Technology blogs

Technology interviews

  • Lex Fridman
    (e.g. with Sam Altman, Demis Hassabis, Yann LeCun, Yoshua Bengio, Geoffrey Hinton, Jürgen Schmidhuber, Andrew Ng, Mark Zuckerberg, Andrej Karpathy, Ilya Sutskever, David Silver, Elon Musk, Vitalik Buterin, Donald Knuth, Guido van Rossum, Bjarne Stoustrup, Leonard Susskind, Frank Wilczek, Lee Smolin, Sean Carroll, Scott Aaronson, Brian Greene, Ray Kurzweil, Max Tegmark, Nick Bostrom, Michio Kaku, Ray Dalio, Daniel Kahneman, David Sinclair, Stephen Wolfram, Magnus Carlsen, Garry Kasparow, …)
  • The Logan Bartlett Show
  • Machine Learning Street Talk
  • Heros of deep learning, Heros of NLP

Learning

Finance

Longevity

(see Ray Kurzweil, David Sinclair, Brad Stanfield)

  • Slow down aging
    (main strategy: avoid cardiovascular disease and cancer, avoid inflammation)
  • Reverse aging (until now just tested in mice and monkeys)
    • Epigenetic reprogramming based on Yamanaka factors
      (➩ startups: Altos Labs, NewLimit, Life Biosciences)
      • Yamanaka factors = 4 genes: Oct4, Sox2, Klf4, c-Myc
      • Proteins coded by these genes induce adult cells to become pluripotent stem cells (iPSCs), i.e. cells that can develop into any specific cell type (Nobel price in medicine 2012 by Shinya Yamanaka).
      • An adult cell is a specialized cell in which certain genes have been turned on or off. This is achieved by adding methyl groups (CH3) to the DNA and/or acetyl groups (COCH3) to the histones around which the DNA is wrapped and depends on the environment of the cell. This same process of DNA methylation that is responsible for cell specialization seems to be also a main contributor to aging.
      • In a way that is not yet completely understood Yamanaka factors restore the methylation pattern of younger cells (which is responsible for which genes are transcribed into proteins).
      • Epigenetic clocks (like the Horvath clock) determine the methylation pattern of a few hundred CpG sites (DNA regions where cytosine is followed by guanine in 5′->3′ direction) and can precisely predict all cause mortality in later life (with a median error of 3.6 years for the Horvath clock). More precise epigenetic clocks than the Horvath clock already exist (with median error of 2.15 years). Recently, also biological clocks derived from retinal imaging have been proposed that seem to be highly associated with expression of the gene ALKAL2.
      • Avoiding the c-Myc gene avoids generating cancer in the de-methylation process. The OSK (Oct4, Sox2, Klf4) genes seem to be safe.
      • Putting OSK genes into an adeno-associated virus (AAV) under the the control of a tetracycline response element (TRE) and injecting the virus into mice allows to activate the OSK genes on demand by giving tetracycline. In this way the reversal of aging can be precisely controlled.
      • The details of how OSK helps in reversing aging are being uncovered more and more: A comparison of quiescent young to quiescent old cells identified 190 genes that were significantly upregulated, and 326 genes that were significantly downregulated. Induction of OSK for four days led to reduced expression in 43.2% of age-upregulated genes and increased expression in 65.3% of age-downregulated genes. Gene ontology (GO) analysis indicated that the top 20 GO biological processes of upregulated genes encompassed key features of aging, including dysregulation of development, localization, and transport, eleven of which were reversed by OSK. The net outcome of this was the demonstration that induction of OSK partially counteracts the aging related changes resulting from senescence [1].
    • Chemical epigenetic age reversal: CiPSC (Chemical iPSC)
      • Key to the identification of small molecules that could reverse aging effects is the design of a high-throughput system that assesses overall cell health and youthfulness in various cell types. It uses a fluorescence-based technique for automated, large-scale cell analysis.
      • Molecules like valproic acid (V), CHIR-99021 (C), E-616452 (6), tranylcypromine (T), forskolin (F), TTNPB (N), Y-27632 (Y), Smoothened Agonist (S), and ABT-869 (A) were evaluated. They were tested in various combinations, some of which also included additives such as sodium butyrate, basic fibroblast growth factor, and alpha ketoglutarate. The results showed that the combination VC6TF was the most effective at restoring a key sign of cellular health. However, this combination didn’t reverse all senescence phenotypes. 6T pre-treatment prevents senescence in human fibroblasts, and 6, T, or 6T extends the lifespan of Caenorhabditis elegans by up to 42.1%. Six specific molecule combinations were selected for further investigation. In these combinations, sodium butyrate was found to be a particularly effective additive. Following treatment with these combinations, the genes affected by the treatment overlapped strongly with genes involved in the switch from cellular rest (quiescence) to senescence. Finally, RNA sequencing revealed that treatment with these molecule combinations resulted in a significant reduction in the cellular transcriptomic age. These treatments reduced the age of cells by more than three years in just four days. They positively correlated with induced pluripotent stem cell populations, suggesting a rejuvenating effect on the cells.