Tag: anti aging

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 on the science of looking younger (Longevity Podcast)

David Sinclair – Science of looking younger
Co-host Matthew LaPlante

We’ve evolved to have children up to ~30yo – after that risks increase
Infertile ~40yo – menopause – lots of physical changes
Estrogen + progesterone / HRT treatment can be beneficial
Most women don’t know their baseline levels especially during menstrual cycles

Truth to “you’re as old as you look” – subjective physical appearance is correlated with longevity

Importance of skin health
Skin is body’s largest organ
Simple skin test – palm on table, pinch back of hand, skin should return to place in <2 seconds when young – by 40s to 50s it’s <10 seconds
Problem of epidermal thinning – menopausal women, older men
Bruising, ripping, tearing – becomes life or death especially when older
Health of skin cells is very correlated with measured biological age

Skin is full of dying cells (senescent cells)
The dying cells secrete bad chemicals, and if you kill these cells it can improve health

Prevention –
Avoid UV light
Wear sunscreen – 10-20 mins of sun can be good but don’t overdo it
Other bad things – smoking, alcohol, processed foods

Cures / Treatments –
Collagen supplements (jury still out on benefits, but likely no harm)
Vitamin C
Retin A / Retinol (short-term benefits, but unclear on long-term)
Anti oxidants (literature is not good for longevity, except resveratrol in certain applications)
HA (hyaluronic acid)
Botox – very effective at reducing wrinkles for 6-9 months; it’s cosmetic not medical

Nails
Rate of nail growth is good indicator of aging
Decreases 0.5% per year

Hair loss
It’s strongly genetic – 600 genes involved – carried on X-chromosome
Hair follicles shrink with age
Treatments – RetinA; Rogaine; Propecia
Laser treatment has proven benefit (low laser light therapy) – likely causes hormesis and rejuvenates stem cells – similar to how infra saunas are growing in popularity

Gray hair as evolutionary indicator of experience, status – stress can induce it, and gray hair is reversible (especially in early stages)
Believes there will be products to naturally restore hair color before long

Hair starts growing in wrong places as you get older
Likely due to gene expression going awry

Eunuchs – no testes – live 14-19 years longer than the normal man (!)
In a study of 81 eunuchs, 3 became centenarians (100x greater rate than baseline)
Smaller people live longer too

All cells have fundamental same causes of aging, and similar treatment pathways

“If you keep yourself looking good, you’ll probably live longer too”