When things become free

From Kevin Kelly:

A universal law of economics says the moment something becomes free and ubiquitous, its position in the economic equation suddenly inverts. When nighttime electrical lighting was new and scarce, it was the poor who burned common candles. Later, when electricity became easily accessible and practically free, our preference flipped and candles at dinner became a sign of luxury.

🤔

I started thinking about what might happen to important areas of our lives if suddenly the currently “luxurious” thing were to become ubiquitous and free:

What if smartphones were free and everyone had one? Luxury would the person who didn’t need a phone, perhaps because they have assistants, or perhaps they have a job that doesn’t require smartphone access.

What if calories were free? Then eating less – or not eating at all – would become the new luxury. Fasting. Caloric restriction.

What if computers were free? Similar to smartphones above, perhaps luxury then is not needing a computer at all. Or having an army of assistants (AI or human) that use computers for you. Or living off the grid.

What if car travel were free? Imagine an era of free energy + self driving cars. Imagine summoning a private car to drive you anywhere you want, within a reasonable distance, and all for the cost of a bus fare or less. Then luxury might look like someone who doesn’t travel at all – who has built himself an all-inclusive resort with every comfort they could need: a home gym, a home garden, a home theater, and so on. Sorta like what the elites did during covid lockdowns.

What if quality healthcare were free? Imagine a machine or system that could examine, diagnose, and cure you of 98% of common ailments, all for a very low fee or completely subsidized by the government. What would an inversion look like? Would people purposefully get sick so they’d better appreciate health? Or would they invest so much in preventive healthcare and personal fitness in order to eliminate the need for common medical treatment?

What if high quality university education were free and universally accessible? Perhaps luxury would be those who skipped university entirely (not unlike today’s fetish around college-dropout-billionaires), either to pursue a career early, or to follow their hobbies and passions (like art or music). Or luxury could be homeschooling, people who opt-out of the institutional education system.

What if life extension were free? What if you could add as many years to your life as you wanted? Then perhaps luxury would be choosing to die.

And this is what “free university education for everyone” looks like to Stable Diffusion:

Podcast notes – David Sinclair and Matthew La Plante on brain health and brain aging

Hosts: David Sinclair and Matthew LaPlante

6.2M Americans over 65 living with dementia
This number will continue to grow

If you reverse aging, Alzheimers and dementia can go away, you can recover memories

Epi-genome – computer that reads the genome (genetic) software
Ex differentiation – when a cell begins to malfunction, forgets its proper role

Horvath clock – your biological (aging) clock
Measures DNA methylation
Can measure this for a dollar
Measured 112 yo woman, and brain organs were much younger than all others

Brain ages slower than rest of body
Partially due to protective barrier (skulls)
Brain cellular turnover is low
Volume of brain after 40 reduces 5% per decade

For most of history, we only really needed brain until 40s / 50s – but now we live until 70s / 80s
Our fast changing world – need to constantly learn and adapt, need more brain plasticity

3 longevity pathways that respond to adversity
1. M-tor
2. AMPK – low glucose
3. Sirtuins
They all work together, protect body
Proper lifestyle changes generally benefit all three

M-tor role in autophagy – recycling and garbage collection

Sirtuins – 7 genes in body
Sirt1 (sp?) seems most important for brain aging
Need to up-regulate sirtuins, can do it with NAD boosters, resveratrol

Diet and exercise
Mediterranean diet – very clear benefits to brain aging, proven to reverse mild cognitive impairments, in fact its a spectrum the more Mediterranean your diet the better the outcomes
Olive oils (oleic acid, also in avocados), red wine (polyphenols, resveratrol), less red meat
Standard Western diet has much more fat and red meat

B-vitamins are important – especially vegetarians can be deficient
Aging is accelerated when lacking B-vitamins

Alcohol, smoking, also harmful – related to homo-cysteine

Doctors can see blood vessel lining in back of retina – if they see a lot of plaque, high chance of imminent heart attack / death

“Your eyes are your brain” – when you look at someone’s eyes, you’re looking at their brain

Fatty acids
Normal diets often lack omega3 fatty acids (like in fish) – help with wound healing, depression
Eat salmon, mackerel, sardines
If plant based, find ALA high foods – flax seeds, walnuts, linseed
Oleic acid in olive oil and avocados is important too
Seaweed

Why omega 3s?
Important fat compound in brain, insulating material for brain, protects against inflammation

Exercise
Even walking can > better memory and cognition
Activate sirtuins pathways
Relates to executive function
Study: 6 months of cardio exercise for 55+ showed dramatic improvement in aging indicators
Study: 10 weeks of strength exercise increased BDNF, marker of new nerve cells, brain re-growth
“Get moving before it’s too late”

Supplements
Metformin – AMPK activator (which also affects sirtuin pathway)
Fish study: metformin in their food > better performance on memory tests
Cells make more mitochondria, lower blood sugar in bloodstream
High blood sugar is bad for all tissues, especially cardiovascular system
2019 study: Metformin > 55% prevention in diabetes incidence
Metformin might directly impact NAD too
NAD levels go down over time, increasing degradation as we age
NAD boosters to help cognitive functioning, brain repair
2004 study: NAD-H treatment slowed Alzheimers

Sleep
Hypothalamus controls your daily rhythms
Sirt1 and NAD important role in your wake / sleep cycle
If you lose Sirt1 / NAD functioning, you won’t sleep well, age prematurely
As you get older, you lose ability to sleep
Intervene with diet, exercise, supplements
How to sleep well?
Supplements: MNN (sp?), magnesium, l-theanine
Get light right when you wake up
Can supplement with blue light machines
One night of sleep deprivation increases amyloid beta production by 5% (bad)
If you deprive rats of sleep, get diabetes in 2 weeks

Podcast notes – The Economist overview of longevity and anti-aging research (Babbage)

Podcast: The Economist (Babbage)

Rich world life expectancy is 70+, increasing by average of 5 hours per day

Victorian times – terrible doctors, but great engineers – clean water, better nutrition – lifespan really improved

20th c – defeated many infectious diseases, antibiotics after WW2, another step change

Countries with highest lifespan – Southern Italy, Japan
“can get to 85 just by living like the Japanese”

Why do we age?
Genetic material gets damaged
Machinery of gene expression
Major cellular molecules – protein synthesis, mitochondria go wrong, proliferation of senescent cells

Aging is root cause of many diseases – cancer, cardiovascular, neuro degenerative
If we can combat these fundamental aging pathways, we can fight a lot of these diseases

Most promising is altering blood plasma
Parabiosis – mice blood systems being shared, old mice improves from sharing with young mice
(Gavin Belson from the show Silicon Valley)

Cellular rejuvenation – transcription factors (Yamanaka factors)
If you apply them to body cells, they will “take them back to factory settings”
Yamanaka – Japanese biologist, won Nobel Prize – creating pluripotent stem cells
Can create cells identical to your body’s cells for experimentation and treatment
Risk of uncontrolled proliferation (cancerous cells) if mis-used

New research shows you can reverse (some) epigenetic marks of aging
Treatment on old mice becoming metabolically younger, can repair skin wounds better, seem to be healthier, expect to live longer
Proof of concept stage

Silicon Valley
Altos Labs – $3B in funding, “world’s best financed startup company” – led by prominent researchers
Focus on Yamanaka factors and “integrated stress response”, cells that have gone AWOL – metabolic problems, diabetes, Parkinson’s
Trying to develop novel approach to diseases caused by cellular malfunction – indirectly improving aging
“Natural selection cares less and less about multi cellular organisms as they get older”

Heart attack – lost tissue isn’t replaced, a scar forms, causing loss of function, so the heart remodels, get larger, walls get thinner, can lead to heart failure
Today transplantation is only cure, life expectancy afterwards is only 10 years
Identify cell types in heart that can be stimulated to create more healthy tissue
Trying to restore embryonic cell development in adult hearts (eg, like epicardial cells)
“regrowing parts of the heart”
Identify high risk patients, give them pre-treatment (like a pill), to prime cells to heal / repair when heart attacks happen
Organoids – small organs in dish – multiple cell types – eventually “derive heart in a dish”

Unity Biotechnology
Senescent cells – “cells in your body that have turned against you”
Senescent cells cause damage to neighboring cells
It’s a slow insidious assault inside your body
Vision is take a pill, get rid of your body’s senescent cells
In mice, experiments to tag these cells and remove them – cognition better, improve health
Now research focus is on the eye – to improve vision, suffering macular degeneration / color loss

Much of this research may not extend lifespan but can extend healthspan – number of healthy quality years
Lot of these treatments work for everything except for your brain – more complex and unpredictable
“What do you do about the brain?”

Podcast notes: David Sinclair’s Lifespan podcast on longevity benefits of exercise, heat, and cold

David Sinclair (DS)
Lifespan podcast

Notes from last episode:
-Too much iron can accelerate aging
-Typically long lived have low iron levels
-So limit meat intake – red meat high in iron
-Also multivitamins w/ iron

Recs from last episode:
-Plant-based diet
-Low iron levels
-Eat less often
-DS eats one meal / day

Found mutant worm living 2x longer – single gene mutation – was insulin receptor gene
Start of revolution in manipulating genes for health and longevity
It’s related to stress resistance

Modern society is too comfortable
Need to find more of the right stressors
Examples: fasting / IF, exercise
Sitting down is bad for you – muscles atrophy, testosterone decreases

Get moving!
Exercise can slow down and even prevent cancer
Reduces all cause mortality
Walking after meal controls glucose
Both low and high intensity exercise

High intensity = hypoxia = panting and can’t carry on a chat
Turns on helpful genes
Generates free radicals
Mitochondrial hormesis

Aging reduces glucose sensitivity – and exercise increases it

Can measure biological age now (Horvath Clock) – exercise slows down this clock
Insight Tracker blood test to do this test

Standard sex isn’t aerobic / intense enough, and only lasts on average 5 minutes

Recommends 75 minutes of vigorous exercise a week = ~10 minutes / day

Less than 50 resting heart rate is good target

Benefits of weight training
-DS does it every other day or more
-Maintains hormones (eg, testosterone), posture, aesthetic
-Lose muscle mass as you get older – breaking hip is major risk to mortality
-Thighs, butt, back muscles – large muscle groups – most impact on testosterone

Senescent cells – zombie cells, can secrete damaging chemicals and don’t have any benefits
Exercise kills senescent cells

Overall takeaways
1. Low intensity exercise – “get off your butt” – 4K steps / day
2. High intensity exercise – 10 mins / day, lose your breath
3. Muscle building – weights, pushups + situps

Hyperbaric chambers = low oxygen environments, mimicking hypoxia
Study of daily sessions ~90 minutes
Showing cognitive improvements
Improve dementia / Parkinson’s
Seems to work similar to exercise
Impact on telomere length (anti-aging)

Benefits of COLD exposure
Production of brown fat (beige fat) – found in babies, helps them stay warm
Adults have brown fat, mostly on back
When cold, this revs up metabolism, burns white fat, and improves overall health
Reduces free radical load

Dwarf mice living 3x longer than normal mice
They were shivering (didn’t have companion)
With buddy, the life extension went away (!) – because they weren’t shivering (no longer cold)
Old mice don’t make brown fat as well as young mice – why you shouldn’t wait to do it

Ways to get cold therapy
-Cold showers
-Sleep with little or no clothes / covers
-Ice baths

Benefits of HEAT exposure
One of most ancient therapies
Now in Finland, Scandinavia

Men who sauna bathe a few times a week have dramatic reduction in heart attacks and cardio disease
Activates heat shock proteins
Not sure what dosing is right – but no evidence so far you can over do it

DS used to do heat sauna + ice bath cycles multiple times (reader beware)

Some evidence that infrared sauna can have additional benefits (over dry sauna)