6) and C-reactive protein (CRP) declined over the 70 days during which the sprouts were ingested. These biomarkers were measured again at day 90, wherein it was found that Il-6 continued to decline, whereas CRP climbed again. When the final measurement was taken at day 160, CRP, although climbing, had not returned to its baseline value. Il-6 remained significantly below the baseline level at day 160.”


2. “When production overrides detoxification”

“SFN significantly activates Nrf2 and as such has the potential to modulate the expression of genes associated with redox balance, inflammation, detoxification, and antimicrobial capacity, all key components of the upstream cellular defence processes.

Toxins presented to the Phase 1 enzymes produce intermediate compounds which are sometimes more toxic to cells than the initial toxin. It is therefore important that Phase 2 is sufficiently active that the intermediate products cannot accumulate in the cellular environment.

As a monofunctional inducer, SFN has been described an ideal detoxifier, as its effect on Phase 1 is minimal compared with its significant activity on Phase 2.”

3. “Oxidative stress”

“As a mediator for amplification of the mammalian defence system against various stressors, Nrf2 sits at the interface between our prior understanding of oxidative stress and the endogenous mechanisms cells use to deal with it. Diseases known to be underpinned by oxidative stress are proving to be more responsive to amplification of cellular defences via Nrf2 activation than by administration of direct-acting antioxidant supplements.

SFN, with absolute bioavailability of around 80%, [is] capable of increasing several endogenous antioxidant compounds via the transcription factor, Nrf2.”

4. “Complications of diabetes affecting cardiovascular health, the nervous system, eyes and kidneys”

“Nrf2 is ubiquitously expressed with the highest concentrations (in descending order) in the kidney, muscle, lung, heart, liver, and brain. Nrf2 was shown to prevent endothelial cells from exhibiting a proinflammatory state. Nrf2 is required for protection against glucose-induced oxidative stress and cardiomyopathy in the heart.

Well in excess of 500 genes have been identified as being activated by SFN via the Nrf2/ARE [Antioxidant Response Element] pathway, and it is likely that this underestimates the number as others are being discovered. Of the available SFN clinical trials associated with genes induced via Nrf2 activation, many demonstrate a linear dose-response. More recently, it has become apparent that SFN can behave hormetically with different effects responsive to different doses.

It [sulforaphane] is not only a potent Nrf2 inducer but also highly bioavailable so that modest practical doses can produce significant clinical responses. Other Nrf2 activators [shown in the above image] not only lack potency but also lack the bioavailability to be considered as significant intracellular Nrf2 activators.”

As mentioned in Changing an inflammatory phenotype with broccoli sprouts, per the above bolded part of section 3, I stopped taking N-acetyl-cysteine, the precursor to our endogenous antioxidant glutathione. I stopped taking curcumin last year due to no noticeable effects, probably because of its poor bioavailability. I may soon stop taking more vitamin E than the RDA, and β-carotene.

I changed my diet last summer to reduce AGEs, with mild effects. I expect stronger effects from also daily eating 60 grams of 3-day-old broccoli sprouts that yield 27 mg of sulforaphane after microwaving.

Reanalysis of findings from a senolytics clinical trial

To follow up Preliminary findings from a senolytics clinical trial:

“The central hypothesis tested in our article is that a brief course of the senolytic drug combination, Dasatinib plus Quercetin (D+Q), can reduce senescent cell abundance in humans, specifically focusing on targeting adipose tissue in subjects with diabetes and kidney dysfunction, a condition in which adipose tissue senescent cell burden is known to be increased.

Although we reported a statistically significant decrease in skin senescent cells in the 9 subjects whose skin data were reported in the original article, that conclusion did not hold up upon reanalysis.

The overall conclusion of our article that D+Q can target senescent cells in humans holds upon reanalysis of the data, at least in adipose tissue and as reflected by a composite of blood SASP [senescence-associated secretory phenotype] factors, but we have not shown this in skin here.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994619/ “Corrigendum to ‘Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease’”