Age1 Venture Capital Launches New Youtube Channel on Longevity & Biotech

20 years ago, scientists figured out how to make mice live 1.5X longer by altering one singular gene. What have we learned since this groundbreaking discovery?

In their debut video, age1 explores the landscape of interventions that slow down aging in mice, with emphasis on the work of the Interventions Testing Program and featuring none other than Dr. Richard Miller himself.

I encourage everyone to click “Subscribe” to this channel, as I’m sure this is just the first of many great videos.

How this tiny mutant mouse lives so, so long (Age1)

Link to video here:


Thanks so much for the feature @RapAdmin! I hope you all enjoy this video as much as I did making it :slight_smile:


I love this video. I was just going to get my pen knife to start working on removing that pesky pituitary gland … when I got the disappointing news from Richard Miller :wink:

A fun and educational video. Well done Alex!


hey thanks! Glad you put the pen knife away i have a feeling you’re pretty dangerous with that thing


Note small typo in your intro post - should be ~1.5x or 50% (not increase by 150%).

Very interesting - most of that seems to be via lowering of IGF-1 and GH:

The extended healthy longevity of mice with single-gene mutations modulating GH/IGF-1 signals is very strong evidence that the aging process per se can be delayed or decelerated in mammals, and that most of the changes that lead to diseases, disabilities, and functional decline in aged animals are under shared control. (Data on caloric restriction, and more recently on drugs that extend mean and maximum lifespan [link], also provide strong support for this viewpoint.) The Miller laboratory contributed to the evidence for delays in age-sensitive functions and diseases in Snell dwarf and GHRKO mice, and also to the observation that cells from these long-lived mutant mice are resistant, in culture, to many forms of injury [link]. These strains include:

(a) Snell dwarf mice, which lack GH, thyroid stimulating hormone, and prolactin, and have approximately 30% - 40% longer lifespan.

(b) GHRKO (growth-hormone receptor knock-out) mice, produced by John Kopchick, which produce GH but cannot respond to it. These mice, too, live up to 40% longer than controls. Mice in which GH is disrupted specifically in fat, muscle, or liver make this an especially good system for dissection of tissue-specific effects.

(c) PAPPA-KO mice (a gift of Cheryl Conover), in which removal of a IGFBP-specific protease is thought to reduce IGF-1 activity in one or more tissues.

Recent publications using these mouse mutants has focused on possible mechanisms by which the alterations in GH and/or IGF-1 signals might promote long-lasting health and slow aging.

● Ozkurede [link] has found alterations in mitochondrial unfolded protein responses.

● Garcia has found alterations in pathways that regulate translation of subsets of mRNAs [link].

● Sadagurski [link] has found lower inflammation in the hypothalamus of these mice.

● Garcia [link] has found augmented cap-independent protein translation of selected mRNAs.

● Endicott [link] has shown increased levels of chaperone-mediated autophagy in these mice.

● Li [link] has found alterations in thermogenesis and inflammation of brown and white fat in these long-lived mice, and shown the role of muscle-specific signals as modulators of fat pathobiology.

● Li [link] has found alterations in brain, muscle, liver, macrophages and fat of Ames dwarf mice, and shown that these are controlled by GH levels in the first few weeks of life.

● Endicott [link] has used a proteomics approach to show which proteins, in liver, are modulated by chaperone-mediated autophagy in long-lived GHRKO mice.

These single-gene mutants provide many opportunities to test ideas about the links between endocrine controls and the timing of late-life decline and survival.


Yes - and there are already drugs that do this (lower IGF-1 and GH) for humans… Another (likely) Longevity Drug - Somavert / Pegvisomant

and… IGF-1 inhibitors and lifespan extension?

Here are the drugs (they are all, sadly, injection drugs - except for one, see below):

Drugs that reduce growth hormone production (somatostatin analogues)

  • Octreotide / Octreotide LAR (Depot) , Sandostatin LAR
  • Lanreotide (Somatuline) Depot
  • Bynfezia (pen), octreotide acetate
  • Signifor LAR (Pasireotide)

Long-acting formulations, including long-acting octreotide, lanreotide, and pasireotide, have been demonstrated to produce consistent GH and IGF-I suppression in patients with acromegaly with once-monthly or biweekly intramuscular depot injections.

Drug to block the action of GH (growth hormone antagonist)

  • pegvisomant (Somavert)

BUT - there is one oral version of Octreotide that came out in 2020 in the US, and 2022 in the EU, that is a pill. This should definitely be studied by the ITP!

Octreotide (Mycapssa) was approved for medical use in the European Union in 2022.[3] As of June 2020, octreotide (Mycapssa) is the first and only oral somatostatin analog (SSA) approved by the FDA.[5] It is on the World Health Organization’s List of Essential Medicines.[6]

Well… there is the small matter of cost. As you can see it is available in tablet form… but the price is a little steep for anyone who’s name isn’t Bryan Johnson (yes, thats $13,000 per month, for 28 tablets):

See the GoodRX data:


Might be good that it also lowers insulin (in a healthy insulin sensitive person) as that seems to be an age accelerator.


For the people more serious about life extension…(and not adverse to injections) we may want to look at trying the injection versions of octreotide. They are available from the Indian pharmacies inexpensively (about $250/month, given a price of around 18,000 rupees and an 83 rupee to the US$ exchange rate)… but the drug needs to be refrigerated which creates an issue for shipment from India to the US. But we don’t know how much the degradation would be… over say a 20 day shipment period. Something to look at… The “Depot” injection only needs to be injected once per month, so pretty low effort (though the daily injections allow you to take breaks on a weekly basis). But perhaps a one month on, one month off, type of schedule would be reasonable and workable.

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In the back of my head I’ve always thought weightlifting and eating high protein will likely decrease lifespan, and possibly healthspan too, but I haven’t researched this properly. It would suck if true, of course.


We still need plenty of muscle mass to avoid dying from sarcopenia.


Sure, but there is an argument low protein and not weightlifting can prevent that too by rejuvenating or slowing the aging process. It would be nice as an older person to be able to maintain muscle mass as easy as a young one. @Olafurpall have mentioned this too.

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Just my observation, but my longevity doc convinced me (69) to go vegetarian. I have done so for 6 months now. My worry was was protein intake in light of all the fussing about protein and sarcopenia. I decided to monitor any effect in the gym as a feedback method.

Nope. I do 2 heavy sessions a week and am achieving pr’s on several muscle groups. I did a dexa scan and am way above average for my age. Apparently there is enough protein in my diet with vegs, beans, about 3 eggs a week, and some cheese.

So my conclusion is I’m getting adequate protein but hopefully not over consuming it (no meat, no powder proteins) and stimulating GH.

I know resistance training increases GH but dont think I’m increasing muscle. I dont look (or weigh) more so I hope the stimulus is only maintaining muscle.

Minimal stimulus of GH as we age seems like a doable strategy.


Heavy agree - this is an area of strong interest for me. I’m not really convinced that modulating circulating levels of GH in either direction would be useful for longevity.

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would stray away from using an IGF inhibitor

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I am surprised you are not positive on GH/IGF1 modulation for longevity, I think it probably one of the best researched pathways. And your company is an investor in Loyal for Dogs which has announced (or at least Celine confirmed to me in a conversation at the Longevity Summit) that their first drug targets the IGF1 pathway.

Have you reviewed this data? IGF-1 inhibitors and lifespan extension? - #6 by RapAdmin

The authors note:

In summary, reducing the activity of the GH/IGF-I somatotrophic axis is perhaps the most validated and consistent genetic intervention to extend mouse lifespan and healthspan. In addition GHR/IGF-I deficiency is also among the few phenotypes that is well characterized in humans (patients with Laron syndrome) with very few side effects in adults, even considering the extreme level of GH receptor deficiency and the resulting >80% reduction in circulating IGF-I.

Obviously, we’d be doing it after we are fully grown, so we wouldn’t look like the Laron Syndrome people :slight_smile:

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Why would you avoid using an IGF inhibitor?

One thing I find interesting, and that potential may minimize or eliminate the benefits of later life reductions of GH/IGF1 as a life extension strategy, is that the lifespan benefits of low growth hormone / IGF1 levels are significantly reduced in these long-lived strains of mice if they are given a few weeks of GH injections to normalize their GH/IGF1 levels during that short period.

In this study, done by Richard Miller’s team, they found that only a few weeks of GH injections reversed many aspects of the longevity phenotype. I’m not sure if there have been any studies yet on low-GH / IGF1 levels implemented later in life.

The exceptional longevity of Ames dwarf (DF) mice can be abrogated by a brief course of growth hormone (GH) injections started at 2 weeks of age. This transient GH exposure also prevents the increase in cellular stress resistance and decline in hypothalamic inflammation characteristic of DF mice. Here, we show that transient early-life GH treatment leads to permanent alteration of pertinent changes in adipocytes, fat-associated macrophages, liver, muscle, and brain that are seen in DF mice.

Thus, many of the traits seen in long-lived mutant mice, pertinent to age-related changes in inflammation, neurogenesis, and metabolic control, are permanently set by early-life GH levels.

source: Transient early life growth hormone exposure permanently alters brain, muscle, liver, macrophage, and adipocyte status in long-lived Ames dwarf mice - PubMed

In other words, these Ames dwarf mice in this study had low GH/IGF1 levels their entire life, except for this brief period of a few weeks when the injected higher levels of GH/IGF1, and the result was that many of the benefits of low GH/IGF1 were eliminated. The question that then comes up is if we as humans have mostly higher GH/IGF1 until age (pick a number, 30, 40, 50 years), and then we lower it, will we see any benefits that are seen in the Ames dwarf mice from lifelong low GH/IGF1.

So - there is the question in my mind as to whether later life GH/IGF1 restriction will accomplish significant longevity benefits. But I’ve not searched all the literature on this issue. Perhaps someone else has some knowledge in this area.

At the same time, it doesn’t seem like there is much risk with lower IGF1 or GH, given the normal lifespans of Laron syndrome people.


It’s so strange to see the OG longevity people screaming about IGF-1 being… accidentally right. And about CR too… and about cholesterol… and about…

Okay they might be better than what was expected.

? what are “OG Longevity people”?

It’s slang:

: someone or something that is an original or originator and especially one that is highly respected or regarded

I am not a formal boi.

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