#8

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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#9

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.

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#10

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

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#11

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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#12

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.

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#13

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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#14

would stray away from using an IGF inhibitor

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#15

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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The science behind lifespan extension: Metabolic dysfunction (Loyal for Dogs)
#16

Why would you avoid using an IGF inhibitor?

#17

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.

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The lifespan extension effect by GHR-KO doesn't translate to humans
#18

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.

#19

? what are “OG Longevity people”?

#20

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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#21

Can you translate above - I don’t understand what you are trying to say

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#22

Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice - PubMed Selenium supplementation will lower IGF-1 to mimicking methionine restriction diet.

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#23

Thanks (yeah, we just want to over do it, but I eat a couple of Brazil nuts).

#24

I was not putting a lot of faith in the theories from certain type of longevity enthusiasts. They are being proven right, possibly with IGF-1, but most assuredly with lipids. So they were better than I was expecting them to be.

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#25

FWIW this is not me speaking on behalf of age1 - and I do think Loyal’s thesis of inhibiting IGF in unusually large dog breeds is sound.

The rationale I’ve seen for inhibiting growth hormone in adulthood has been sparse; there was this paper that showed mild positive lifespan effect for female mice starting with GH inhibition at 6mo, but that would not compel me to start taking a drug that has a similar mechanism of action.

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The lifespan extension effect by GHR-KO doesn't translate to humans
#26

Thanks Alex. Seems like the downside risks are quite low… I’ve yet to see any negative reports on lower GH/IGF1 levels. I could imagine trying this on a pulsed basis just to see the effects on bloodwork, etc. given the low price of octreotide.

Growth hormone receptor gene disruption in mature‐adult mice improves male insulin sensitivity and extends female lifespan

We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature‐adult mice at 6 months old (6mGHRKO). These mice exhibited GH resistance (reduced IGF‐1 and elevated GH serum levels), increased body adiposity, reduced lean mass, and minimal effects on body length. Importantly, 6mGHRKO males have enhanced insulin sensitivity and reduced neoplasms while females exhibited increased median and maximal lifespan. Furthermore, fasting glucose and oxidative damage was reduced in females compared to males irrespective of Ghr deletion. Overall, disrupted GH action in adult mice resulted in sexual dimorphic effects suggesting that GH reduction at older ages may have gerotherapeutic effects.

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#27