IGF-1 inhibitors and lifespan extension?

DeStrider · 2023-09-05T22:30:23.271Z

Methionine activates MTOR and inactivates AMPK. It’s kind of the anti-Rapamycin. So it makes sense that reducing it would extend life expectancy.

PubMed Central (PMC)

Methionine Supplementation Affects Metabolism and Reduces Tumor...

Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is...

Neo · 2023-09-06T01:33:24.583Z

Thanks @RapAdmin for of this valuable info, very helpful and valuable!

RapAdmin:

Rapamycin “should” lower IGF-1 according to the research, but I wonder by how much / how dose-responsive it is…

Has anyone measured and seen how IGF-1 changes with rapa N=1?

Neo · 2023-09-06T01:35:57.128Z

RapAdmin:

These people don’t get cancer, and are very low on the scale for other age related disease: diabetes, and cognitive decline.

This really fits with things I’m trying to find and create strategies for - cancer and neurodegen as 2 of the bid 4 seems so much less under our control than cardiovascular and metabolic disease…

Neo · 2023-09-06T01:46:30.445Z

RapAdmin:

I’ve had it tested, but don’t do it very often (its not one of my main biomarkers I track) - but perhaps it should be.

That’s what I’m thinking.

From LEF it seems that:

“IGF-1 appears constant over a 24-hour period, making it useful as a bio-marker to help assess blood levels of GH.”

And

”Fasting is not required for this test. Take all medications as prescribed.”

And from Marek it seems like it one the tests that (at least with some assays) can get wacko results if done while having somewhat recent vitamin B7 supplementation:

”Note: This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin. Cease biotin supplementation at least 72 hours prior to blood draw.”

RapAdmin · 2023-10-11T05:11:31.097Z

all about growth hormone:

Neo · 2023-11-28T19:24:01.904Z

RapAdmin:

I’ve had it tested, but don’t do it very often (its not one of my main biomarkers I track) - but perhaps it should be.

Here are my test results. Seems that as long as I keep working on muscle and resistance training as a foundation against osteoporosis and sarcopenia and I’m not worried about those then lower might be even better?

IMG_64031179×2556 190 KB

RapAdmin · 2023-12-19T21:48:34.604Z

Joseph_Lavelle:

Perhaps this is one of those stuck-in- growth mode things that rapa and CR helps with.

Yes - hyper function theory of aging, and antagonistic pleiotropy all wrapped up in one

en.wikipedia.org

Pleiotropy | Antagonistic pleiotropy

Sometimes, a pleiotropic gene may be both harmful and beneficial to an organism, which is referred to as antagonistic pleiotropy. This may occur when the trait is beneficial for the organism's early life, but not its late life. Such "trade-offs" are possible since natural selection affects traits expressed earlier in life, when most organisms are most fertile, more than traits expressed later in life. This idea is central to the antagonistic pleiotropy hypothesis, which was first developed by G....

Hyperfunction theory of Aging:
https://www.aging-us.com/article/203937/t

EnrQay · 2024-02-19T01:12:59.139Z

After taking rapamycin for a couple of years, I am on a 2 month break that probably ends in March. Before I restart, I’ll report on my IGF-1 as a baseline and get it remeasured three months after that. Any problems with allowing 3 months to establish a possible change in results?

EnrQay · 2024-03-06T14:02:52.689Z

My test results, after a 2 month layoff of rapamycin, followed by 4mg rapamycin with 10oz grapefruit on a Friday, then the IGF-1 test on Monday: 74ng/mL (reference: 68-247). I’m in the 25th percentile as a 60yo male, which sounds good to me for longevity purposes. I’ll test again after a couple of months of intermittent rapamycin.

2-Figure1-11014×1032 90.6 KB

from https://www.semanticscholar.org/paper/Serum-insulin-like-growth-factor-I-in-diabetic-Payne-Tangpricha/54e1e0d8f03c06b328df601e60028999553ee658

According to this:
THE HYPOTHALAMUS AND PITUITARY PART II

plasma half-life of IGF, which is around 12 h

so perhaps at least part of my lower-but-normal IGF-1 is due to the rapamycin 3 days earlier.

RapAdmin · 2024-04-09T18:45:36.310Z

New Open Access Paper Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans by Elizabeth M. L. Duxbury & AlexeiMaklakov et al.

Full PDF paper: Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans

adssx · 2024-05-20T13:26:39.951Z

I got my IGF-1 tested for the first time (thanks @Neo, for suggesting it): 40.3 ng/mL, so very low

I’m struggling to understand whether this is good or bad…

Neo · 2024-05-20T14:31:29.668Z

Yeah. It’s like free testosterone levels…. low might be best for longevity, medium might be better for (current) healthspan

… my personal goal is to maximize longevity while keeping current health status good, so rather lower than higher on IGF-1…., but seems tough to triangulate in on what exactly is optimal from the different data types that we currently have

Perhaps look into what things could be negative and make sure you don’t see any symptoms related to those.

Any idea why it might be low? I haven’t looked into it, but perhaps SGLTi nudges it down?

adssx · 2024-05-20T15:00:30.652Z

Neo:

Any idea why it might be low? I haven’t looked into it, but perhaps SGLTi nudges it down?

No idea. SGTLi don’t seem to have an effect on IGF-1. Weird: ARBs might increase it: AT1 receptor blockers increase insulin-like growth factor-I production by stimulating sensory neurons in spontaneously hypertensive rats 2009 (not sure if it’s a good paper).

Symptoms are very non-specific: https://www.testing.com/tests/insulin-growth-factor-1-igf-1/

In adults, abnormally low levels of GH and/or IGF-1 may cause subtle, nonspecific symptoms such as:
Decreased bone density
Fatigue
Adverse lipid changes
Reduced exercise tolerance
Depression
Thinning, dry skin

Neo · 2024-05-20T15:01:27.002Z

EnrQay:

Before I restart, I’ll report on my IGF-1 as a baseline and get it remeasured three months after that.

Curious, do you have any update on this?

Neo · 2024-05-20T15:03:25.215Z

adssx:

abnormally low levels

What is the range of your test? (Your level seems just outside of the edge of the “normal” range from Quest Labs)

EnrQay · 2024-05-20T15:22:47.414Z

I’m not sure if you saw my posted results above. I’m not planning to do another test any time soon.

Neo · 2024-05-20T15:24:59.624Z

@EnrQay Sorry. Don’t seem to see anything after your message in Feb on having new OmegaQuant tests planned - am I missing that info somehow?

adssx · 2024-05-20T15:34:05.423Z

Neo:

What is the range of your test? (Your level seems just outside of the edge of the “normal” range from Quest Labs)

They give 79–900 ng/mL as the “normal” range. They write:

Many factors can lead to having low IGF-1 levels such as: nutritional deficiencies, disorders of the pituitary gland, aging, kidney disease, liver disease, elevated estrogen.

Neo · 2024-05-20T15:43:03.141Z

FWIW: Quest has 52 as lower range of “normal”

Perhaps good to include now and then in future so you can build a time series

EnrQay · 2024-05-20T16:00:19.898Z

here you go:

IGF-1 inhibitors and lifespan extension?

My test results, after a 2 month layoff of rapamycin, followed by 4mg rapamycin with 10oz grapefruit on a Friday, then the IGF-1 test on Monday: 74ng/mL (reference: 68-247). I’m in the 25th percentile as a 60yo male, which sounds good to me for longevity purposes. I’ll test again after a couple of months of intermittent rapamycin. [2-Figure1-1] from https://www.semanticscholar.org/paper/Serum-insulin-like-growth-factor-I-in-diabetic-Payne-Tangpricha/54e1e0d8f03c06b328df601e60028999553ee658 According to this: THE HYPOTHALAMUS AND PITUITARY PART II plasma half-life of IGF, which is around 12 h so perhaps at least part of my lower-but-normal IGF-1 is due to the rapamycin 3 days earlier.