jmachado.eth

YPO Portugal & OPM HBS alumni // A mind is stuck in the intersection of AI, $BTC, Sustainable Textiles & rapamycin // Please don’t follow me

[MEME THE LEFT @memetheleft]

The same people who cheered for John Wick killing dozens of people to avenge his dog are super mad about a vigilante killing Muslim rapists.

[Agustín Romo @agustinromm]

Tremenda escena de la nueva película "Citizen Vigilante" que trata sobre la invasión musulmana que está sufriendo Europa y por la cual hay millones de violaciones a mujeres europeas. La película trata de un justiciero anónimo que va vengando las víctimas y fue prohibida en Alemania, pero Elon Musk la subió entera a X para que todos la puedan ver.

[Code-Reinho-Tactical @CodeReinhoTac]

Vous cachez une climatisation sous votre plancher n'est ce pas ?

[Abdulkadir | Cybersecurity @cyber_razz]

“A man who has not hit his Claude limit by noon has wasted his morning.”

-Socrates

[jmachado.eth @Jmachadopt]

@EU_Commission please stop wasting taxpayer money

[jmachado.eth @Jmachadopt]

💪🏼

[Capitán Bitcoin @CapitanBitcoin]

🚨Mexicana desesperada en España. Se hizo autónoma. Se siente superada cada trimestre solo pagando IVA + contribuciones. Quiere cerrar el negocio:

“España NO ES para emprendedores”, asegura.

[Matt Kaeberlein @mkaeberlein]

Wanna know what I am so tired of?

I am so tired of armchair science commentators and influencers posting uninformed and misleading comments about longevity science.

I understand the knee-jerk reaction, because there are plenty of irresponsible and sometimes dishonest people promoting sirtuin activators (or fake sirtuin activators such as resveratrol) as proven longevity therapies. Rapamycin less so, although the hype can definitely get ahead of the data at times.

As someone who has been working in this space on both sirtuins and rapamycin for nearly 30 years - in fact I co-authored both the first sirtuin longevity paper and the first rapamycin longevity paper - I know something about this topic. Rapamycin is definitely not a "dead end". In fact, it's about as far from a scientific dead end as you can possibly get at this point. Sirtuins are harder to quantify, but it seems premature to characterize the entire family of proteins as a "dead end" for longevity at this point.

Sirtuins have many important biological functions; that's clear. They do not appear to be central regulators of longevity in mammals, but they do intersect with the longevity network in interesting ways. SIRT6 might indeed be a legitimate target for slowing aspects of biological aging, although the body of literature here is limited and comes from only a few labs. However, the fact that there is both mouse data and human genetic data for SIRT6, suggests perhaps we should not completely ignore this protein as a potential target for longevity. In my opinion, it is extremely unfortunate that people have started selling putative "SIRT6 activator" supplements, but that follows the long tradition in the sirtuin space of letting marketing get way out in front of legitimate science.

Rapamycin, on the other hand, is by far the most robust and reproducible drug for increasing lifespan and slowing age-related decline in laboratory organisms spanning more than one billion years of evolution. This is backed up by multiple genetic lines of evidence using loss of function and gain of function variants in the mTOR pathway, and has been replicated by dozens of labs across hundreds of studies. It is about as rock-solid as things ever get in biology.

There is also unpublished (but presented at conferences) data that rapamycin can increase lifespan in non-human primates.

What about mTOR and rapamycin in the real world? There is human genetic data also supporting the idea that mTOR signaling is associated with longevity in people. There is early randomized clinical trial data in companion dogs suggesting that rapamycin can improve age-related declines in heart function, activity, and quality of life. There is a growing body of data across numerous independent studies that rapamycin may improve immune aging, brain aging, ovarian aging, age-related changes in body composition, and a variety of chronic inflammatory conditions in humans. It's true that most, but not all, of these studies are small and underpowered for strong conclusions. Fortunately, a couple of major initiatives, including the ARPA-H PROSPR and the R. Ken Coit-funded clinical trial at U. Arizona, will generate larger clinical trial data sets for rapamycin in older adults in the coming years.

This information is all in the published literature for anyone who wants to put in the effort to become informed. I'll also be speaking on this topic at @LongevityDublin next week. The title of my talk is "Is Rapamycin Dead?". You can probably guess the answer. Once I get back, I will put together a video for @longevityscipod . You might want to check it out.

[jmachado.eth @Jmachadopt]

@Adityalch @reallyoptimized your confidence level given the scale of your ignorance is uncanny. must be great to live life like that

[jmachado.eth @Jmachadopt]

@Adityalch @reallyoptimized Im on weekly rapamycin and I have no inhibition of muscle growth whatsoever. without a dexa it's not possible to compare but I would put my money on my body composition being better with than without rapamycin

[alon @alonzuman]

having a wife is crazy cuz its like claude code but it prompts you instead

[World of Engineering @engineers_feed]

Voyager 1 is 24 billion kilometers from Earth.

It communicates with us using a 23-watt transmitter.
Less than a refrigerator light bulb.

The signal takes 22 hours to reach us, traveling at the speed of light.

By the time it arrives, it's 20 billion times weaker than the power of a digital watch battery.

NASA's Deep Space Network picks it up using 70-meter dish antennas cooled to near absolute zero to reduce electronic noise.

The engineering required to hear a 23-watt signal from 24 billion km away is arguably more impressive than the spacecraft itself.

Launched 1977.
Still transmitting.
Still being heard.

We built something that works perfectly, 47 years later, in conditions no one has ever tested in.

That's what engineering for the long term looks like.

[jmachado.eth @Jmachadopt]

🚀

[Don Keith @RealDonKeith]

🚨EU plans VPN crackdown: New age ID system “cannot be bypassed” via VPNs.

Couldn’t stop illegal migration, but suddenly goes full North Korea on controlling what Europeans read online.

[𝐆𝐫𝐢𝐦𝐚𝐥𝐝𝐮𝐬 @ImperiumFirst]

3/21: “Iran has 48 hours to make a deal!”
3/23: “Iran has 5 days to make a deal!”
3/26: “Iran has 10 days to make a deal!”
4/7: “Iran has 2 weeks to make a deal!”
4/21: “Iran has until Sunday to make a deal!”
4/25: “…uh they’ll call us at some point”

[Visegrád 24 @visegrad24]

The Kuban Agrarian University in Russia decided to invite a Russian soldier fighting in Ukraine to speak online to a room full of their students to encourage them to sign up with the Russian Army

Instead, a Ukrainian soldier appeared on the screen

[Collin Rugg @CollinRugg]

NEW: Astronaut Reid Wiseman shares a video of ‘Earthset’ that was taken with his iPhone

“This is uncropped, uncut with 8x zoom which is quite comparable to the view of the human eye…” Wiseman said.

This has to be the greatest iPhone video of all time.

[jmachado.eth @Jmachadopt]

🚀🚀🚀

[Raúl Torres🇪🇸 @RaulTorresPLD]

Este vídeo es alucinante: compara los tiempos de despeje de plataforma de lanzamiento de #SLS-Artemis y #Saturno5-Apolo. La contribución de los SRBs claramente marca la diferencia, pero yo sigo enamorado del #Saturno5.

[jmachado.eth @Jmachadopt]

@BradStanfieldMD thanks for the work @BradStanfieldMD 👍🏼

[Aakash Gupta @aakashgupta]

Christopher Nolan just showed Trojan Horse footage from The Odyssey at CinemaCon. The business math behind this movie is wild.

$250 million budget. His most expensive film ever. First movie shot entirely on IMAX 70mm cameras. No franchise, no sequel, no superhero IP. The source material is a 3,000-year-old poem.

IMAX opening weekend tickets went on sale a full year before release. They sold out in 12 hours. $1.5 million in ticket revenue before a single TV spot aired.

The trailer pulled 121.4 million views in 24 hours. More than Universal's Wicked sequel. More than double what Oppenheimer's first trailer did in the same window.

Today's footage confirmed Charlize Theron is playing Calypso, the nymph who kept Odysseus trapped on her island for seven years. The scene opens with Damon asking her "How long have I been here?" He can't remember if he had a wife or a son.

That's pure Nolan. Starting the story in captivity, with a man who's lost his own identity. The same filmmaker who opened Memento backwards.

The cast is absurd: Damon, Holland, Hathaway, Pattinson, Zendaya as Athena, Lupita Nyong'o, Theron, Bernthal as Menelaus, Safdie as Agamemnon, Mia Goth, Leguizamo, Elliot Page, Travis Scott. Nolan joked it would be faster to list who isn't in it.

His last five films averaged $680 million worldwide. Oppenheimer made $976 million with an R rating and a three-hour runtime about a physicist.

Every studio spent the last decade convinced original films can't open big. Nolan's response: adapt the oldest story in Western literature. Homer's been in public domain for about 2,500 years.

Nolan IS the franchise. His name on a poster does what a superhero logo used to do. Universal figured this out when they signed him after Warner Bros let him walk over a streaming window dispute. Twenty years of partnership, gone.

July 17. IMDb's most anticipated film of 2026. Built from a poem your ninth-grade English teacher assigned.