Motor Units as determinants of Aging

#1

If you ever wanted aging explained to you by a wise guy, this is your opportunity - the title itself makes you look around for a hit man. If anyone knows how to stay alive, it’s Tony. I must confess I love his channel, and watch it regularly. I have - unironically - learned a lot from him.

Three Events That End You: The Real Biology of Aging (I Am Longevity)

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#2

AI Summary:

Introduction to Aging and Catastrophic Events

  • The video introduces the concept of three catastrophic events that affect every individual as they age, regardless of their health or fitness levels.
  • These events are said to occur simultaneously and contribute to why people experience a decline in health as they grow older.
  • The speaker promises to explain these events step by step, emphasizing the necessity of understanding them for maintaining vitality and youthfulness.

The 2019 Aging Study

  • A significant aging study conducted in 2019 involved measuring nearly 3,000 proteins in the blood of over 4,000 participants aged 18 to 95.
  • The study revealed that proteins are crucial indicators of health, as they reflect the condition of cells, organs, and overall bodily systems.
  • One notable finding was that scientists could accurately predict a person’s age based on protein levels, surpassing traditional biological age tests.
  • The study identified three critical age milestones at which significant biological changes occur: around ages 34, 60, and 78.
  • These age milestones are described as ‘crests’ or waves that signify major shifts in bodily functions and health.

First Crest: Age 34

  • The first crest occurs around age 34, marking the beginning of a decline in the extracellular matrix, which supports tissues, joints, and skin.
  • As the extracellular matrix weakens, it leads to a gradual loss of structural integrity in the body.

Second Crest: Age 60

  • The second crest emerges around age 60, characterized by noticeable shifts in hormones, metabolism, and circulation.
  • This shift impacts the body’s ability to regulate energy usage, blood sugar levels, and nutrient distribution, contributing to the onset of chronic diseases like diabetes and heart conditions.
  • The changes are attributed to alterations in the body’s communication systems rather than genetic predispositions.

Third Crest: Age 78

  • The final crest occurs around age 78, indicating a significant deterioration in bodily functions and systems.
  • At this stage, the body experiences a complete breakdown of circulatory systems, tissue repair mechanisms, and immune responses.
  • The study asserts that after this age, individuals enter a phase with no further biological resets, marking a critical point in aging.

Second Catastrophic Event: Loss of Motor Units

  • The second catastrophic event discussed is the loss of motor units, which begins in the mid-20s and accelerates through aging.
  • Motor unit loss is universal, affecting everyone regardless of fitness levels, and begins with the fastest type 2X fibers.
  • This decline in motor units precedes the biological changes detected in the first crest at age 34.

Timeline of Motor Unit Decline and Proteomic Changes

  • The video illustrates a combined timeline of motor unit decline and proteomic changes, highlighting how these processes unfold throughout life.
  • From birth to age 30, individuals maintain full motor unit capacity, after which the decline begins with the loss of explosive motor units.
  • The video explains that while the decline is not immediately felt, it sets the stage for further deterioration.

Incubation Period: Ages 40 to 60

  • Between ages 40 and 60, known as the incubation period, the loss of motor units becomes more apparent as recovery times lengthen and physical discomfort increases.
  • During this time, silent health issues like high blood pressure and cardiovascular diseases begin to develop, often without obvious symptoms.
  • The decline in motor units affects overall bodily functions, including metabolism and hormonal regulation, leading to accelerated aging processes.

Critical Changes from Ages 60 to 80

  • Ages 60 to 80 represent a crucial phase where the second major protein wave impacts hormones, metabolism, and circulation.
  • During this period, motor unit loss accelerates sharply, with significant declines observed by age 70.
  • The video highlights the phenomenon known as “falling off a cliff,” where health and functional capacity rapidly deteriorate around age 75.

The Cliff Phenomenon

  • The cliff phenomenon describes a sudden decline in health and functioning, where individuals may experience drastic changes in their physical capabilities.
  • This phenomenon is illustrated by data showing a steep drop in both muscle mass and physical activity levels after age 75.
  • The video notes that this decline is not confined to any specific group, as even top athletes experience this sudden loss of performance.

Survival Mode: Ages 80 to 100

  • From ages 80 to 100, individuals enter a survival mode characterized by a rapid loss of motor units and increased frailty.
  • Most individuals do not die from specific diseases but rather from the overall weakness that accompanies advanced age.
  • Neuromuscular studies confirm that muscle responsiveness and speed decline significantly after age 80, leading to increased risks of falls and injuries.

The Role of Motor Units in Aging

  • The video emphasizes that the loss of fast type 2X motor units is a critical factor in the aging process, occurring as early as the 20s.
  • Individuals classified as survivors, delayers, or escapists still face the inevitable decline associated with motor unit loss.
  • The speaker stresses that no interventions can reverse the loss of motor units, which fundamentally limits human life.

Conclusion and Call to Awareness

  • The speaker concludes by urging viewers to recognize the reality of aging and the importance of understanding the biological processes involved.
  • He warns against complacency in youth and emphasizes that true aging challenges become evident after age 75.
  • The message is clear: awareness of these aging processes is crucial for preparing for the inevitable changes in health and function.
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#3

He’s talked about it (“motor units”) before. I remember just a few months ago there was a chat about “motor units” between Stanfield, Carvalho, and Verhoven, and they didn’t bother to mention this guy. I actually subscribed to his channel a while back, but he’s a bit cocky and overly critical of Michael Lustgarten (and others). Still, I think there’s value in some of the things he says. He’s clearly in very good shape for someone in their 60s, which is unusual.

I vaguely recall a while back that there were discussions about various supplements that dramatically reduce risk / problems of declining motor unit functioning. If memory serves, one of them was melatonin – but I could be wrong.

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#4

He’s good on the subject of motor units and exercise but I dislike his excessive pessimism of what we might be able to do about aging. He just says “you will die by 120 there nothing you can do. Science will never figure out how to fix the motor unit problem”

It’s like he’s just rage baiting.

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#5

I have not looked at the details behind the video above, but this sounds like mRNA splicing changes.

#6

Deleted by author.

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#7

I have seen Peter Fedichev and other scientist mentioned 120 years as an upper limit of our age, there are few mathematical models that proves this.

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#8

I know but it is a pointless thing to just say 120 is the limit and nothing that we ever innovate with will ever change that. We may as well try.

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#9

I am the person in the video, and I just read the comments here. That is correct, no one will ever go near 120 unless you find a way to slow the loss of motor units… Got bad news for all of you. There is nothing on this planet that can slow the loss of motor units. Nothing cocky about me. I tell it like it is.

You all better start waking up. There are no magic pills!!! Apparently, most of you are too naive and ignorant to understand.

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#10

There is nothing cocky about me… I back up everything with evidence. And yes, Lustgarten is not going anywhere, and he sure will not conquer aging. If you move like an old man at 50, you are not going anywhere near 120. What’s the matter, you do not like that I expose these people???

#11

Tony, thank you for your videos, like I said, I really did learn a lot from you, and you provided a lot of backup with scientific papers, so you’re the real deal. That said, I would not be 100% certain that it’s impossible to slow down or maybe even arrest the loss of motor units. Joanne Mannick when she was still at Tornado, showed very interesting research on mTOR inhibitors stopping the loss of muscle innervation robustly in older animals (in mice). We are getting closer to solving the problems, including loss of motor units. I’m not saying it’s going to happen tomorrow, but science progresses, and I believe one day we’re going to solve this.

Now, I am not a fan of the idea that there’s going to be “exercise in a pill” - I don’t believe that, and I’ve written before many times why that is impossible. But I believe that a good exercise program PLUS the right drugs may one day preserve optimal muscle function, so an 85 year old can have the muscles of a well trained 25 year old. This is the goal. When that happens I don’t know, but one day it will, because science always marches forward. The people on this site are dedicated to the idea that science can get us better lifespan and healthspan than ever before in history. Progress is frustratingly slow, but science is our only hope, and we believe more knowledge is always better - which is why I linked to your channel because you provide a lot of valuable knowledge. Be well, and all the best!

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#12

The mantra of every nutcase trying to make an argument.
The mantra of losers that can’t make an argument without name-calling.

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#13

Ok so we can find ways of addressing the loss of motor units. I see you saying there is nothing that can ever be done about it. You don’t know the future. No one does. If you think it’s that vital, you should be doing everything to get new treatments for motor units! I’d support it, I just don’t support the fatalistic attitude towards the future.

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#14

Nutcase, eh? I’m sorry, but if at 61 with 4% body fat, and literally move like a 25-year-old NFL running back makes me a nutcase, what does that make you in your old, aged body? See, you fantasize about what ifs while I show!!! How is that for nutcase???

#15

Dealing moreso with the science than the unnecessary abuse, it appears that motor neurons die off with them losing their axons and the body fails to replace them. In essence it is a lower scale type of sort of slowish ALS/MND. It is the sort of thing that would happen with age related mitochondrial damage. Hence fixing it is the same issue.

#16

Apparently, you didn’t see the pictures of my 84-year-old body on another thread.
I doubt you will look that good at 84. One wonders if you are off your meds, or just another case of bodybuilder roid rage. By the way, 4% body fat is unhealthy and increases all-cause mortality.

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#17

I think you’re mixing two very different biological realities.
Mitochondria are not comparable to motor neurons. Mitochondria are dynamic organelles; they undergo constant turnover through biogenesis and mitophagy. If damaged, they can be replaced, multiplied, and their function can be restored.

Motor neurons, on the other hand, are “terminally differentiated and post-mitotic”. From birth, you get your lifetime allotment. They cannot divide, cannot regenerate, and once they die, the entire motor unit they control is permanently erased.

So mitochondrial decline is, at least in part, reversible and adaptive. Motor neuron loss is not. That’s the crucial distinction. My next video is going to explain all this. Maybe you should read my published preprint study because I clearly show that mitochondria have absolutely no standing against motor units (https://doi.org/10.31219/osf.io/hw8v7_v1)

#18

So, I name-call and you make childish and false accusations? And you are 84? And you say I will not look like you at 84? I do not know what you look like. You are hiding like everyone who compares themselves to me. One thing is certain. You are a frail old man.

As I said, you are very ignorant. I prove and show what I speak about. You literally are too slow to understand it. More than likely it is the grey and white matter that has shrunk by at least 40% in your brain. You already lost most of your motor units.

You then say I am on meds? How funny is this? projecting, eh? I take no meds, frail old man!!!
And you actually have the cohones to compare yourself to me? Show yourself

You sound like one of those little girls in elementary school, literally!!!

#19

The following paper looks at how (altered) mitochondria (which are organelles and found in all cells apart from red blood cells) are part of causing Motor Neuron diseases.

Hence you are in one sense right to say “Mitochondria are not comparable to motor neurons.” That is because you find mitochondria in neurons (including motor neurons).

It is, however, the mitochondrial deterioration that causes the motor neuron failure. Hence maintaining mitochondria will maintain motor neurons. Although the body can compensate in a limited way to motor neuron failure, there is no currently identified mechanism that reliably replaces them. Hence what is the priority is maintaining mitochondrial function.

My guess is that there will be some mechanism possible linked to HIF 1 alpha and possibly requring exogenous stem cells that it might be possible to find to do this, but we don’t have that today and it is best therefore to assume it won’t be available.

#20

You do not seem to get it. Motor unit loss happens decades before anyone has any type of mitochondrial problems. You are incorrect. You start losing motor units around the age of 18, and even if you are healthy!!!