#1

IF what he is saying in this interview is true, this is a ground braking discovery and a world record for a longevity intervention. Even if exactly this compound doesn’t work in humans the fact that this mechanism of T cell rejuvenation exists makes me super optimist for our future:

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Disruptors of the Sestrin AMPK/MAPK Complexes
#2

I believe this is the Nature article referenced in the interview:

and this article is a synopsis of that work:

from the video (with slight edits for clarity) at 0:26:

[the transfers of telomeres] rejuvenate each single senescent cell in your body and this is responsible for extension of the lifespan in the animals that we are treating with DOS compound. We’re treating with this rivers [?] of telomeres from 2.5 up to five years in the in the black six Mouse model, which is amazing. So we believe that this is the key which is responsible for maintaining healthspan and lifespan.

DOS (Disruptors of sestrin-MAPK interactions) is a compound that rejuvenates T cells by disrupting sestrin-MAPK complexes (sMACs), which leads to telomere elongation in T cells.

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#3

He also says (at 19:45) that the rejuvenated T-cells are reprogrammed in the thymus to be much more immuno-tolerogenic. This potentially has huge implications for autoimmune diseases.

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#4

Mice in labs live in pretty sterile environments, this is probably a main reason why mildly immunosuppressive interventions can work so well on extending longevity by reducing inflammatory process.
When you start messing with T-cell in actual humans and then they get exposure to EBV, CMV, HPV, Parvovirus, COVID, etc. it may not end well.

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#5

In the interview he said this intervention helps fight infections much better than actual technology. He claims HIV, senescence, vaccines and even some cancers could be a thing of the past thanks to this platform.

Also what is even wilder is that mice get a life extension of 2.5 even 5 years. Mice usually live 3 years, we are talking about doubling the lifespan!

All of these are wild claims and they may be all false or exagerations. Only time will tell.

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#6

It seems too good to be true. He provides some plausible metabolic explanations, quotes a pre-print, and references unpublished data. He also seems optimistic that the small molecule will solve the problems of susceptibility to a number of diseases (including HIV!), senescence, telomere shortening, and aging itself. It might be world-changing, but I’ll wait for reproducible results.

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#7

Second interview of Dr Alessio Lanna where he explains what is the mechanism behind the life extension you get when you rejuvenate a T cell. Also he thinks this is the mechanism behind the life extension obtained using parabiosis.

If true, this guy needs investment as big as Altos Lab.

1 Like
#8

An AI Summary of the videos by this guy:

视频 #1: Rejuvenating the Immune System to Extend Lifespan & Healthspan | Dr Alessio Lanna Interview

Telomere Transfer and Lifespan Extension

  • Recent research indicates that rejuvenated T cells can undergo a telomere transfer reaction, allowing them to disseminate telomeres throughout the bloodstream.
  • These telomeres travel to various parts of the body, including the brain and gut, rejuvenating senescent cells and contributing to lifespan extension in treated animals.
  • In studies with the black six mouse model, the lifespan extension observed ranged from 2.5 to 5 years, showcasing the potential of telomere transfer in enhancing healthspan and lifespan.
  • The technology aims to rejuvenate CD4 T cells, which could significantly improve both lifespan and healthspan in humans.

Overview of Sentcell and Immune Senescence

  • Dr. Lanna, founder and CEO of Sentcell, focuses on developing therapies that address immune senescence, particularly in T cells.
  • Immune senescence refers to the deterioration of immune function as cells age, leading to issues such as reduced vaccination responses and increased cancer susceptibility.
  • Sentcell aims to modulate T cell senescence, as current treatments do not effectively rejuvenate these immune cells.
  • The company’s research emphasizes the importance of rejuvenating CD4 T cells to enhance overall organism health and longevity.

Mechanism of T Cell Aging

  • Traditionally, it was believed that T cells age through repeated divisions after encountering antigens, leading to telomere shortening.
  • Recent findings suggest that the aging fate of T cells is determined before their first division, based on whether they receive telomere donations from antigen-presenting cells (APCs).
  • If T cells receive telomere donations, they can avoid senescence and maintain stem-like characteristics, whereas those that do not will eventually senesce.
  • This novel understanding shifts the focus from telomerase activity to the significance of telomere transfer in T cell longevity.

Role of Telomerase and Ultra Short Telomeres

  • Telomerase is known for extending telomeres, but its role in rejuvenation may not be as significant as previously thought, particularly concerning ultra short telomeres.
  • Ultra short telomeres can trigger senescence, and telomerase is ineffective at elongating them once they fall below a critical length.
  • Telomere transfer from APCs can eliminate ultra short telomeres before T cells divide, preventing the onset of senescence.
  • The discovery of telomere transfer as a mechanism to rejuvenate T cells offers new insights into combating age-related immune decline.

Rejuvenation of Senescent T Cells

  • The rejuvenation process involves not only preventing T cells from becoming senescent but also restoring function to those already in a senescent state.
  • Research indicates that rejuvenated T cells can learn new functions, including reprogramming their T cell receptor (TCR) specificity.
  • This reprogramming allows T cells to respond to specific antigens, such as those from vaccines, enhancing their effectiveness.
  • The rejuvenation of T cells can also lead to thymus regrowth, which typically involutes with age, thereby improving the overall immune response.

Clinical Implications and Trials

  • Preclinical trials show that the rejuvenating compound can significantly enhance immune responses in older animals, particularly in response to vaccinations.
  • The upcoming clinical trial at University College London aims to evaluate the effectiveness of the rejuvenating compound in restoring immune function in elderly populations.
  • Initial findings suggest that the rejuvenating compound can restore immune protection to levels comparable to those seen in younger individuals.
  • Future studies will explore the potential of the compound to provide immunity against various infections, even without vaccination.

Broader Applications of the Technology

  • Sentcell’s research extends beyond T cell rejuvenation, exploring potential applications in anti-cancer and anti-neurodegenerative therapies.
  • The technology could also be utilized to target and eliminate the HIV provirus from infected T cells, providing a potential cure for HIV.
  • The flexibility of the rejuvenating compound may allow for broader applications in treating various age-related diseases and improving overall immune health.
  • As research progresses, the potential for the compound to benefit younger populations with senescent T cells is also being considered.

视频 #2 - This Therapy May Cure AIDS And Extend Your Lifespan | Dr Alessio Lanna

Current Status of HIV Treatment

  • Currently, there is no definitive cure for HIV, but researchers are exploring innovative approaches to treatment.
  • One strategy focuses on individuals known as elite controllers, who can manage HIV replication without antiretroviral therapy (ART).
  • Researchers are investigating whether it is possible to evoke a similar elite control state in non-elite individuals.
  • Pharmacological methods have been developed that can trigger pathways similar to those utilized by elite controllers to suppress HIV replication.
  • Studies have shown that these methods can lead to the degradation of proviral DNA in treated patients.

Understanding HIV Infection

  • HIV is classified as a retrovirus, specifically a lentivirus, with a single-stranded RNA genome that is reverse transcribed into DNA.
  • The DNA is integrated into the genomes of host cells, primarily CD4 T-cells, establishing a reservoir for the virus.
  • The replication of HIV leads to the gradual depletion of CD4 T-cells, resulting in immune deficiency and potential progression to AIDS.
  • Although ART can suppress viral replication, it does not eliminate the virus, necessitating lifelong treatment.
  • Current treatments can be burdensome due to the associated stigma and chronic inflammation, highlighting the need for more effective solutions.

Challenges in Eradicating HIV

  • Eradicating HIV is challenging due to the presence of a viral reservoir in long-lived CD4 T-cells, which can reactivate upon cessation of ART.
  • Efforts to eliminate this reservoir include strategies that aim to “shock and kill” the virus or utilize CRISPR technology to target HIV DNA.
  • Attempts to modify chromatin landscapes to evoke HIV from reservoirs have been explored, but challenges remain in effectively targeting the virus.
  • Successful cases of HIV eradication through bone marrow transplants have been documented, but this approach is not feasible for the broader population.

Innovative Approaches to HIV Treatment

  • A new approach focuses on pharmacologically triggering pathways that can lead to the degradation of proviral DNA in CD4 T-cells.
  • This treatment has shown promise in preclinical models, suggesting a potential path toward a functional cure for HIV.
  • The aim is to achieve a state where individuals can maintain an undetectable viral load without ongoing ART.
  • Mathematical modeling indicates that the likelihood of proviral reactivation could be extremely low after treatment.
  • This innovative method may lead to significant advancements in the management of HIV, potentially allowing for long-term remission without daily medication.

Mechanism of Action of New Treatments

  • The treatment involves using a specific pharmacological agent that modifies the DNA of the virus within infected T-cells.
  • This agent triggers a rejuvenation response in CD4 T-cells, allowing them to outcompete the HIV integrase protein, which is essential for viral replication.
  • By displacing the integrase from the chromatin, the treatment enables the degradation of proviral DNA from the host genome.
  • This process does not damage the T-cells, allowing them to recover and potentially switch to a stem-like state.
  • The rejuvenated T-cells can clear HIV from their genomes, leading to a negative HIV status in treated individuals.

Clinical Trials and Future Directions

  • Clinical trials are planned to begin in 2026, with a focus on both safety and efficacy of the new treatment in HIV-infected individuals.
  • The trials will involve dose escalation to determine the optimal treatment regimen.
  • The research aims to demonstrate that the treatment can effectively eliminate HIV from the genome of CD4 T-cells.
  • There are hopes that this innovative approach may also extend beyond HIV to other viral infections that integrate into host genomes.
  • The ultimate goal is to provide a viable alternative to lifelong ART, allowing individuals to live without the burden of daily medication.

Rejuvenation and Immune System Function

  • Recent studies indicate that rejuvenation of T-cells can enhance immune function and potentially reverse the effects of aging.
  • The rejuvenated T-cells can release factors that improve the health and longevity of other cells in the body.
  • This process involves the transfer of telomeric factors from T-cells to other cells, promoting overall rejuvenation.
  • The research suggests that CD4 T-cells play a critical role in maintaining immune health over time.
  • Innovative applications of this research could lead to new therapies that enhance immune responses against various pathogens.
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#9

This seems like a really big deal and clinical trials are imminent. Only a couple of comments under the Modern Healthspan video. Not all that much here, either. Is overpromising fatigue setting in? What am I missing?

#10

Let’s see the peer-reviewed lifespan studies.

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#11

Peer review may not be needed. What’s different here is that (assuming his projected 2026 timeframe for clinical trials is accurate) FDA approval for an HIV therapy could come quickly. Once approved for that, it could be prescribed off-label for longevity.

This could be fast-tracked, while other promising longevity interventions would have a much longer path to the clinic. I want a pill that will make my fur dark and glossy as soon as possible.

He invites emails and says he answers every one he gets.

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