The Problem of Brain Aging, Peter Fedichev

[RapAdmin]

Friends, let me show what is probably the most horrific visuals in the world. While there are questions regarding the origin of the data and the curves, the key takeaway remains consistent across different datasets. It becomes painfully obvious that many traits we associate with intelligence begin to decline long before chronic diseases manifest with age.

This life-long progressive decline is especially pronounced in what’s termed “fluid intelligence.” This refers to our ability to learn new information, adapt to new situations, and solve problems we’ve never faced before.

In contrast, aspects of our “crystallized” intelligence – such as our verbal and arithmetic abilities, which are honed over our lifetime – once mastered early in life, remain largely untouched by age.

Here are my insights from this observation:

Intelligence isn’t linear. If we were to map out these traits, we would identify at least two distinct categories. The first would be linked to crystallized intelligence, encompassing language mastery and numerical skills. The second would align with fluid intelligence, representing what many of us traditionally recognize as intelligence, often measured using tools like the IQ scale or the g-factor.

The dual nature of intelligence suggests that at least in humans the abilities in language and basic arithmetic, compared to the most crucial cognitive functions, are governed by separate systems.

Our abilities to communicate with clarity over elegance, stem from different cognitive functions. As age progresses and we lose neurons, the ability to communicate elegantly persists way longer than the capacity for clear and accurate expression. Be wary of eloquent speakers, for sometimes, eloquence masks a lack of substance.

It’s conceivable that large language models (LLMs) like ChatGPT emulate only one of these systems, most probably the crystallized intelligence. However, fluid intelligence, which I would consider the essence of human intellect, likely functions independently. Supporting this notion, despite their linguistic prowess, the IQ scores of modern LLMs remain surprisingly modest ranging from 83 to 150. Those like me who tried doing their kids homework and some actual work with ChatGPT would not believe 150 though.

This doesn’t mean they lack potential. One of OpenAI’s most innovative strategies has been to train language models through human interaction, allowing the models to learn and evolve. Given that humans possess both crystallized and fluid intelligence, there’s potential for machines to develop in tandem through interactions with us.

What this suggests is that the best is yet to come for these machines. For us, however, the picture is more sobering. As we age, our cognitive profile starts resembling that of an LLM. In a metaphorical sense, the LLM is what remains of our intellect once the ravages of time take their toll.

Carthāgō dēlenda est, Carthage must be destroyed, and so must aging be stopped, boys and girls

As always, if you like what you see here - follow me, hit the like and share - I need your friends. Thank you.

Peter Fedichev,
Source: https://twitter.com/fedichev/status/1694980930501222549?s=20
Peter’s Company is “Gero”, more info: About Gero

Related Reading:

A framework of biomarkers for brain aging: a consensus statement by the Aging Biomarker Consortium

Open Access Paper: framework of biomarkers for brain aging: a consensus statement by the Aging Biomarker Consortium | Life Medicine | Oxford Academic

lnad017.pdf (380.9 KB)

[arugula]

@RapAdmin

the key takeaway remains consistent across different datasets.

I doubt this is true for people in particular professions. I know of people in my department in their 80s who are still publishing original (and valuable) works. They tend to be beanpoles who eat their vegetables, though.

[desertshores]

“In contrast, aspects of our “crystallized” intelligence – such as our verbal and arithmetic abilities, which are honed over our lifetime – once mastered early in life, remain largely untouched by age.”

I don’t necessarily agree with this. I now have to use a calculator for problems I could once do in my head.

I like the chart at the top. I think it is fairly accurate. My perceptual speed, which I define as being able to find things among the clutter, has suffered, and spatial orientation, which I define as something like waking up suddenly and wondering where I am. It takes me longer to orient myself if I leave a building through a different door than when I entered.

[RapAdmin]

What we need is a well-funded clinical trial program (think Impetus Grants or Hevolution Foundation) to create a testing program similar to the “million molecule challenge” for aging, but for brain aging.

And perhaps a phone app for testing fluid intelligence, while tracking supplements and drugs you are taking - so we can gather real world experience faster from all the biohackers and health enthusiasts out there - to see what is working today at mitigating this issue.

I suspect rapamycin helps mitigate these issues Peter cites, but we need data.

Get your Impetus Grant applications in by September 15!

Guide for writing Impetus applications [2023] — Longevity Impetus Grants

Apply — Longevity Impetus Grants

[desertshores]

Personally, I have a stronger inclination towards addressing the markers of brain aging as opposed to those of body aging. After all Stephen Hawking never seemed particularly distressed in his ravaged body.

[RapAdmin]

I agree - and while slowing aging of the brain, and the body, are not mutually exclusive, I also would put a much higher priority on my brain than my body.

I’ve not done a ton of research on the topic - but it seems like there should be an ITP like organization that is focused exclusively on slowing brain aging.

[RapAdmin]

And related to this topic more broadly… this news came out today:

UK Biobank Dementia Risk Score outperforms other widely used scores

Dementia risk study finds 11 key factors behind condition

I had never heard of the “Townsend deprivation index”, so I looked it up… its a measure of poverty.

Townsend deprivation index

Full Paper (open access/download) Here: Development and validation of a dementia risk score in the UK Biobank and Whitehall II cohorts | BMJ Mental Health

[Bettywhitetest]

Inoculation against viral and bacterial infections could be one of the most important aspects to protect against brain aging. I was a bit cavalier about catching colds/flu when working at a college and its contagious students. But catching even a common cold may have a very defined impact on brain health - particularly at middle age. Recent research
The Impact of Routine Vaccinations on Alzheimer’s Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching - IOS Press looks at common vaccines and puts forth even the type of most effective ones - “We also hypothesize that recombinant (when compared with live attenuated) and conjugated (when compared with unconjugated) vaccinations are associated with a greater decrease in AD risk due to the greater protection against infectious disease from Shingrix (compared to Zostavax) and the more robust adaptive immune response induced by conjugatedvaccines.”

I would guess given the pace of new research, an inoculate could be targeted towards brain aging soon. This is a shift from what drug companies have tried spending billions on ineffective prevention or cures.

[Joseph_Lavelle]

I would argue that brain health and body health are the same thing. I am not an expert, but the more I learn about metabolic health, the more I see the impact it has on the brain. Attia was saying “type 3 diabetes” for a long time. And, now I see that Advanced Glycation End-products (which come from metabolic ill health & diet) are believed to damage the brain in addition to the many negative effects on the other parts of the body (eyes, skin, tendons, blood vessels, kidneys, etc.). Of course we should address symptoms with targeted interventions when necessary, but solving root causes provides broad relief (or at least slowing the rate of damage) to brain and body. And just as we need to be physically active to have a “healthy” body, our brain “skills” need to be exercised as well. Conscious brain skills (thinking, remembering, etc.) and unconscious brain skills (coordination, balance, etc.) are subject to the “use it or lose it” rule just like everything else. I just recorded an interview with the author of Physical Intelligence, Dr. Scott Grafton, so I full of brain talk right now.

[John_Hemming]

I agree with that, but also it is interesting how the drop in blood pressure with sleep causes CSF with a high concentration of melatonin to wash the brain cells. Ideally we older people would improve pineal function to do this. However, chugging melatonin to do this via both serum and CSF i think works although i cannot confirm the route, both may work.

[desertshores]

I hope so. I am now “chugging” 100 mg+ per night. As I previously said: I am surprised that it doesn’t cause me any daytime sleepiness.

[John_Hemming]

Sadly i have no measurements on cognitive function. I did think monacolin K caused memory problems so i stopped it and i believe things improved.

There are things i know melatonin does, if you suck it then it reduces gingivitis. I think it also reduces body odour. ( a ros effect)

The general reduction in oxidative stress is good.

[jakexb]

Well this sucks.

I’ve seen this in my parents as they’ve hit the far right section of that chart. They’re not experiencing dementia, but things that require any amount of “figuring out” are just instantly too frustrating now and they become irritated and give up.

[RapAdmin]

Take care of your vision…

More Evidence Linking Impaired Vision and Dementia Risk

and

Diversity in Daily Activities Might Slow Cognitive Decline

[jakexb]

Would be great to see a similar chart following the different types of cognition when treated with PF4 which is, at least by some definition, de-aging brains by decades (in human terms). Probably very difficult to measure different aspects of congnition in mice when they might not even really have all of these types to begin with?

[Bettywhitetest]

Related to the topic, the following showed up in my inbox this morning…

Improving memory with transcranial neuromodulation

[Jonas]

@desertshores

. I am now “chugging” 100 mg+ per night.

How long has you been doing this and what made your decided on the dose? what are the net impact on your sleep and brain health?

[LaraPo]

100 mg of melatonin per night? How many hours do you usually sleep? 3 mg make me very sleepy. I remember reading somewhere (don’t remember where ) that too much of melatonin has the opposite reaction and would contribute to sleepless nights. Do you sleep well?

[desertshores]

Put “melatonin” in the search bar at the top of this thread and read John Hemmings’s comments.

Surprisingly mega-doses of melatonin have not had any effect on my sleep and cause me no daytime sleepiness. Subjectively I have felt zero effects.

I am mainly taking melatonin for its anti-cancer properties, though it has a host of other geroprotective properties. The anti-cancer property is dose-dependent. I am still looking in the literature to find the optimal dose, but the anti-cancer properties seem to start at >20mg/day.

I have been taking a dose up to 20mg nightly since the 1980s.

After reading John Hemming’s posts about taking ~100mg+ nightly, I decided to up my dose.

So far, John Hemming is still ticking and so am I.

I will report if I have any ill effects from taking very high doses.

Among the leading causes of death in the elderly are heart disease, cancer, cerebrovascular diseases, and Alzheimer’s disease.

“It was reported that melatonin may regulate the activation of T/B cells in pinealectomy mice in a dose-dependent manner [40]. Besides, it shows immunomodulation and neuroprotective potential in a pharmacological Alzheimer’s disease mouse model”

“The role of melatonin in cancer treatment and prevention have been widely studied and numerous experimental studies proved the anticancer effect of melatonin against many cancers, including colorectal, breast, gastric, prostate. ovarian, lung, and oral. The anticancer effect of melatonin is mediated by integrated mechanisms, such as apoptosis induction, immune system modulation, targeting cancer altered mechanism, angiogenesis inhibition, and antimetastatic effect.”

A good general purpose about the properties of melatonin:

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

[desertshores]

A few weeks after I started taking rapamycin my sleep greatly improved and I was able to reduce my nightly sleep stack.

Oddly, only because others report otherwise, I have noticed no correlation between melatonin dose and daytime sleepiness. The regimen I am on; diets, rapamycin, supplements, etc. causes me no daytime sleepiness. I did notice that I was no longer sleepy in the afternoons after I started rapamycin.