#1

Dr. Kaeberlein makes a good point. It seems like the field has become myopic on what has already been discovered which is preventing new discoveries which may be even better than what we already have.

I think the Ora Biomedical million molecule challenge could break this paradigm, but it seems no one is taking up the ball to run with it when a new longevity lead has been generated.

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#2

There are always difficulties with the process of deciding what available funds either from general governmental (tax) resources or private/charitable funding are placed into which research.

It is possible to make faster progress through biohacking, but only if people are rigorous about the testing. After all the safety testing for most substances has been done with a number of parameters.

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#3

He makes some good points although I donā€™t completely agree. Do I feel like I havenā€™t seen much ā€œnewā€ in the last year? Yes, but not because there isnā€™t new stuff out there. Thereā€™s plenty. It just isnā€™t new to me or it requires really getting into the weeds to see the new stuff.

I also donā€™t agree with his pursuit of a better Rapamycin. Itā€™s fine to do, but I donā€™t think that is where the answer is. Searching for a single compound fountain of youth is unlikely to be successful. Rapamycin is not going to make us all live to 125 or 150. Itā€™s going to be a complex multifaceted intervention.

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#4

I agree that itā€™s likely to be a complex intervention, but a better Rapa might just be a part of one. Individual compound screening is just the ā€œfirst stepā€ in Oraā€™s process. The idea is to screen a lot of single compounds first and afterwards their combinations. But people can (and already have) picked a combination of compounds for screening.

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#5

And that is the crux of the matter. There will be no one and done solution.

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#6

Aging: Caused by sMAC Signaling Disruptions, Resolved by DOS

Aging underlies a gradual loss of physical and mental function and is now recognized as the primary driver behind 85% of age-related diseases. This feedforward signaling cascade begins with stress, driving the formation of an immunological blockade; the Sestrin MAPK Activation Complex (sMAC), which triggers cellular senescence and the release of pro-inflammatory signals known as the senescence-associated secretory phenotype (SASP). As inflammation increases, immune function is disrupted, creating an environment that fosters the emergence of age-related diseases. In turn, the resulting diseases create a feedback loop that exacerbates stress, inflammation, and immune compromise, further accelerating the aging process and leaving the body vulnerable to lethal opportunistic infections. This pathway is highly conserved from plants to mammals.

What you have just read is the identification of sMAC as the fundamental, evolutionarily conserved mechanism triggering a Feedforward/Feedback loop that drives the aging process.

Disruptors of Sestrin-MAPK immune-inhibitory complexes (DOS) represent a revolutionary intervention, directly restoring appropriate signaling through the sMAC molecular pathway and resolving its inhibitory hold on immune resilience. DOS compounds effectively halt the cascade of senescence and SASP-driven inflammation caused by the sestrin-MAPK complex. This restores T-cell fitness, rejuvenates the adaptive immune repertoire through de novo T-cell receptor (TCR) rearrangements, and promotes stem-like T cells with prolonged immunological memory. Remarkably, DOS-mediated rejuvenation reprograms immune cells to combat both existing and novel challenges without vaccination, mitigating systemic inflammation and reversing the pro-aging feedback loops. This intervention not only addresses immune suppression but propagates vitality across systems, heralding a new era of extended disease-free healthspan and longevity.

DOSā€™s targeted resolution of sMAC-driven immune dysfunction is the mechanistic key to resolving aging.

DOS treated T cells regain robust functionality and establish an immune environment conducive to systemic rejuvenation. A critical aspect occurs when the DOS treated, reinvigorated T cells interface with antigen presenting cells (APCs). This interaction triggers an exosome-mediated transfer of telomeres from APCs to the T cells. Exosomes are small, membrane-released vesicles that transport biomolecules like signaling molecules and genetic material between cells. The rejuvenated T cells then undergo asymmetric division, with one daughter cell receiving the majority of these telomere-rich exosomes. This specialized daughter cell, now equipped with elongated telomeres, releases them systemically as extracellular vesicles targeting senescent cells across organs, restoring chromosomal stability, rebalancing tissue homeostasis, and mitigating chronic inflammation. This orchestrated process bridges localized immune rejuvenation with systemic anti-aging effects, providing a comprehensive approach to extending healthspan and vitality.

Collectively these DOS initiated processes define the ultimate medical breakthrough - safe, effective and readily achievable age reversal.

DOS has not demonstrated any off-target side effects or toxicities, even when administered at 600 times the therapeutic dose of 0.05 mgs per kg.

The mechanism responsible for TCR rearrangements also eliminates integrated proviral scripts from the genome, providing a sterilizing cure for viruses like HIV. References and Additional Informational Resources:

[1] [2024] Rejuvenation driven reprogramming in T lymphocytes.pdf

[2] [2024] Disruptors of sestrin-MAPK interactions rejuvenate T cells and expand TCR specificityl.pdf

[3] [2022] An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory.pdf

[4] [2017] A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging.pdf

[5] Disruptors of the Sestrin AMPK/MAPK Complexes: Overview

[6] Podcast Interview of Professor Alessio Lanna, Ph.D.

[7] sMAC/DOS Overview: Age-Regression-sMAC/DOS

[8] A complete molecular mechanistic overview of sMAC/DOS technology is available in a slide deck format.

This non-confidential overview was prepared by Michael Slattery for SenTcell and Professor Allesio Lanna, Ph.D. Detailed Non-confidential overview: Age-Regression.Com/DOS-sMAC and SenTcell.

Michael Slattery

BioLogic ARC Email Michael@Age-Regression.com Phone: (760) 272-5845

Last revision: 01/21/2025

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