Walk This Way to Live Longer (Backed by New Science)

Even under 8k steps might still have notable benefits.  It is convenient to walk more than 15 minutes at a time to reduce all cause mortality.

Dr. Sinclair's Protocol Updates In 2025

Comment

I take taurine, nmn, pqq, ergothioneine, urolithin a, spirulina, omega 3, magnesium, vitd+k2, hydroxytyrosol. Recently started taking nugevia resveratrol, which is best taken on a fasted empty stomach, iirc. Nugevia uses micellar resveratrol which is being tested as a resveratrol drug called Jotrol. 500mg Jotrol is said can exceed blood levels of 5g micronized resveratrol, nearly doubling them, that is it approaches levels that would take nearly 10g of expensive micronized resveratrol.

10g micronized is not just expensive but overloads system with metabolic byproducts, Jotrol can achieve the benefits of this at far lower dose without the side effects or issues of such high dose micronized.

In lemur primates, it was seen that high dose resveratrol was able to extend median lifespan over 20 percent, albeit too few primates were used to reach statistical significance in the study, and thus it was dismissed.

In fish which don't have the fast liver clearance issue seen in primates and rodents, resveratrol lengthened lifespan over 50 percent. The likely reason mice failed to show lifespan extension on resveratrol is due to fast liver clearance of resveratrol. But newer formulations promise to alleviate this issue somewhat and allow higher blood levels albeit temporarily.

If We Escape All Major Diseases, Neurodegeneration And Respiratory Failu...

Comment

Neurons were transplanted from mice to rats, and the mice neuron lived twice as long as the mice. The researchers believed that if transplanted into even longer lived animals they'd live even longer potentially indefinitely. Likely same for human. But the loss of respiratory reflex as cause of death in elderly was found in animals, and likely applies to humans too.

That is if vascular and support glia cells for neurons were kept youthful it is likely this would reduce rate of neuron death, and might allow for far longer neuron average lifespan potentially extending into two centuries or more.

That said it is true that for a real solution we do need central nervous system regeneration stem cells.

We'll Pay $101 Million If You Prove You Can Reverse Aging

Comment.

The exceptions to wear and tear, free radical oxidative stress theory of aging were explained by the membrane pacemaker theory of aging. And the exceptions to membrane pacemaker can be explained by presence of molecules such as plasmalogens that are not normally taken into account when calculating Peroxidation index. It is conceivable lowering membrane damage sufficiently would allow repair mechanisms to outclass rate of damage accumulation

NEW Japanese Walking Technique 2x Better Than 10,000 Steps

A method of interval walking where fast speed is intercalated with slow speed is mentioned.  While it has its benefits its not for everyone.  Some may prefer slow walking over long periods to any interval training using far more effort.

New upcoming resveratrol supplement

 Its called nugevia.

Appears to release in 2025

Uses a micellar technology for superior blood levels

Link to tech

https://jupiterneurosciences.com/jotrol/

Link to news on nugevia

https://www.nutraceuticalsworld.com/breaking-news/jupiter-neurosciences-launches-nugevia-supplement-line-for-longevity-and-performance/

This is very promising as way higher levels if only for limited time may enable some of the potential of resveratrol to shine through.

Resveratrol is the molecule with the strongest antiaging effects seen on cells.   Able to take old human cells and rejuvenate them to youthful state.   But the in vitro doses used are difficult to achieve or sustain in vivo due to fast clearance.

But newer formulations promise to unlock part of the potential of this molecule in vivo.

From another news article this appears to be the product website

https://nugevia.com/

Is Calorie Restriction Overrated For Longevity? @Unaging.Crissman.Loomis

Comment

The exceptions to rate of living theory were explained by membrane pacemaker theory.  Some have argued against it based on polyunsaturate composition of membranes but even here mitochondrial membrane differences and differences in other membrane molecules like plasmalogens explains these exceptions.

All in all reducing damage production explains between species differences in lifespan and also the way things like calorie restriction work.

Too severe CR is not good for humans at least Ive heard of some severe CR practitioners suffering significant bone loss.

I think 2 to 3 days of fasting mimicking diet combined with 4 to 5 days of high food based calcium intake with d3 k2 is probably good.   Food based sources like dairy, not artificial supplemental sources or fortified foods.  Artificial intake of calcium shows adverse outcomes in some studies, but not so natural food sources.

That said substances that improve mitochondrial function like urolithin a ergothioneine and pqq sound promising.  As is sources of plasmalogens or their precursors.

But with age membranes are changed such that their function worsens and they are more easily damaged.  Iirc these is due to changes in composition and the origin of these detrimental changes are unknown.  But Calorie Restriction opposes the body changing membranes in detrimental ways.  Also CR opposes many detrimental gene expression changes.  And it also has lots of good changes to parameters.

A brief comment on the membranes the membrane pacemaker theory of aging is based on membrane damage not being simple damage but the creation of autocatalytic reactive molecules able to cross both lipid and acqueous compartments damaging all parts of the cell including dna.

update:

While two long lived primate studies showed nebulous gains, another study on shorter lived primates showed massive lifespan gains from calorie restriction.  It was a lemur primate study.

Aubrey de Grey Reveals SECRET to Aging

Comment

While I like membrane pacemaker damage theory of aging, there is issues such as neurons being able to live twice as long as animals they come from, and repeated cloning being possible both without signs of aging. There is also the claim telomere lengthening rejuvenates cell and tissue level phenotype from old to young. I suspect that the damage is causing some internal clock or clocks to move and age us. Given again single cells like neurons can live twice as long as the animal and some believe can live more than ten times as long without genetic change. If repeated cloning shows dividing cells can yield youthful tissue far beyond animal lifespan and same is true for nondividing cells the body seems able to handle damage fine bar some aging clock or program interfering.

RESVERATROL - The Truth Will SHOCK You! (only on this channel!)

The benefits of the promising longevity molecule resveratrol are discussed.  Resveratrol is very promising but part of its benefits are limited in humans due to its fast clearance through the liver.  Newer formulations appear might offer promise of increasing its benefits.

Neuron Lifespan quotes and research

With neurons, nature developed biological immortality at the cellular level, but the animals needed to die to make way for the new generations, to allow for increased evolvability, or evolution rate, of the species.   Even in lowly rodents the neurons are capable of vastly outliving these short lived mammals.

“Neurons do not have a fixed lifespan,” says Magrassi. “They may survive forever. It’s the body that contains them that die. If you put them in a longer-living body, they survive as long as the new body allows them to. It increases our hope that extending lifespan will not necessarily result in brain depleted of neurons.”

https://www.nationalgeographic.com/science/article/neurons-could-outlive-the-bodies-that-contain-them

https://www.pnas.org/doi/10.1073/pnas.1217505110

Key Food to Extend Your Lifespan by 5 Years

2 minute short video on food that may increase lifespan.  Oily fish is the food that can increase lifespan by 5 years.  Omega 3 in particular seem important.

Mercury Toxicity

Symptoms of mercury toxicity are mentioned.  There's a long list of symptoms.   Mercury is very bad for health.   Things to ameliorate it are mentioned.

Comment on aging regards Gene expression vs more radical changes as pertains lifespan increases.

At least at the cellular level, it seems altering gene expression makes old cells indistinguishable from young cells in the lab under a microscope.   If you go by what Bill Andrews and Michael Fossel comment, iirc.

Some of them(Fossel, iirc) seem to believe that if gene expression is changed, the body will clear the garbage out.    The inability to process garbage locally shouldn't be too concerning, as systems like the brain have the glymphatic system that routinely exports molecular garbage out(when it malfunctions you get neurodegeneration diseases, when not you get superagers with 20 year old brain function.).   It is likely, imho, in young animals the lymphatic system plays a similar role and exports molecular garbage out of tissues.   But with aging it is compromised, and along with increased garbage production, garbage starts  to accumulate.

In human society houses don't process all of their garbage, they merely export it out for disposal or recycling, wouldn't surprise if nature does similar.   Look at the brain for example, an extremely high metabolism organ, neurons have similar metabolic costs between species, yet we live 3 times as long as bonobos who share 98% of our genes.  Our common ancestor likely had similar short lifespan, but to increase the lifespan, even tripling it, even of organs like the brain, it was mostly gene expression changes that allowed it, not novel radical mechanisms.-link to source

Longevity can be predicted by number of cortical neurons in an animal or so it seems.
https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24564

Crucially, the finding that no correlation between
maximal longevity and metabolic rate remains after accounting for
variation in numbers of cortical neurons argues strongly against
the common notion that damages accumulate at rates that scale
across species depending on metabolism (West et al., 1997).-Herculano Houzel (2018)

Interesting snippet as well as the following

While this new possibility has yet to be investigated, it
leads to one clear prediction: those species with the largest number
of cells in the relevant organ(s) will live longer before succumbing
to physiological breakdown and disintegration and,
consequently, death.-Herculano Houzel (2018)

And yet another related snippet from the news

"The data suggest that warm-blooded species accumulate damages at the same rate as they age. But what curtails life are damages to the cerebral cortex, not the rest of the body; the more cortical neurons you have, the longer you will still have enough to keep your body functional,” said Herculano-Houzel.-source 

But it seems to me that if this were the case you'd see massive lifespan reductions in indivduals with half a brain, which does occur in humans.   Otherwise this would seem to suggest aging may very well be programmed.

Paper on research on the evolution of aging, mortality

"..We created such a model to look at the evolution of intrinsic mortality, and were surprised to find the counterintuitive result that lifespan self-limitation is favored even in the absence of other conditions that could intuitively make it favorable – for instance, if animals had to stop reproducing at a certain age, or in a rapidly changing world where you needed new mutations always to be coming along to cope with the changing conditions, it would make sense to clear out old individuals and replace them with new ones." The study's key results show that even without such limiting conditions – that is, if an organism could live and keep reproducing indefinitely, and was just as adapted to the world as its offspring – the lineage would ultimately do better if genes encoded a mechanism that brings about death.

Read more at: http://phys.org/news/2015-07-death-spatial-natural-favors-genetically-limited.html#jCp

Thing is if there's an aging program, as some suspect, the possibility of radical life extension becomes more likelier, and it is believed probably would require less drastic interventions.

CR an artifact?

The most widely accepted theory is that this effect evolved to improve survival during times of famine. "But we think that lifespan extension from dietary restriction is more likely to be a laboratory artefact,"
  says Dr Adler.

Lifespan extension is unlikely to occur in the wild, because dietary restriction compromises the immune system's ability to fight off disease and reduces the muscle strength necessary to flee a predator.-link 

I would also add that since the calorie restriction is done with dense nutrient enriched optimal nutrition, this is unlikely to occur in the wild.  Without optimal nutrition calorie restriction is said to fail to extend life, small amounts of nonenriched foodsource as found in the wild is in my opinion unlikely to provide optimal nutrition required for extension. edit: especially at levels that cr can work in some animals like 60+%, at 60% deprivation not only would the nutrient density likely be insufficient, but in an environment lacking resources the small amount of calories would be insufficient for exploration, cr appears to work and extend life even in calorie amounts beyond what would be sustainable in the wild.

Ultra marathon runners could possibly see up to 16yr added lifespan

New Victorian research reveals that running long-distance runs can slow the ageing process by protecting the part of the body that stops the genes from fraying.
Runners in The Federation University Australia study had an average age of 43, but their biological age was just 27.
-link

Though previously in this blog we saw that benefits peaked at sub8mph 10miles per week and that exceeding 8mph or 20-25 miles per week could possibly damage the heart neutralizing some of the benefits.   Yet it is said that low intensity exercise does not have such a cap on adding benefits(more research is needed.), which suggest walking for most of ultramarathon distances would be optimal.   That is 10-15 miles per week with 2-3 days of resting per week at no more than 8mph and several hours of walking to achieve the ultramarathon distance.

 The findings, to be presented at the Australian Society for Medical Research National Conference, found ultra-marathon runners clocking up 40-100 km a week had 11 per cent longer telomeres.-link

Yet lifestyle changes

 Ten of the patients embarked on lifestyle changes that included: a plant-based diet (high in fruits, vegetables and unrefined grains, and low in fat and refined carbohydrates); moderate exercise (walking 30 minutes a day, six days a week); stress reduction (gentle yoga-based stretching, breathing, meditation). They also participated in weekly group support.  -link

 might allow similar benefit with much less exercise

The group that made the lifestyle changes experienced a “significant” increase in telomere length of approximately 10 percent. -link

But might not both interventions be combined and yield greater results?

Marathon improves mortality but it seems excess can wipe the benefits or does it?

 But while a study of 52,600 runners showed that pounding the pavement can yield a 19 percent lower mortality rate, that benefit was wiped out for those tallying 20 to 25 miles a week. Not exactly sure how those stats work because we all die eventually.-link

I'm planning to do about 12-15 miles per week as part of my training regimen

 ...As cardiologist Paul Thompson says in the WSJ piece, "The guys advancing the hypothesis that you can get too much exercise are manipulating the data... They have an agenda."
 ...
 Wen and colleagues reply that yes, they do have data -- and it doesn't show what O'Keefe et al. hope:
...
We were not able to identify an upper limit of physical activity, either moderate or vigorous, above which more harm than good will occur in terms of long-term life expectancy benefits...-link

It seems there are counterpoints to the arguments for moderation but still extremes should likely be cautiously avoided

Moderation seems to provide benefits with about 7mph being optimal at 10-15 miles per week with less than 7 days of running that is with resting days.

 
Regarding pace, individuals who ran six and seven miles per hour had a significant 21% and 27% lower risk of all-cause mortality, whereas those who ran eight or more miles per hour had a nonsignificant 7% lower risk of all-cause mortality.-link

There may be hope for damaged hearts

 In an act of transformation worthy of any magician, scientists have converted scar tissue in the hearts of living mice into beating heart cells. If the same trick works in humans (and we’re still several years away from a trial), it could lead us to a long-sought prize of medicine – a way to mend a broken heart.-link

Increasing membrane unsaturation with aging and longevity

It has now been documented that there is an age-associated increase in membrane PI and lipoxidation-derived molecular damage (see Table ​Table1).1). In general, PI increases during aging in an organ-dependent way.  -http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865700/

As seen on the above quote it seems that membranes peroxidation index tends to become less favorable with the passage of time, at least in some organisms.   Given that differences in membrane peroxidation index have been associated with differences in lifespan between species and within species this suggest it may be causal.

In the following we see further evidence:

The results showed significantly lower PI and lipoxidation-derived protein damage in brain and spleen from exceptionally old animals when compared to old specimens, and in a range analogous to adult animals. Therefore, low susceptibility to lipid peroxidation and maintenance of adult-like molecular lipoxidative damage could be key factors for longevity achievement.-http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865700/

 The animals that exhibited most vigorous long term survival seemed to have lower PI similar to younger adults.   While the authors suggest it may be a key to longevity, I would say it may also be a key to indefinite longevity.   It may or may not be the case that if PI is lowered enough the existing biological maintenance and repair mechanisms may be enough to grant negligible senescence.   I would predict that organisms showing negligible senescence would show such peroxidation resistance, that is they would have a lower PI and it may even be significantly lower(depending on threshold or break even point for indefinite homeostatic balance/maintenance), and a quick wikipedia search shows just that in at least one organism

 Abstract:
Summary: The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids peroxidation index (PI) is negatively correlated with longevity. Long-living marine molluscs are increasingly studied as longevity models, and the presence of different types of lipids in the membranes of these organisms raises questions on the existence of a PI-longevity relationship. We address this question by comparing the longest living metazoan species, the mud clam Arctica islandica (maximum reported longevity = 507 year) to four other sympatric bivalve molluscs greatly differing in longevity (28, 37, 92, and 106 year). We contrasted the acyl and alkenyl chain composition of phospholipids from the mitochondrial membranes of these species. The analysis was reproduced in parallel for a mix of other cell membranes to investigate whether a different PI-longevity relationship would be found. The mitochondrial membrane PI was found to have an exponential decrease with increasing longevity among species and is significantly lower for A. islandica. The PI of other cell membranes showed a linear decrease with increasing longevity among species and was also significantly lower for A. islandica. These results clearly demonstrate that the PI also decreases with increasing longevity in marine bivalves and that it decreases faster in the mitochondrial membrane than in other membranes in general. Furthermore, the particularly low PI values for A. islandica can partly explain this species' extreme longevity.

^ Munro, D., and Blier P.U. (2012). The extreme longevity of Arctica islandica is associated with increased peroxidation resistance in mitochondrial membranes. Ageing Cell 11(5): 845-55. doi: 10.1111/j.1474-9726.2012.00847.x. Epub 2012 Jul 25.-wikipedia
 

More benefits of astaxanthin

The ability of astaxanthin to inhibit the growth of colon cancer cells was studied at Catholic University School of Medicine in Rome, Italy. Astaxanthin inhibited cell growth in a dose and time dependent manner by arresting cell cycle progression and by promoting the death of cancerous cells. Astaxanthin resulted in a 220% increase in the expression of the well known anti-cancer gene p 53, and a 160% and 250% increase respectively in the anti-cancer genes p21 and p27. Astaxanthin strongly upregulated apoptosis through gene modification, and increased phosphoylation of the p38, JNK, and ERK1/2 genes by 160%, 242%, and 280% respectively. Growth inhibitory effects of astaxanthin were also observed in HT-29, LS-174, WiDr, and Sw-480 cells. These results document axtaxanthin as highly effective against colon cancer. (Cancer Letter, May 5)

Learn more: http://www.naturalnews.com/026309_astaxanthin_cancer_research.html##ixzz2sTSPBd1q

Benefits of astaxanthin.  In the particular quote we see it seems that this antioxidant exhibits anticancer activity, which is good to know as not all antioxidants seem to do so. 

 In Caenorhabditis elegans (Nematodes, used to research metabolic pathways of longevity^[37][38]), 0.1-1mM of astaxanthin is able to increase lifespan by 16-30% in all nematodes except the DAF-16 deficient ones.^[39] This enhanced lifespan was associated with increased nuclear accumulation of DAF-16 (the nuclear target of the Ins/IGF-1 signalling pathway^[40]) and increased antioxidant defenses which were thought to be due to DAF-16 gene product expression (superoxide dismutase enzymes in particular^[41]).^[39]http://examine.com/supplements/Astaxanthin/

It seems the substance can increase lifespan in some invertebrates.