The epigenetic clock theory of aging

My 400th blog post curates a 2018 US/UK paper by two of the coauthors of Using an epigenetic clock to distinguish cellular aging from senescence. The authors reviewed the current state of epigenetic clock research, and proposed a new theory of aging:

“The proposed epigenetic clock theory of ageing views biological ageing as an unintended consequence of both developmental programmes and maintenance programmes, the molecular footprints of which give rise to DNAm [DNA methylation] age estimators.

It is best to interpret epigenetic age estimates as a higher-order property of a large number of CpGs much in the same way that the temperature of a gas is a higher-order property that reflects the average kinetic energy of the underlying molecules. This interpretation does not imply that DNAm age simply measures entropy across the entire genome.

To date, the most effective in vitro intervention against epigenetic ageing is achieved through expression of Yamanaka factors, which convert somatic cells into pluripotent stem cells, thereby completely resetting the epigenetic clock. In vivo, haematopoietic stem cell therapy resets the epigenetic age of blood of the recipient to that of the donor.

Future epidemiological studies should consider other sources of DNA (for example, buccal cells), because more powerful estimates of organismal age can be obtained by evaluating multiple tissues..other types of epigenetic modifications such as adenine methylation or histone modifications may lend themselves for developing epigenetic age estimators.”


I’ve previously curated four other papers which were referenced in this review:


The challenge is: do you want your quality of life to be under or over this curve?

What are you doing to reverse epigenetic processes and realize what you want? Do you have ideas and/or behaviors that interfere with taking constructive actions to change your phenotype?

If you aren’t doing anything, are you honest with yourself about the personal roots of beliefs in fate/feelings of helplessness? Do beliefs in technological or divine interventions provide justifications for inactions?

https://www.nature.com/articles/s41576-018-0004-3 “DNA methylation-based biomarkers and the epigenetic clock theory of ageing” (not freely available)

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The role of DNMT3a in fear memories

This 2018 Chinese rodent study found:

“Elevated Dnmt3a [a DNA methyltransferase] level in the dorsal dentate gyrus (dDG) of hippocampus was associated with the absence of fear renewal in an altered context after extinction training. Overexpression and knockdown of Dnmt3a in the dDG regulated the occurrence of fear renewal in a bi-directional manner.

We found that renewal of remote fear memory can be prevented, and the absence of renewal was concurrent with an elevated Dnmt3a level.

Our results indicate that Dnmt3a in the dDG is a key regulator of fear renewal after extinction, and Dnmt3a may play a critical role in controlling fear memory return and thus has therapeutic values.”


The study was a collection of five experiments investigating causes and effects of biology and behavior. The researchers used different techniques to achieve their goals. I’ve quoted extensively below to show some background and results.

“Alterations in histone acetylation and DNA methylation are involved in the formation and extinction of long-term memory..DNMTs catalyze the cytosine methylation and are required to establish and maintain genomic methylation. Dnmt3a and Dnmt3b are de novo DNA methyltransferases. Dnmt1 is the maintenance DNA methyltransferase.

  1. Dnmt3a expression was elevated in the dDG after extinction training followed by a brief memory retrieval (Rec+Ext), which was associated with the absence of fear renewal when tested in an altered context.
  2. Increasing Dnmt3a expression in the dDG using AAV [recombinant adeno-associated virus] expression led to the prevention of fear renewal following a standard extinction training protocol. 
  3. Knockdown of Dnmt3a in the dDG using CRISPR/Cas9 resulted in fear renewal following Rec+Ext protocol.
  4. Renewal of remote fear memory can be prevented using the Rec+Ext protocol.
  5. The absence of renewal was concurrent with an elevated Dnmt3a level.

Current exposure therapy, although effective in many patients, suffers from the inability to generalize its efficacy over time, or is limited by the potential return of adverse memory in the new/novel contexts. These limitations are caused by the context-dependent nature of extinction which is widely viewed as the biological basis of exposure therapy.

Thus, achieving a context-independent extinction may significantly reduce fear renewal to improve the efficacy of exposure therapy. Our current study suggests that the effectiveness of these approaches, and ultimately the occurrence of fear renewal, is determined by the level of Dnmt3a after extinction training, especially in the dDG.

There are two potential mechanisms underlying extinction, one is erasure or updating of the formed memory, and the other is the formation of a new extinction memory which suppresses or competes with the existing memory in a context-dependent manner. While most studies favor the suppression mechanism in the adult, limited studies do suggest that erasure occurs in the immature animals.

We propose that if Dnmt3a level is elevated with extinction training (such as with Rec+Ext protocol), modification to the existing memory occurs and as a consequence extinction does not act as a separate mechanism or form a new memory; but if Dnmt3a level is unaltered with extinction training, a separate extinction memory is formed which acts to suppress or compete with the existing memory.”


The relevant difference between humans and lab rats is that we can ourselves individually change our responses to experiential causes of ongoing adverse effects. Standard methodologies can only apply external treatments such as exposure therapy and manipulating Dnmt3a levels.

https://www.nature.com/articles/s41598-018-23533-w “Dnmt3a in the dorsal dentate gyrus is a key regulator of fear renewal”

What are the chances?

This 2018 UC Davis anthropology study was on dice changes over two centuries:

“In Roman times, many dice were visibly lopsided..It did not matter what the objects were made of (metal, clay, bone, antler and ivory), or whether they were precisely symmetrical or consistent in size or shape, because, like the weather, rolls were predetermined by gods or other supernatural elements.

Dice, like many material objects, reflect a lot about people’s changing worldviews, Eerkens said. In this case, we believe it follows changing ideas about chance and fate.”


Think of a significant event in your life. Was it brought about by:

  • Fate?
  • Karma, divine intervention?
  • A prayer, belief, placebo-effect process?
  • Randomness?
  • A coin-flip, card-draw, dice-roll decision process?
  • A weighted-probability decision process?
  • Chosen behavior, thoughts, and feelings?
  • Unconscious behavior, thoughts, and feelings?
  • Culturally-guided motivations?
  • Non-arbitrary influences of other parties?

Which one or more of these factors would you now prefer to have been involved?

https://www.ucdavis.edu/news/it-not-how-you-play-game-how-dice-were-made “It’s Not How You Play the Game, but How the Dice Were Made”

Your need to feel important will run your life, and you’ll never feel satisfied

Yesterday’s team meeting at work provided one display after another of a person’s need to feel important. These eye-openers were the reason the scheduled 30-minute meeting lasted 45 minutes.

Although half of the forty or so attendees are under the age of 40, curiously, only two of them spoke during the meeting. I wasn’t among the older people who had something to say.

Not that I wasn’t tempted by the team-building exercise with its Skittles prompts:

  • Red – Tell us something you do well
  • Orange – Tell us something about your childhood
  • Purple – What could you live without?
  • Yellow – What couldn’t you live without?

Participation in the exercise was voluntary. Yes, I drew an orange Skittle.

Everyone knew there wasn’t enough time for each of us to speak and have the exercise become team-building, yet a dozen people piped up. Every one of the self-selected responses could have been prefaced with “I’m important because..”



There are many needs a person develops and tries to satisfy as substitutes for real needs that weren’t fulfilled. In this blog I’ve focused on the need to feel important.

I started with How do we assess “importance” in our lives? An example from scientists’ research choices and highlighted it on my Welcome page:

“Do you agree that an individual’s need to feel important is NOT a basic human need on the same level as nourishment, protection, and socialization? How does this need arise in our lives?”

I supported an explanation of the need to feel important with evidence and arguments on my Scientific evidence page and said:

“If the explanation is true yet someone rejected it, they at least wouldn’t have suffered from exposure to it. They’ll just remain in our world’s default mode of existence:

  1. Unaware of their own unconscious act-outs to feel important;
  2. Unaware of what’s driving such personal behavior; and
  3. Uninformed of other people’s behavioral origins as a consequence of 1 and 2.”

Other examples of substitute needs include:

What do you think? Any arguments for or against interrupting people’s default mode of existence?

The pain societies instill into children

The human subjects of this 2017 Swiss study had previously been intentionally traumatized by Swiss society:

“Swiss former indentured child laborers (Verdingkinder) were removed as children from their families by the authorities due to different reasons (poverty, being born out of wedlock) and were placed to live and work on farms. This was a practice applied until the 1950s and many of the Verdingkinder were subjected to childhood trauma and neglect during the indentured labor.

DNA methylation modifications indicated experiment-wide significant associations with the following complex posttraumatic symptom domains: dissociation, tension reduction behavior and dysfunctional sexual behavior.”


Imagine being taken away from your family during early childhood for no other reason than your parents weren’t married.

Imagine just a few of the painful feelings such a child had to deal with then and ever since:

  • I’m unloved.
  • Alone.
  • No one can help me.

Imagine some of the ways a child had to adapt during their formative years because of this undeserved punishment:

  • How fulfilling it would be to believe that they were loved, even by someone they couldn’t see, touch, or hear.
  • How fulfilling it would be to get attention from someone, anyone.
  • How a child became conditioned to do things by themself without asking for help.

The study described a minute set of measurements of the subjects’ traumatic experiences and their consequential symptoms. The researchers tried to group this tiny sample of the subjects’ symptoms into a new invented category.

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-017-3082-y “A pilot investigation on DNA methylation modifications associated with complex posttraumatic symptoms in elderly traumatized in childhood”


Another example was provided in Is IQ an adequate measure of the quality of a young man’s life?:

“During this time period [between 1955 and 1990], because private adoptions were prohibited by Swedish law, children were taken into institutional care by the municipalities shortly after birth and adopted at a median age of 6 mo, with very few children adopted after 12 mo of age.”

Swedish society deemed local institutional care the initial destination for disenfranchised infants, regardless of whether suitable families were willing and able to adopt the infants. What happened to infants who weren’t adopted by age 1?

Did Swedish society really need any further research to know that an adoptive family’s care would be better for a child than living in an institution?


A third example of the pain instilled into children by societies was related to me last year by two sisters. During the Chinese Cultural Revolution, 1966-1976, among other things, parents were required to be out of their households from dawn to late night, leaving the children to fend for themselves.

One of the daily chores for the sisters at ages 6 and 7, after attending school, was to buy food for dinner and the next day’s breakfast and lunch with ration coupons, and prepare the family’s evening meal. They never met their four grandparents, who had died in ways the sisters either didn’t know or weren’t willing to express to me.

It wasn’t difficult to infer that traumatic childhood events still impacted the women’s lives 50 years later. My empathetic understanding of their histories, though, didn’t improve their current situations.


It’s a challenge for each of us to recognize when our own thoughts, feelings, and behavior provide evidence of childhood pain that’s still with us.

Let’s not develop hopes and beliefs that the societies we live in will resolve these or other adverse effects of childhood trauma its members caused. Other people may guide us, but each of us has to individually get our life back.

Europe, Asia, Africa, Australia, North and South America: every society has its horror stories, and there are people still living who can document last century’s events and circumstances. Have traumatic effects on children from societal policies ceased?

Searching for personal truths – a review of Blade Runner 2049

I saw Blade Runner 2049 yesterday with my 22-year old son. We chose seats with no one in front of us, and got the full impact of sight and sound.

The primary story was one person’s search for his truths: of his origins; of his memories; of his feelings. Who was the infant in the woman’s arms? Are my earliest memories real? Are my feelings true?

The lead character might as well have been lifeless. His activities were dictated by his designated role in society, by what was expected of him. It was no surprise that he preferred ethereal company over people.

He constantly repressed the memories and feelings that were most important to him, that could have given his life meaning. Despite being repressed, his memories and feelings impelled him to discover and confront his truths.

It was a defining moment when his earliest memory was recognized as real:

  • He could feel at last.
  • He could cry at last.
  • He could scream through the cracks in the repression that had produced an unreal, unfeeling existence.

The miracle of life was celebrated, especially at the end. Like the first Blade Runner, society’s members who were deemed unworthy of life were the ones who cherished this fleeting moment most dearly.

See it up close and personal, in a theater with a good screen and sound system.


This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

Review of The Honest Truth About Dishonesty: How We Lie to Everyone–Especially Ourselves

Here’s an Amazon book review I wrote six years ago when I regularly read 2-3 books a week while on the train to and from work. The book served as an example of how behavioral researchers couldn’t reach their stated goals by using standard scientific methods.

Review of The Honest Truth About Dishonesty: How We Lie to Everyone–Especially Ourselves by Dan Ariely

Everybody would benefit from reading this collection of experiments with human behavior.

I think it would be fair to compare the book’s accomplishments with its declared goals. The author stated the book’s primary goal early on when he wrote:

“We need to first figure out what forces really cause people to cheat and then apply this improved understanding to curb dishonesty. That’s exactly what this book is about.

Once we more clearly understand the forces that really drive us, we discover that we are not helpless in the face of our human follies (dishonesty included), that we can restructure our environment, and that by doing so we can achieve better behaviors and outcomes.”

I appreciated the author’s research that described and delineated what his experiments chose to observe. For example, in one series of experiments, people lied in order to get tokens that a few seconds later were exchanged into money. These subjects cheated to an extent that was almost twice the amount of people who lied in order to directly get money.

Another series of experiments showed that when people were tired or stressed, they were more likely to cheat. The amount that mentally exhausted subjects cheated was almost three times the amount of non-stressed subjects.

There was also a series of experiments that tested the “what the hell” effect. The researchers found that the amount of cheating was not linear. A point was frequently reached where the subjects apparently decided to abandon a little bit of cheating, and started to cheat at every opportunity.

The author proposed that a “fake it until you make it” approach doesn’t ultimately lead to honest behavior. He suggested that it would probably start a chain of events that proceeded through the “what the hell” context, where a little bit of cheating became a lot, and ended up with suffering when the truth was eventually revealed.


What these experiments examined wasn’t the origins of dishonest behavior, but rather the middle and ending parts of dishonest behaviors. As such, I didn’t see how the book’s primary goal could be achieved.

Without exploring the precedents to dishonest behavior, we’re also left with a patchwork approach to achieving the secondary goal of changing outcomes by influencing the salient aspects of behavior.

Understanding that I’m not an expert or a researcher, let me offer an approach that could be more conducive to achieving the primary and secondary goals of the book. The necessary but unexplored research area would be along the lines of “What do I feel just before I act dishonestly?”

The subjects’ probable answers to this unasked question would indicate that the person’s unfulfilled needs were in play. These needs are for the most part unconscious, and are the sources of automatic behavior that seeks to fulfill these needs. The outward manifestations of this automatic behavior will lead the subjects to symbolic fulfillment of their old needs.

The subjects in the experiments may not be able to make the connection between their behaviors of say, cheating on a pledge to quit smoking, and their driving forces. This is probably because the subjects weren’t consciously aware of the feelings they had just before they acted.

The researchers may be able to bridge this gap with information obtained from measurements done by fMRIs and other instruments. They can integrate these measurements with the subjects’ reports of their feelings.

To meet the goals of the book, it’s important that the researchers uncover the subjects’ underlying feelings. This is necessary because feelings are usually closer to the causes of a person’s behavior.

The subjects’ behaviors were symptoms of their problems, not the problems themselves. The researchers would be better served to study the entire situation as best they can.


All of us anticipate while we read a book that there will be prescriptions and answers to the circumstances and troubles presented. But because The (Honest) Truth About Dishonesty didn’t identify “what forces really cause people to cheat,” the primary goal, to “clearly understand the forces that really drive us” wasn’t attained.

Realization of the secondary goal is undecided. The author presented several examples of how environments affect people’s dishonesty, such as conflicts of interests. He showed how people’s rationalizations allow them to permit a level of dishonesty that doesn’t harm their ideas about their own morality.

But how can effective and enduring solutions arise “so we can achieve better behaviors and outcomes” when the roots of the behaviors aren’t examined?