Bilu Huang

🧬 Conquer Aging via TRCS
Independent Theoretical Researcher
TRCS Originator | First-Principles Thinker
Aging Biology | Climate | Fusion | @BiluHuangAging

[Bilu Huang @BiluHuang]

After 30 years of thinking about aging, I proposed a theoretical framework:

TRCS (Telomere DNA and Ribosomal DNA Co-regulation Model for Cell Senescence)

Aging is not random damage —
but a programmed process at the DNA level.

This is the starting point.

More to come.

[Bilu Huang @BiluHuang]

https://t.co/jKlxHEzVJt

[Bilu Huang @BiluHuang]

Excited to see Professor Alessio Lanna @lanna_alessio moving into First in Human immune rejuvenation via telomere river therapy!

https://t.co/dhgHgOodUY

[Bilu Huang @BiluHuang]

A single dose of JV101 (AAV9-modTERT) reduced the DNA damage response (DDR), p53 activation, inflammation, and ROS levels. Consistent with the predictions of TRCS model, thank you very much. 👏

[Bilu Huang @BiluHuang]

A noteworthy development from China:

Nanjing-based Juvensis Therapeutics has announced that its telomerase gene therapy candidate, JV101, has received FDA IND clearance for the treatment of heart failure.

According to the company, a single intracoronary administration is designed to achieve long-term therapeutic gene expression, with efficacy reportedly sustained for more than 12 months in multiple preclinical heart failure models.

The IND application was supported by first-in-human clinical data presented at ASGCT 2026, where no dose-limiting toxicities or treatment-related serious adverse events were reported. Improvements in left ventricular ejection fraction (LVEF), reductions in left ventricular end-diastolic volume (LVEDV), and improvements in exercise capacity and quality of life were also reported. More than 50% of participants demonstrated improvements in exercise capacity and quality-of-life measures.

In addition, the company reported positive results across seven preclinical studies spanning multiple heart failure indications, including pressure-overload heart failure, post-myocardial infarction heart failure, diabetic cardiomyopathy, hypertrophic cardiomyopathy, and heart failure with preserved ejection fraction (HFpEF).

For those interested in aging biology, this development is noteworthy for another reason.

One of the central predictions of the TRCS (Telomere DNA and Ribosomal DNA Co-regulation) framework is that telomere maintenance is not merely a biomarker of aging, but is a cause in age-related degenerative decline. If so, interventions targeting telomere biology could potentially produce meaningful therapeutic benefits in degenerative diseases.

Of course, FDA IND clearance is not proof of efficacy, and clinical outcomes remain to be established through rigorous trials. Nevertheless, JV101 represents one of the most significant clinical tests to date of a telomere-targeted therapeutic strategy in a major age-related disease.

I will be following the progress of this program with great interest.

[Bilu Huang @BiluHuang]

Company website:
https://t.co/sjciTWOK9V

Original company announcement (Chinese):
https://t.co/a8i1oyj3E1

[Bilu Huang @BiluHuang]

@irat1onal @strygah Spot on, Ira! Welcome to read my proposed hypothesis on the novel pathological mechanism of degenerative cardiovascular and cerebrovascular diseases.https://t.co/E2yerjgZ99

[Bilu Huang @BiluHuang]

@irat1onal @strygah Spot on, Ira! Welcome to read my proposed hypothesis on the novel pathological mechanism of degenerative cardiovascular and cerebrovascular diseases.https://t.co/E2yerjgZ99

[Bilu Huang @BiluHuang]

https://t.co/5a3boeMByp

[Bilu Huang @BiluHuang]

iPSCs are essentially equivalent to ESCs, capable of unlimited proliferation and differentiation into all cell types. The problem is that differentiated cells derived from either PSCs or ESCs will be eliminated by the immune system, making them impractical for regenerative therapy.

[Bilu Huang @BiluHuang]

iPSCs are essentially equivalent to ESCs, capable of unlimited proliferation and differentiation into all cell types. The problem is that differentiated cells derived from either PSCs or ESCs will be eliminated by the immune system, making them impractical for regenerative therapy.

[Bilu Huang @BiluHuang]

@Woodchipper9000 @acommanman766 @YouTube This hypothesis that "If multiple doses are administered periodically, the effect may be amplified" is not supported by evidence.

[Bilu Huang @BiluHuang]

Telomeres and the Future of Dementia Care with Dr. Michael Fossel https://t.co/SunUqsuZLl via @YouTube

[Bilu Huang @BiluHuang]

@Woodchipper9000 @acommanman766 @YouTube https://t.co/nVtLYZOf3k

[𝗚𝗥𝗘𝗘𝗞 𝗦𝗔𝗚𝗘 ⚕️ @greek_scientist]

🚨 The moment a supposed scientist like @davidasinclair brags about “109% lifespan extension” in old mice instead of saying “about 7% longer total lifespan,” my SCAM ALARM goes off. 🚨

And it won’t work in young mice.

That's marketing dressed up as science for profit.💲
#aging

[Bilu Huang @BiluHuang]

@Woodchipper9000 @acommanman766 @YouTube https://t.co/JOeCSJcJHA

[Bilu Huang @BiluHuang]

https://t.co/LKdpSMiFzk

[Santa Fe Institute @sfiscience]

Reserve your free tickets for SFI’s Community Lecture with Thalia Wheatley on June 23, 7:30 pm at the Lensic Performing Arts Center.

For more than a century, neuroscience has viewed intelligence as a property of individual brains. But brains did not evolve in isolation. Humans are an intensely social species whose minds are continuously shaped by other minds. Increasingly, evidence suggests that our most sophisticated cognitive abilities emerge not from solitary brains, but from networks of interacting people.

In this lecture, Wheatley will explore conversation as a powerful mechanism for coupling minds — aligning attention, beliefs, emotions, and behavior across individuals. Drawing on research from neuroscience, psychology, and network science, she will show how everyday features of human interaction are precision tools that synchronize brains, strengthen social connection, and shape mental health.

When: June 23, 2026 | 7:30 pm
Where: Lensic Performing Arts Center, Santa Fe, NM.
Free tickets: https://t.co/TiZg8D5gbJ

Presented free to the public thanks to generous sponsorship by the McKinnon Family Foundation, with support from The Lensic Performing Arts Center and the Santa Fe Reporter.

[Bilu Huang @BiluHuang]

@acommanman766 @YouTube How to achieve system level reset?

[Bilu Huang @BiluHuang]

@tubedonmars @GerontologyMike https://t.co/yLTMSCvner

[Bilu Huang @BiluHuang]

https://t.co/ukkMGmxsik

[Bilu Huang @BiluHuang]

@tubedonmars @GerontologyMike https://t.co/dQcT2DUzdf

[Bilu Huang @BiluHuang]

The damage accumulation theory of aging is clearly incorrect because a valid theory cannot allow for contradictory evidence or loopholes. The DNA damage accumulation theory of aging is riddled with loopholes and can be determined to be wrong based on the following 22 evidences:

1. All human cells accumulate waste molecules like lipofuscin. In 1973, Tappel et al. added the free radical scavenger vitamin E to the feed of adult mice for one year and found that neuronal lipofuscin indeed decreased, but there was no reduction in mortality [Tappel A, Fletcher B, Deamer D. Effect of antioxidants and nutrients on lipid peroxidation fluorescent products and aging parameters in the mouse. J Gerontol. 1973 Oct;28(4):415-24. doi: 10.1093/geronj/28.4.415.]. Feeding mice a diet with 2% protein for 9-15 weeks led to the formation of large amounts of lipofuscin in the nervous system. Subsequently, feeding them a diet with 25% protein reduced lipofuscin [Monocha SL. Acta Histochen 1977;58:219.]. However, a high-protein diet actually shortens lifespan, indicating that cellular and individual aging are not caused by the accumulation of cross-linked, denatured waste molecules inside or outside cells.

2. In 2007, scientists at the University of Washington demonstrated that mitochondrial DNA mutations do not cause premature aging in mice. To observe whether point mutations (a single DNA base) in mtDNA directly affect aging, a research team designed "mitochondrial mutator" mice. Comparing the mtDNA mutation frequency between mutator mice and normal mice, they found that mutator mice had 50 times more mtDNA mutations but showed no signs of premature aging such as osteoporosis, hair loss, or decreased fertility [Vermulst M, Bielas JH, Kujoth GC, et al. Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet. 2007 Apr;39(4):540-3. doi: 10.1038/ng1988.].

3. In plants and animals without a specific immune system, cells with DNA damage mutations in the nucleus cannot be selectively cleared. For example, both planarian and tree somatic cells generate DNA damage, but planarians achieve immortality through fission reproduction and trees through branch cutting propagation, indicating that the DNA damage accumulation theory of aging is incorrect. The immortality of Turritopsis dohrnii is also unaffected by DNA damage.

4. In 1975, Wright and Hayflick replaced the nucleus of an aged cell with that of a young cell, resulting in the aged cell regaining youth and continuing to divide for the same number of divisions as the young cell [Wright WE, Hayflick L. Nuclear control of cellular aging demonstrated by hybridization of anucleate and whole cultured normal human fibroblasts. Exp Cell Res. 1975 Nov;96(1):113-21. doi: 10.1016/s0014-4827(75)80043-7.]. This shows that the determinant of cellular aging lies in the nucleus, not in the mutated mitochondria, lipofuscin, or various denatured and cross-linked waste macromolecules in the cytoplasm.

5. Compared to humans, cockroaches and tardigrades have superstrong DNA repair capabilities, but under suitable conditions, their lifespans are only a few months.

6. Radiation can cause DNA mutations. However, irradiating fruit flies with 45 Gy反而 resulted in a longer lifespan compared to the control group. If irradiation does not cause cancer, irradiating mice can also extend their lifespan.

7. At the individual level, mutated nuclear DNA (1) can be repaired; (2) if repair fails, apoptosis is initiated; (3) if neither repair nor apoptosis occurs, the cell is ultimately cleared by the immune system. Therefore, the increase in DNA-mutated cells with age is solely due to the aging of the immune system.

8. HeLa cells also rapidly accumulate non-telomeric DNA damage. However, HeLa cells still have an unlimited number of divisions.

9. Nuclear DNA mutations do not cause aging [Robinson, P.S., Coorens, T.H.H., Palles, C. et al. Increased somatic mutation burdens in normal human cells due to defective DNA polymerases. Nat Genet 53, 1434–1442 (2021).].

10. The number of mutations in aged yeast cells is quite low. Some genetically engineered mouse strains with high levels of free radicals or mutation rates do not seem to age prematurely nor have shorter lifespans than wild-type mice. This seems to indicate that mutation load (accumulation) may not influence aging as strongly as once thought.

11. The damage accumulation theory cannot explain the vast difference in lifespan between *C. elegans*, which lives only about ten days, and the Arctic clam, which lives 400–500 years. Why is the wear rate so different in the same environment? Why didn't clearing lipofuscin extend the lifespan of mice? Why is there such a huge difference in lifespan between neurons (which can last a hundred years) and white blood cells (which last only hours or days) within the same human body? Why does a variety of African killifish with a lifespan of only 3 months accumulate liver lipofuscin faster than a variety with a lifespan of 16 months, despite having similar body structures?

12. Long-lived cells like neurons and cardiomyocytes also demonstrate that damage accumulation can be overcome.

13. Cellular reprogramming phenomena, where aged cells can be reversed into young cells, also show that damage accumulation can be overcome.

14. No signs of aging are observed during growth and development. Since organisms can remain free from damage accumulation for extended periods during growth, continuously becoming stronger, if there were no mechanisms to overcome damage accumulation, there would be no reason for this trend to continue.

15. During mouse aging, the increased plasma proteins are mostly detrimental, while the decreased ones are mostly beneficial. If the damage accumulation theory holds, the compensatory overexpression of proteins triggered by damage accumulation should all be beneficial repair proteins. Furthermore, damage is non-directional, so the composition of plasma proteins should not change in a regular pattern, which contradicts the facts.

16. Autophagy in cells can clear damaged mitochondria and cross-linked, denatured macromolecules. But why do resveratrol and curcumin, which enhance autophagy, fail to extend mouse lifespan according to tests by the National Institute on Aging? Moreover, enhancing autophagy can accelerate ovarian aging in mice, and enhancing autophagy in the intestine or brain of *C. elegans* can shorten its lifespan.

17. The turquoise killifish, living in Africa and South America where waters can dry up at any time, has evolved a lifespan of less than 6 months, making it the shortest-lived vertebrate [Dance A. (2016). Live fast, die young. Nature, 535(7612), 453–455. https://t.co/RtK8fDPqwF]. Within its less than 6-month lifespan, it recapitulates various hallmarks of human aging: genomic instability appears, harmful mutations accumulate widely [Cui, R., Medeiros, T., Willemsen, D., Iasi, L. N. M., Collier, G. E., Graef, M., Reichard, M., & Valenzano, D. R. (2019). Relaxed Selection Limits Lifespan by Increasing Mutation Load. Cell, 178(2), 385–399.e20. https://t.co/UN9oRR0Pt8]; the thymus rapidly shrinks [Morabito G, Donertas HM, Seidel J, Poursadegh A, Poeschla M, Valenzano DR. (2023). Spontaneous onset of cellular markers of inflammation and genome instability during aging in the immune niche of the naturally short-lived turquoise killifish (Nothobranchius furzeri). bioRxiv 2023.02.06.527346; doi: https://t.co/tgVDj5wQAg]; telomeres shorten, cancer develops, regenerative capacity is lost, motor activity decreases, cognitive ability declines, etc. [de Bakker, D. E. M., & Valenzano, D. R. (2023). Turquoise killifish: A natural model of age-dependent brain degeneration. Ageing research reviews, 90, 102019. Advance online publication. https://t.co/K8qw1BNM9c]. Changes in gut microbiota during aging are similar to those in humans! Older fish have much lower bacterial diversity, closely correlated with their aging process [https://t.co/TQF2T9THEH].
Since turquoise killifish rapidly accumulate gene-mutated cells and develop cancer within less than 6 months, along with rapid changes in gut microbiota, it suggests that the accumulation of gene-mutated cells and cancer development are due to the aging of the immune system. Changes in gut microbiota are also caused by changes in intestinal secretions or, in other words, the aging of the intestine itself.

18. Taking killifish as another example, in Zimbabwe, where there are only brief rainy seasons followed by rapid drying of ponds, the killifish lifespan is only 3 months, matching the length of the rainy season. In Mozambique, where the rainy season is 4 times longer, the killifish can live for 9 months. Another killifish species living in an area with two rainy seasons can live up to 16 months. When these three types of killifish are raised under identical artificial conditions, their lifespan differences persist. This suggests that aging is program-controlled, not the result of random damage accumulation, because random damage accumulation cannot explain why the lifespans of these three congeneric fish (with extremely similar body structures) differ so greatly and "coincidentally" match the length of the rainy season.

19. Free radicals can increase DNA mutations and protein cross-linking/denaturation. However, in August 2015, a aging research center in California stated that free radicals actually play a crucial role in skin healing and healthy regeneration in people under 50. Scientists injected mice with excessive free radicals, expecting to see rapidly aged, wrinkled skin, but the opposite happened – the mice's skin actually improved. This indicates that DNA damage and protein cross-linking/denaturation are not the fundamental causes of aging.

20. Heterozygous mutation of mitochondrial superoxide dismutase (SOD2) in mice, while leading to increased oxidative damage, did not shorten the animals' lifespan [Van Remmen H, Ikeno Y, Hamilton M, et al. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics. 2003 Dec 16;16(1):29-37. doi: 10.1152/physiolgenomics.00122.2003.].

21. An article titled "Why Do We Age? DNA Damage A Likely Cause" [https://t.co/4fXfapZhph] suggests that DNA damage might be a cause of cellular aging because the gene expression patterns in cells exposed to DNA damaging agents are very similar to those in normal aging. Progeroid syndromes like Cockayne syndrome are also characterized by DNA damage.

22. Regarding the neurodegenerative diseases you mentioned, the mainstream approach to treating Alzheimer's disease is to eliminate Aβ and tau proteins through various methods. However, according to a 2018 report released by the Association for the Study of Pharmaceutical Manufacturers and Research in the United States, from 2000 to 2017, global pharmaceutical companies invested over $600 billion in Alzheimer's disease research and development, with over 300 clinically approved drugs failing, a failure rate exceeding 99%. This is also a major piece of evidence refuting the theory that aging is caused by  damage accumulation.

[Michael West @GerontologyMike]

I’ve been discussing, in a series of posts, the history leading up to the modern technology allowing the reprogramming of aging. After my PhD at Baylor College of Medicine I entered Medical School in Dallas. I had turned a family company called West Leasing Company into biotech enterprise I called Geron Corporation. In 1992, my third year as a student, I was approached by the Venture firm Kleiner Perkins who offered to finance the gamble that telomerase (if we could find the gene) would enable the extension (or even immortalization) of human cells and its inhibition could treat cancer. Some $30M later we still hadn’t found the gene. Remember, these were the days before DNA was fully sequenced. We were collaborating with Carol Greider at Cold Spring Harbor and Jim Watson and my board of directors were becoming impatient. Carol’s candidate gene in Tetrahymena went nowhere… Finally, Tom Cech’s lab told us of a candidate gene in Euplotes. We looked in our cDNA library and found a hit! In a hectic race to get the entire sequence and patent it, the scientists at Geron worked round the clock, sleeping in a trailer in the back of the building. To test if we had the real thing, I assembled, as I recall, five mortal cell RNAs and five immortal counterparts (four being cancer lines one being from the testicle (germ line). I can’t describe the electricity in the air. What a gamble we had bet on the telomere hypothesis and the search for the gene. The scientists didn’t know the order of the samples I gave them in order to blind the experiment, but I placed them in a logical order: five mortal cell RNAs, four cancer lines, then testis at the end. As the image slowly assembled on the phosphoimager, the sample on the end became visible, then with a collective gasp, we saw five blanks in the mortal and five positives on the right with the last one being the strongest (exactly what one would expect if we finally had the gene).

We then raced to express the gene in human mortal cells (cells from Len Hayflick’s leg being the first) and later a nice study published in Science in collaboration with Woody Wright that showed that indeed, telomeres were the clock behind the Hayflick limit and telomerase alone is capable of immortalizing cells.

This result overturned the long-held belief that the aging of cells was simply entropy at work, wear-and-tear, something we would never completely understand, and certainly something that we could never effectively stop. But for those of us that favored the programmed theory of aging, it was consistent with a mutation of a single letter in the DNA code leading to the premature aging seen in children with progeria and the common immortalization of cells in cancer.

Telomerase was never tested in humans because Geron became focused on telomerase inhibition for the treatment of cancer and in the stem cell program I will describe next. Hopefully in coming years, it will become part of a cocktail of agents that I will describe in future posts that leads to significant extension of human healthspan and lifespan. Below I post a picture of that team of scientists that worked so very hard to be the first to isolate the immortalizing gene telomerase.

[Bilu Huang @BiluHuang]

@GerontologyMike 👏👏Thank you for your amazing work!

[Bilu Huang @BiluHuang]

Hi Mike, human immortalized IMR90 lung fibroblasts expressing human papillomavirus (HPV) oncogenes E6 and E7 were cultured in vitro. Despite telomerase activation, telomere lengths were quantified via the high-precision telomere profiling method Telo-seq at population doublings of 66, 68, 71, 85, 96 and 106. The results revealed that the average telomere length decreased from 4294 bp at the 66th doubling to 2746 bp at the 106th doubling, with an average telomere shortening of 39 bp per cell division. This indicates that telomerase activation fails to maintain long telomeres and instead accelerates telomere shortening. The telomeres of immortalized cells are considerably shorter than those of normal cells, suggesting that cellular immortalization is independent of telomeres [199].

Overexpression of human telomerase reverse transcriptase (hTERT) in human dermal fibroblasts (HDFs) and human coronary artery endothelial cells (HCAECs) halted telomere shortening. Nevertheless, epigenetic age increased progressively with ongoing cell replication [171]. During in vitro culture of Syrian hamster embryo fibroblasts, telomere lengths remained stably at approximately 23 kb throughout cellular senescence [190], while DNA methylation was lost at a constant rate during continuous cell passaging [191].

These findings demonstrate that cellular immortalization is not associated with the maintenance of telomeres or DNA methylation. A plausible mechanism is that progressive shortening of rDNA arrays sustains elevated p53 levels; p53 in turn suppresses the expression of DNA methyltransferases, leading to continuous loss of DNA methylation.

Normal embryonic fibroblasts undergo 50 to 60 cell divisions. The so-called immortalized cell lines described above are not truly immortal, as they can only divide around 100 times at most before ceasing proliferation and eventually dying. In contrast, HeLa cells represent genuine immortalized cells, which have undergone nearly 20,000 divisions without exhibiting senescence.

[Bilu Huang @BiluHuang]

https://t.co/CJhzSetwBk

[Bilu Huang @BiluHuang]

@irat1onal @m_goes_distance 👏👏On the nose, Ira.