IGF-1 inhibitors and lifespan extension?

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.

Neo · 2024-05-20T16:11:02.003Z

IMG_74071179×1498 121 KB

Forbes

Is Long Life Without Disease Possible? A Rare Genetic Syndrome May Point The Way

Individuals with Laron syndrome are much less likely to suffer from age-related diseases like cancer, diabetes, and dementia. Why is that?

Virilius · 2024-05-20T16:23:55.771Z

I don’t know where I read that but doesn’t calorie restriction started in middle-aged mice not work nearly as well as it does in mice who were calorie restricted since birth?

LukeMV · 2024-05-20T16:27:07.813Z

I wouldnt be comfortable with this at all. If it were me, I would take 1-2iu of HGH per day. Every risk people bring up about a low dose of HGH has pretty much been debunked. This is not even remotely close to a bodybuilding dose. There’s no insulin sensitivity issues at this amount, especially if you’re already on an SGLT2 or Acarbose or something like that.

I really don’t think the Laron syndrome argument is the end all be all that low IGF1 is healthy. Low IGF is linked to worse cardiovascular outcomes and fixing it has shown to improve this. I doubt dwarves feel that great in their day to day lives anyway. You could probably be feeling so much better if you got that up. Optimizing hormones is criminally underrated IMO.

Bicep · 2024-05-20T16:32:13.816Z

Pretty sure HIIT will increase it by quite a bit. Google says 450% for the 24 hours after the workout.

adssx · 2024-05-20T16:37:39.753Z

Thanks; I’ll have a look. At this stage, I don’t know anything about IGF-1 and HGH, I feel like it’s yet another rabbit hole…

Neo · 2024-05-20T17:51:43.650Z

@adssx may I ask what your exercise routine is like? How much resistance training do you do? And what is your body composition/muscle mass like? (+the HIIT also)