#55

So through Access Labs (through Labcorp) IGF-1 is $20, but needs a doctor’s order. I however learned about a new test IGF-BP-3 which is $29 through them … and here is some information on it.
https://endocrinology.testcatalog.org/show/IGFB3

I guess I usually use IGF-1 as a measure of how much ongoing growth vs. not is going on and I like to see people around the average for their age. This particularly comes up when I have patients wanting to push their GH/Testosterone etc. With some trepidation, if the IGF-1 isn’t getting stimulated, it’s possibly okay - but at the point this is going off, I warn them they are expediting death.

On the other side of things, an IGF inhibitor might make you live longer, but possibly in a fashion in which you’d not enjoy living?

Anyway, this test IGF-BP3 is an interesting addition, no sure how/when to use it yet. Any experience or thoughts on this?

6 Likes
#56

Thanks. These are good questions to which I don’t have an answer but my guess is that signaling (number of receptors and their sensitivity) might be more important than the quantity of IGF-1 itself.

What about rapamycin? It lowers IGF-1 levels but does it impact the signaling as well?

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#57

If the optimal range for longevity is based on your current age, this makes things even harder…

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#58

A GH/ IGF-1 lowering drug has gone generic so should be available soon from Indian suppliers… (should you want to lower your GH/IGF-1 for longevity purposes).

Cipla receives final approval for the generic version of Somatuline® Depot (Lanreotide) Injection

MUMBAI, India and WARREN, N.J., May 22, 2024 /PRNewswire/ – Cipla Limited (BSE: 500087; NSE: CIPLA EQ; and hereafter referred to as “Cipla”) and its wholly owned subsidiary Cipla USA Inc., (hereafter referred to as “Cipla”), today announced that it has received the final approval for its Abbreviated New Drug Application (ANDA) for Lanreotide Injection 120 mg/0.5 mL, 90 mg/0.3 mL, 60 mg/0.2 mL from the United States Food and Drug Administration (USFDA).

Cipla’s Lanreotide Injection is AP-rated therapeutic equivalent generic version of Somatuline® Depot (Lanreotide) Injection. Lanreotide Injection is supplied as 120 mg/0.5 mL, 90 mg/0.3 mL, 60 mg/0.2 mL single-dose, pre-filled, ready-to-inject syringe. Cipla’s Lanreotide injection is indicated for the treatment of patients with Acromegaly and Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs).

According to IQVIA (IMS Health), Somatuline® Depot (Lanreotide) had US sales of approximately $898M for the 12-month period ending March 2024.

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#59

Here is an interesting question… I wonder if targeted delivery of IGF-1 (into skin via mesotherapy, etc.) or muscle (IM injection), etc. might be beneficial when done on a pulsed dosing schedule. This would avoid the systemic issues of IGF-1 delivery, while maintaining some of the benefits of IGF-1?

A new review paper that got me thinking about this:

Endocrine Controls of Skin Aging

Skin is the largest organ of the human body and undergoes both intrinsic (chronological) and extrinsic aging. While intrinsic skin aging is driven by genetic and epigenetic factors, extrinsic aging is mediated by external threats such as UV irradiation or fine particular matters, the sum of which is referred to as exposome. The clinical manifestations and biochemical changes are different between intrinsic and extrinsic skin aging, albeit overlapping features exist, eg, increased generation of reactive oxygen species, extracellular matrix degradation, telomere shortening, increased lipid peroxidation, or DNA damage. As skin is a prominent target for many hormones, the molecular and biochemical processes underlying intrinsic and extrinsic skin aging are under tight control of classical neuroendocrine axes. However, skin is also an endocrine organ itself, including the hair follicle, a fully functional neuroendocrine “miniorgan.” Here we review pivotal hormones controlling human skin aging focusing on IGF-1, a key fibroblast-derived orchestrator of skin aging, of GH, estrogens, retinoids, and melatonin. The emerging roles of additional endocrine players, ie, α-melanocyte-stimulating hormone, a central player of the hypothalamic-pituitary-adrenal axis; members of the hypothalamic-pituitary-thyroid axis; oxytocin, endocannabinoids, and peroxisome proliferator-activated receptor modulators, are also reviewed. Until now, only a limited number of these hormones, mainly topical retinoids and estrogens, have found their way into clinical practice as anti-skin aging compounds. Further research into the biological properties of endocrine players or its derivatives may offer the development of novel senotherapeutics for the treatment and prevention of skin aging.

Paywalled article:

https://academic.oup.com/edrv/advance-article-abstract/doi/10.1210/endrev/bnae034/8029650#google_vignette

2 Likes
#60

I think that’s a plausible solution.

#61

IGF-1 Expression in Skin Can Drive Age-Related Hair Loss

Aging is an accumulation of damage and dysfunction, but a quite specific collection of forms of damage and dysfunction. One can create conditions that look like premature aging, or very selective forms of premature aging of specific tissues and organs, with any number of damaging interventions, such as administration of toxins or altered expression of genes. These are not aging. Just because an intervention produces dysfunction and damage that looks like aging doesn’t necessarily mean that it has any relevance to normal aging. The details matter. It is worth remembering this point.

In today’s open access paper, the authors report on their discovery that artificially increased expression of IGF-1 in skin produces accelerated aging of hair follicles by encouraging cellular senescence. Clearing out the senescent cells or interfering in downstream targets of IGF-1 reverses this effect, restoring hair follicle function. None of this implies that IGF-1 signaling is in any way a useful target in the normal aging of hair follicles, even given that reducing IGF-1 signaling is a well studied topic when it comes to slowing aging in short-lived species, and even given evidence for increased IGF-1 signaling in skin with age. Any approach to induce greater cellular senescence in a specific cell population is going to harm its function, and there are many, many ways to go about this, few of which are relevant to cellular senescence in normal aging. To close the loop for this paper, the researchers would need to show that the treatments that work in their model of increased IGF-1 signaling also work in old mice, but they did not do that.

Targeting IGF1-Induced Cellular Senescence to Rejuvenate Hair Follicle Aging

The insulin-like growth factor-1 (IGF-1) signaling pathway is known as a potent aging modifier, disruption of which consistently associates with lifespan extension across diverse species. Despite this established association, the mechanisms by which IGF-1 signaling modulates organ aging remain poorly understood. In this study, we assessed age-related changes in IGF-1 expression across multiple organs in mice and identified a more prominent increase in skin IGF-1 levels with aging - a phenomenon also observed in human skin.

To explore the consequences of elevated IGF-1, we developed transgenic mice ectopically expressing human IGF-1 in the epidermis, driven by the bovine keratin 5 promoter (IGF-1 Tg). These mice exhibited premature aging of hair follicles, as evidenced by accelerated hair graying and loss. Single-cell RNA sequencing analyses of dorsal skin highlighted an upsurge in cellular senescence markers and the senescence-associated secretory phenotype (SASP) in hair follicle stem cells (HFSCs), alongside a decline in hair growth and HFSC exhaustion.

Our findings indicate that excessive IGF-1 triggers HFSC senescence, thereby disrupting hair follicle homeostasis. Remarkably, interventions in IGF-1 signaling via downstream mechanisms - specifically blocking acetylated p53 activation via SIRT1 overexpression or senolytic treatment for senescent cell clearance, or reducing IGF-1 through dietary restriction - significantly reduced senescence markers, mitigated premature hair follicle aging phenotypes, and restored the stem cell pool. Our findings provide fundamental insights into the biological processes of hair aging and highlight the therapeutic promise of targeted interventions to rejuvenate aged HFSCs and promote hair follicle health.

5 Likes
#62

This is a helpful review of a complicated study. Without this sort of incisive evaluation, it is hard to appreciate the limits and reasonable conclusions of any particular “scientific finding”.

2 Likes
#63

More data on how low IGF-1 benefits longevity. An open access paper:

Identification of functional rare coding variants in IGF-1 gene in humans with exceptional longevity

Diminished signaling via insulin/insulin-like growth factor-1 (IGF-1) axis is associated with longevity in different model organisms. IGF-1 gene is highly conserved across species, with only few evolutionary changes identified in it. Despite its potential role in regulating lifespan, no coding variants in IGF-1 have been reported in human longevity cohorts to date. This study investigated the whole exome sequencing data from 2,108 individuals in a cohort of Ashkenazi Jewish centenarians, their offspring, and controls without familial longevity to identify functional IGF-1 coding variants. We identified two likely functional coding variants IGF-1 :p.Ile91Leu and IGF-1 :p.Ala118Thr in our longevity cohort. Notably, a centenarian specific novel variant IGF-1:p. Ile91Leu was located at the binding interface of IGF-1–IGF-1R, whereas IGF-1 :p.Ala118Thr was significantly associated with lower circulating levels of IGF-1. We performed extended all-atom molecular dynamics simulations to evaluate the impact of Ile91Leu on stability, binding dynamics and energetics of IGF-1 bound to IGF-1R. The IGF-1 :p.Ile91Leu formed less stable interactions with IGF-1R’s critical binding pocket residues and demonstrated lower binding affinity at the extracellular binding site compared to wild-type IGF-1. Our findings suggest that IGF-1 :p.Ile91Leu and IGF-1 :p.Ala118Thr variants attenuate IGF-1R activity by impairing IGF-1 binding and diminishing the circulatory levels of IGF-1, respectively. Consequently, diminished IGF-1 signaling resulting from these variants may contribute to exceptional longevity in humans.

全文：

https://www.nature.com/articles/s41598-025-94094-y

5 Likes
#64

A new IGF-1 inhibition drug has been approved by the FDA (for use in Acromegaly, where a patient has very high IGF-1 levels due to a tumor, or other defect in the pituitary gland). The price? Only $290,000 per year … @CronosTempi

Crinetics Pharmaceuticals on Thursday said the FDA greenlit its nonpeptide somatostatin receptor type 2 (SST2) agonist Palsonify (paltusotine), making a first-line once-daily oral option available for adults with acromegaly who are refractory to or unsuitable for surgery.

The product, which could offer patients freedom from frequent injections of current therapies, is expected to hit the shelves early next month — with a $290,000 yearly treatment price.

Palsonify’s clearance “marks a new era for those living with acromegaly,” said CEO Scott Struthers, adding that the “approval is the first to come from our deep pipeline of first-in-class, small molecule drugs.”

The FDA decision was supported by two Phase III pivotal trials, PATHFNDR-1 and PATHFNDR-2, which enrolled previously treated and treatment-naïve adults with acromegaly, respectively. In both studies, a significantly higher proportion of participants receiving Palsonify maintained IGF-1 levels ≤1 times the upper limit of normal compared with those on placebo, alongside significant reductions in acromegaly-associated symptoms.

Analysts at HC Wainwright last month said they were fairly confident of an approval, with a label enabling broad use across treatment-naïve patients, those switching from injectables, and those who discontinued therapy. They anticipate “treatment-naïve patients to drive the first wave of adoption post launch, with the other two groups to pick up momentum over time.”

https://firstwordpharma.com/story/6109259

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FINAL-PALSONIFY-FDA-Approval-Call-Slide-Deck.pdf (3.0 MB)

2 Likes
#65

A small early taste of B-LEV? :wink:

1 Like
#66

Well, there are a number of IGF-1 inhibition drugs already on the market, it someone wanted to partake… and most of them are a little lower in price.

I suspect that there could be some moderate benefits to be derived from the use of these by healthy people for disease prevention and perhaps a little lifespan benefit. And perhaps there is some optimal pulsed dosing protocol where you get higher IGF-1 (for healing, growth, etc.) alternated with times of low IGF-1. It would need lots of experiments to find optimal dosing patterns.

From our Friendly GPT5:

Here’s a current snapshot of FDA-approved drugs used to lower IGF-1 in acromegaly (somatostatin receptor ligands, a GH-receptor antagonist, and the two oral options), with typical label dosing and list-price estimates:

Drug (brand) Mechanism Typical maintenance dosing (per FDA label) List price per dose (source) Est. monthly cost Est. yearly cost
Octreotide LAR (Sandostatin LAR Depot) Somatostatin analog ↓ GH → ↓ IGF-1 20 mg IM every 4 weeks (titrate 10–30 mg) (FDA Access Data) ~$4,517 per 20 mg vial (Drugs.com) $4,517 $58,722 (≈13 injections/yr)
Lanreotide depot (Somatuline Depot) Somatostatin analog ↓ GH → ↓ IGF-1 90 mg deep-SC every 4 weeks (range 60–120 mg) (FDA Access Data) ~$4,370 per 90 mg syringe (Drugs.com) $4,370 $56,815 (≈13 injections/yr)
Pasireotide LAR (Signifor LAR) Somatostatin analog (broad receptor) ↓ GH → ↓ IGF-1 40 mg IM every 4 weeks (up-titrate by IGF-1) (FDA Access Data) ~$20,445 per vial (20–60 mg) (Drugs.com) $20,445 $265,779 (≈13 injections/yr)
Pegvisomant (Somavert) GH-receptor antagonist → directly ↓ IGF-1 10–30 mg SC daily (after load; titrate by IGF-1) (FDA Access Data) WAC (30-day supply): 15 mg/day $13,138.55; 20 mg/day $17,516.93 $13,139 (15 mg/day) or $17,517 (20 mg/day) $157,663 (15 mg/day) or $210,203 (20 mg/day)
Octreotide (oral) (Mycapssa) Oral octreotide ↓ GH → ↓ IGF-1 20 mg BID (titrate 20–40 mg BID) (FDA Access Data) ~$3,325 per 28 × 20 mg caps (Drugs.com) → ≈$7,126 per 60 caps/30 days (Drugs.com) $7,126 $85,516
Paltusotine (Palsonify) — NEW (Sep 25, 2025) Oral non-peptide SST2 agonist ↓ GH → ↓ IGF-1 Once-daily tablet; first-line for adults not cured by or not candidates for surgery (per approval PR) (Crinetics) Company-stated WAC ~$290,000/yr (≈$24,167/mo) (STAT)

Notes & caveats

  • Doses above are the commonly used label starting/maintenance doses—clinicians titrate to normalize IGF-1 and control symptoms, so your actual dose (and cost) may differ. Labels: Sandostatin LAR, Somatuline Depot, Signifor LAR, Somavert, Mycapssa. (FDA Access Data)
  • Prices shown are U.S. list prices (WAC or typical cash prices) and don’t reflect insurance, rebates, specialty-pharmacy contracts, or copay programs. (Somavert WAC from Pfizer CT disclosure; others from Drugs.com price guides; Palsonify WAC from company/press reports right after approval).
  • Short-acting octreotide injection is also FDA-approved for acromegaly but is typically used as a bridge/adjunct rather than long-term maintenance; not priced here. (FDA Access Data)

If you’d like, I can tailor this to target doses you’re considering (e.g., lanreotide 120 mg q4w or pegvisomant 25–30 mg/day) and recompute costs, or add payer program links that often reduce out-of-pocket expense.

1 Like
#67

There’s a path to synthesize it for the rest of us, enter the SMILES code:

image
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#68

Another option… buy the dog version of the drug. Loyal for Dogs is using a sister molecule to slow aging in dogs (so people can divert their dog’s prescription to themselves)…

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Source: https://x.com/celinehalioua/status/1972697909440172350

More Reading on Loyal for Dogs:

#69

This isn’t available yet, correct? When will be able to buy this?

#70

Yes - not available yet. In-licenced but in clinical trials right now with Loyal. We’ll see… probably a few years out.

1 Like
#72

That’s the one @RapAdmin posted here right? IGF-1 inhibitors and lifespan extension? - #64 by RapAdmin

#73

Oops! I thought the email I got was the breaking news, didn’t realize the company announced it 2 days ago.

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#74

Definitely not interested since igf1 levels decrease naturally when you get older, and having it too low can rob you of muscles.

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#75

If it decreases the speed of aging sarcopenia should decrease as well as everything else. Is sarcopenia likely if someone does strength training at the same time?

1 Like