Aging: What is it & How to Slow, Reverse and Measure it
Live Longer World Podcast Season 1 Recap
That was a wrap on Live Longer World Podcast Season 1.
In the last few months, I’ve released 17 podcasts episodes where I’ve had conversations with scientists & entrepreneurs on topics ranging from longevity supplements, to how scientists think of aging, to rejuvenation therapies like blood plasma dilution and epigenetic reprogramming.
Below is a recap on the episodes grouped by topic, so you can listen to whichever topics pique your curiosity. Where helpful, I provide a brief summary of the arguments presented under each topic and if you wish to dive deeper into them, you can watch / listen to the entire podcast episode linked by category. Timestamps are also available in the show notes and YouTube versions of the podcast.
For those who are new to the realm of longevity science and aging, this post also hopes to serve as a primer or introduction into some of the areas being investigated in the field. This is certainly not a comprehensive snapshot of all the topics being explored in the field; it’s simply a summary of the topics that have been covered so far on the podcast, but over the next few months I hope to make this library more extensive as I release more podcast episodes. Stay tuned for that!
Before I lay out the topics / categories covered and provide summaries for each, I want to say that if you are completely new to aging and longevity science, you might want to read my post Why Longevity Science is Relevant To You for some more context around this recap post.
Topics / Categories Covered:
What is Aging?
Aging in Different Organs
How to Slow / Reverse Aging
How to Measure Your Biological Age
Diseases of Aging
Model Organisms for Aging
What is Aging?
Aging is Damage Accumulation:
This view of aging as damage accumulation is essentially saying that with time, we accumulate damage and this damage manifests itself in different ways such as knees faltering, hair turning white or more severe cases like kidney failure.
Reason, the first guest on my podcast, gives the analogy of a rusting car. Similar to how a car accumulates rust with time, we accumulate damage and dysfunction with time.
Podcast Reference: Reason, CEO Repair Biotech | How to Fight Aging, NAD+ Boosters, Senolytics & Curing Atherosclerosis
Aging is Functional Decline:
How well is our immune system functioning? How well is our brain or heart functioning? What about walking speed and grip strength?
With age, there comes a decline in functional measures such as those measured above and Matt Kaeberlein talks about how we need to think of aging not just from a biological perspective, but also from a functional decline perspective.
Let’s be clear Matt is saying that we still need to understand aging from a molecular perspective to come up with interventions for aging, but once we have interventions we need to test them against functional measures. Are the interventions actually improving functional measures of aging because if they are merely increasing lifespan without any benefits to functional quality of life, then they aren’t as useful.
Podcast Reference: Aging Interventions - Rapamycin, NAD+ & Dog Aging Project | Matt Kaeberlein
Aging is slowdown in repair machinery:
Aging is not simply wear and tear and damage but its a balance between damage and repair. So those who can repair the damage better live better. The Conboy’s give the example of a squirrel and rat. They are similar animals with similar size and metabolism. But squirrels live between 20-30 years whereas rats live only 3 years.
The capacity to repair the damage is causing aging at different rates.
Podcast reference: Rejuvenation Via Plasma Dilution, Parabiosis & Neutral Blood Exchange | Dr. Irina & Michael Conboy
Aging is DNA damage:
“DNA is the blueprint of life..And it’s really surprising how unstable the DNA is. It inflicts tens of thousands of lesions every single day. Every single cell in our body experiences about a 100,000 DNA lesions everyday, so it’s constantly occurring. It’s a fact of life that DNA is damaged and requires constant repair. And there are distinct repair mechanisms and when they fail people can age in an extremely accelerated fashion."
Podcast reference: DNA Damage & Aging | Dr. Bjorn Schumacher
Aging is Epigenetic Changes (Strong epigenetic theory):
Yuri’s Strong Epigenetic Theory of Aging: Epigenetic changes are kind of happening by themselves. They're not a reaction to something, they're essentially an implementation of a life history. Pre-programmed for a given organism with set time points that just take place because of that's how the organism is set up. So epigenetics is actually driving those changes.
By contrast, Weak Epigenetic Theory of Aging: Epigenetic changes during age are reacting to DNA damage or some other process that breaks down during age
Podcast reference: Epigenetic Reprogramming, Cryonics & COVID Lab Leak | Yuri Deigin
Aging is hyperfunction or programmatic or quasi-programmed:
Growth is driving aging. Aging is not programmed, it’s a byproduct of evolution. But the word programmed is complex. Programmed can mean programmed in mechanistic sense not necessarily in the adaptive sense.
Aging is quasi-programmed. Programs that have evolved to be functional in early life, they run on in later life in a way that is essentially futile. You have an adaptive program that runs on to become a pathogenic adaptive program.
David Gems also critiques the hallmarks of aging and says that aging is not entirely understood by just the hallmarks of aging - there is more to understanding aging outside of the hallmarks.
Podcast reference: Hyperfunction & Programmatic Theory of Aging and Critique of the Hallmarks of Aging | Dr. David Gems
Aging is evolutionary:
Your genes are replicators (Richard Dawkins evolutionary theory) and they want to replicate. They want to be passed on from generation to generation. If we take the viewpoint that our genes only care about replication, they will keep us healthy till we are able to successfully reproduce and pass on our genes to our offspring. After this point, they don’t care so much start to accumulate damage and age.
Aging from an Evolutionary perspective | Reason, the founder & CEO of Repair Biotechnologies
My Remarks:
Yes, different scientists have different theories on aging. Aging is likely multi-faceted though so it could be a combination of a lot of these theories and more. Scientists are mostly trying to identify the major causes of aging when they come up with different theories. While some of them like Matt Kaeberlein think that we won’t necessarily converge on one theory of aging and that is okay because we only need to find interventions for it, others like Vadim Gladyshev believe that we should understand aging otherwise we won’t be able to tackle it.
Aging in Different Organs
Brain Aging:
Brain aging might be one of the most difficult and complicated areas of aging to comprehend. This is likely got to do with the fact that we understand very little about the brain and not knowing basic research on the brain impedes our ability to study aging in the brain. But, it’s also one of the most important areas to work on since the brain controls most of our functions and no one likes the slowdown in the brain’s processing capacity and creativity with age.
Jean Hebert is one of the foremost researchers studying brain aging and neuroplasticity. He thinks that plasticity is transferable in the sense that if one area of the brain gets damaged, it transfers the information to another area. As such, if we replace damaged parts of the brain, we can still retain our old memory. Jean also has a radical approach to beat aging whereby he thinks that the only way to truly beat aging is whole body and tissue replacement along with replacing the brain.
Podcast reference: Dr. Jean Hebert | Brain Aging, Tissue Replacement & Radical Strategy to Fight Aging
Cellular Senescence:
Cellular senescence is a process in which cells lose their ability to divide but refuse to die. When these senescent cells don’t get cleared away, they release harmful substances and damage the cells around them too. It is widely regarded that senescent cells accumulate with age, contributing to inflammation and aging itself. Senolytics is a class of drugs that can selectively clear away these senescent cells and they have shown promise in delaying and preventing age-related diseases.
Cellular senescence comes up a lot in aging research and a few of my guests have discussed it with respect to cancer, skin aging, and overall aging. Note that there are some guests who also think the evidence for cellular senescence contributing to aging is not as robust.
Podcast reference: Cancer, Cellular Senescence & Senolytics | Dr. Peter Adams
Skin Aging:
Carolina Oliveira believes that the skin has been overlooked in aging research even though skin is the largest organ in the human body. There is accumulation of damaged senescent cells in skin as well, and Carolina’s company OneSkin focuses on creating topical creams to slow down the accumulation of senescent cells.
Podcast reference: Skin Aging for Longevity; OneSkin
Collagen / Extracellular Matrix (ECM) Aging:
The ECM is the environment that surrounds the cell or the proteins secreted from the cell. It holds our organs and tissues in place. You’ve probably heard of collagen protein - it is largely found in the ECM.
Why is the ECM relevant for longevity research? Turns out, the ECM changes with age. In fact, each cell has a unique ECM and cancer cells can be detected by their ECM composition type! There is also a connection between the ECM and the muscle, and damage to collagen with age results in weakening of our muscles.
Podcast reference: Collagen Protein & the ExtraCellular Matrix During Aging | Dr. Collin Ewald
Mitochondria Aging:
The mitochondria is a hot target for aging research. Dysfunction in the mitochondria with age has been linked to several diseases including Parkinson’s. Of course, one way to improve the health of your mitochondria is to exercise! But scientists are better trying to understand how changes in mitochondria occur and how they contribute to aging.
Podcast reference: Mitochondrial Dysfunction & Parkinson's Disease | Andy Lee, COO Vincere Biosciences
How to Slow / Reverse Aging?
In my view, there are 3 broad buckets to classify ways to slow and reverse aging: Lifestyle practices, Longevity Supplements, and Rejuvenation Therapies
Lifestyle Practices:
This is the low-hanging fruit in the sense that everybody knows that healthy lifestyle practices lead to a healthier life. It is not low-hanging in the sense that it’s easy for people to implement, but if you truly wish to improve your health, I’m confident you will find a way to exercise, sleep well, eat healthy etc. I’ve written longevity lifestyle posts on exercise, what I eat, supplements, sleep and so on and you can find all of it in the post Optimize Your Health in 2022.
Longevity Supplements:
Longevity supplements always receive the most hype partially because it’s easy for people to experiment with them, partially because a lot of labs focus on them, and partially because people think it’s magical to be able to slow aging by popping in pills. Some of them have promise, some of them might be hyped and often different scientists might have different opinions too. I’m bringing to you what scientists say about some of these supplements such that you can decide for yourself based on the available data. Here is a list of supplements discussed in Season 1 so far with podcast references:
NAD+ boosters like NMN and NR:
Rapamycin (IMHO probably one of the most promising candidates!):
Metformin: Centenarian Longevity & Metformin | Dr. Nir Barzilai
Alpha-Ketoglutarate (AKG): Aging Networks & Biomarkers, Alpha-Ketoglutarate & Longevity of Bats | Dr. Brian Kennedy
Spermidine: Brian Kennedy | Spermidine for Autophagy & Combining Longevity Supplements
Urolithin A: Aging Networks & Biomarkers, Alpha-Ketoglutarate & Longevity of Bats | Dr. Brian Kennedy (40:07)
Senolytics like Quercetin / Fisetin: Cancer, Cellular Senescence & Senolytics | Dr. Peter Adams
Collagen: Collagen Protein & the ExtraCellular Matrix During Aging | Dr. Collin Ewald
Rejuvenation Therapies:
When I speak of rejuvenation therapies, I speak of therapies that have chances of reversing a lot of the damage and hence lowering our biological age. In contrast, most supplements might only slow damage accumulation, and not reverse it. More data needs to be out to determine the validity of my statement, but for the purposes of this post, I’m going to call the following methods rejuvenation therapies:
Epigenetic / Partial Reprogramming:
Shinya Yamanaka (Nobel Prize in Medicine in 2012) discovered the Yamanaka factors that can turn back the cell to its young state again, or in other words, it can rejuvenate the cell. So Epigenetic reprogramming is using this information. But we only want partial reprogramming, so you want to restore some youthful function, but not turn the cell back to pluripotent state. And this is because, if the cell is completely rejuvenated, then it might lose its identity, which increases the risk of cancer and will die. Hence, the concept of partial reprogramming: What if we could do a little bit of reprogramming without turning back the clock fully and get the benefits of rejuvenation and still have a functional cell?
Podcast reference: Epigenetic Reprogramming, Cryonics & COVID Lab Leak | Yuri Deigin
Neutral Blood Exchange / Plasma Dilution:
Neutral blood exchange research was pioneered by the Conboy’s and their work is groundbreaking. They showed how plasma dilution and replacing half of the blood plasma with a mixture of saline and albumin reverses signs of aging and rejuvenates muscle, brain and liver tissue in old mice. Highly recommend this podcast.
Podcast reference: Rejuvenation Via Plasma Dilution, Parabiosis & Neutral Blood Exchange | Dr. Irina & Michael Conboy
How to Measure Your Biological Age
There are several clocks being developed to allow you to measure your biological age and see which interventions are working. The problem is that a lot of these clocks are not robust or consistent and some of the consumer ones are quite expensive too. However, new work on these clocks is trying to make them more robust and detailed. In particular, I highly recommend my podcast with Dr. Morgan Levine to learn more about the biological clocks that were being developed in her lab.
DNA Methylation & SystemsAge Clock: Morgan Levine | Epigenetic Clocks, SystemsAge Clock, Epigenetic Reprogramming
BiT Clock / Transcriptomic clock being developed in Dr. Bjorn Schumacher’s lab: DNA Damage & Aging | Dr. Bjorn Schumacher
Model Organisms for Aging
When it comes to humans, centenarians are the model organisms for aging and Dr. Nir Barzilai has done some extensive work studying longevity in centenarians. Other organisms that have come up in the podcast either for their longevity or for studies being done on them are bats, dogs, naked mole rats.
Centenarian Longevity: Centenarian Longevity & Metformin | Dr. Nir Barzilai
Bat Longevity: Aging Networks & Biomarkers, Alpha-Ketoglutarate & Longevity of Bats | Dr. Brian Kennedy (41:55)
Dog Aging Project: Dog Aging Project: Longevity and Rapamycin Studies in Pet Dogs | Matt Kaeberlein
Are naked mole rats a good model organism? Rejuvenation Via Plasma Dilution, Parabiosis & Neutral Blood Exchange | Dr. Irina & Michael Conboy (2:55)
Diseases of Aging
A few different diseases of aging have been discussed on the podcasts. These include Cancer, Atherosclerosis, Alzheimer’s, Parkinson’s disease.
Atherosclerosis: Reason, CEO Repair Biotech | How to Fight Aging, NAD+ Boosters, Senolytics & Curing Atherosclerosis
Cancer: Cancer, Cellular Senescence & Senolytics | Dr. Peter Adams
Alzheimer’s: Morgan Levine | Epigenetic Clocks, SystemsAge Clock, Epigenetic Reprogramming (1:05:20)
Parkinson’s: Mitochondrial Dysfunction & Parkinson's Disease | Andy Lee, COO Vincere Biosciences
Concluding Remarks:
I hope this recap of Live Longer World Podcast Season 1 by topic was helpful to you. Some exciting news: Season 2 will be starting next week and I already have some amazing guests and podcast episodes I’m very excited to share with you. In the meantime, you can find the entire library of podcasts below and subscribe wherever you listen to your podcast. Stay in good health - Aastha.