1119 replies to this topic

[Castiel]

Forgot to mention the near identical to resveratrol molecule pterostilbene is showing strong antiaging effects in topical skin treatment.

High dose oral pterostilbene adversely affects cholesterol, but topical can achieve high dose without such effects afaik

Scientists test an anti-aging cream that actually works
"Pterostilbene cream improved wrinkles, skin firmness, collagen, and pore size far better than a control emulsion. The results highlight pterostilbene as a promising natural ingredient for next-generation anti-aging skincare."
https://www.scienced...50914205851.htm

[QuestforLife]

I heard somewhere that telomere elongation can only occur during replication stage. Not sure if true and if this affects telomerase activation.
 

Yes, that's true, cells have to be in s-phase for the telomere to be accessible (*). 

But like so many things in biology it may not be an absolute rule. And this is where short telomeres being more easy to elongate come in, because the end is more accessible.

 

The telomere end is completely accessible during DNA-replication, as it has been unrolled. And it is completely inaccessible when folded up and tucked in. But in-between these two states there are situations where the telomere end has some accessibility, and this is enhanced with a short telomere because it is more difficult to tuck it in.

 

This is the proposed mechanism behind rejuvenation of old people using telomerase activators that are not strong enough to lengthen telomeres back to youthful length, but may be strong enough to take you back some of the way, or rather maintain an equilibrium point at some greater length than would otherwise be the case, with greater mortality than is optimal, but lower than it would otherwise have been.

 

It is virtually impossible to say how many years this might give you, or how much extra health span. But Bill Andrews is 73 and an endurance runner. He doesn't look young. And doesn't look to be getting any younger. But the does look much better than most his age. 

 

(*) It may be a mechanism for inhibiting telomerase activation as well, i.e. short telomeres have one telomerase blocking mechanism removed, but this is not confirmed.

 

Edited by QuestforLife, 17 September 2025 - 02:40 PM.

[Castiel]

Im still surprised asking chatgpt shows lack of lifespan telomerase experiments in vitro or in vivo for pterostilbene.

Given resveratrol effects and pterostilbene topical effects. It seems like a common sense conclusion is pterostilbene may be able to achieve similar easier.

Pterostilbene raises ldl at high dose, but the high doses would only be needed for a few weeks or months assuming it is as effective as resveratrol at activating telomerase. Given higher bioavailability and longer half life.

One would think someone would test pterostilbene for this in animals or at least in cells.

[QuestforLife]

Both resveratrol and pterostilbene are two-faced, they seem to inhibit or activate telomerase depending on dose and cell type. As far as I'm concerned, no one has yet figured out what their mechanism of action is, precisely. To me they always seemed like poisons that in certain circumstances end up being hormetic. 

[Castiel]

A recent article commenting on topical pterostilbene

https://www.popularm...-age-your-face/

It seems rejuvenating effects are observed if cells are exposed to high enough dose for long enough

[QuestforLife]

Summary of ‘Alternative Methods to Extend Telomeres’ Sept 2018 to Oct 2025

 

Early work on NAD+

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/#entry857309

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-2#entry868202

SIRT4

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-3#entry870174

Loss of NAD+ because of telomere shortening

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry900015

 

Work on Statin-Sartan protocol

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/#entry862269

link between ROCK inhibitors and telomerase

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/#entry864097

possible link with senolytics

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/#entry864534

using ROCK and mTOR inhibitors to reprogram brain cancer cells into normal neurons

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/#entry865160

How ROCK inhibitors block differentiation

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-4#entry878635

Feedback on protocol

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-5#entry881808

Summary of ROCK inhibition action on cells

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-6#entry883118

Attempts to come up with alternatives to statin and sartans

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-7#entry884915

Diagram of interventions

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry885663

Paper linking up ROCK and ECM

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry885731

ROCK and tgf-b

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry886244

Mean and Max lifespan extension with a ROCK inhibitor

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry896988

 

Work on telomerase activators and other important telomere papers

Royal Jelly

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-2#entry866228

Review of various activators

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-4#entry875566

Asiaticoside

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-5#entry880274

Some other telomeres studies

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-7#entry884556

Effect of antioxidant on telomere shortening in the bone marrow

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry885539

More on the same, later

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry896907

Telomere activators and CV diseases

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry885582

Telomere shortening predicts species life span

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-9#entry893160

using TERC upregulation to increase telomere length in stem cell

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry896804

Telomerase and Splicing Factor regulators

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-11#entry899109

T cells taking telomere length from other cells

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-11#entry899161

Do stem cell stimulants deplete the bone marrow pool?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry900006

Hyperbaric oxygen therapy

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry900378

Discussion of Blasco paper on hyperlong telomere mice

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/?view=findpost&p=901986

Discussion of actual in vivo rate of telomere attrition

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-14#entry902137

GDF11 lengthen telomeres in MSCs via TERC upregulation

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry903694

Possible benefit of Klotho to telomeres

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry903694

Nucleotides (specifically guanine) for elongation of telomeres: eat Anchovies and Herring!

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry904277

Blasco and short telomeres in kidney disease plus possible connection of short telomeres and the cancer causing epithelial to mesenchymal transition

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry904567

What is the most powerful telomerase activator and a comparison of methods of measurement

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry905188

Melatonin is the best antioxidant for telomeres?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905284

More on melatonin

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-18#entry906399

AKG and telomere length (in mice)

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905690

Discussion of a cell permeable, oxidation resistant form of Vit C and telomeres plus follow on discussion of ROS hormesis in some cell types

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905240

Various discussions on the bioavailability of Asiatic acid/asiaticoside (a purported telomerase activator) and why you may only want a very small dose

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-14#entry903398

Should we be taking Zinc for our telomeres?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry906002

Clear benefits to life expectancy, CVD and Cancer with longer telomeres: a study with 500k people

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry906042

Ability of endothelial cells to make new lining is telomere length dependent

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry906088

Caffeine promotes telomerase expression

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry906174

Dark chocolate for telomeres

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry906249

Alternatives to a telomere test: NLR and CRP

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-19#entry906563

Hyperfunctional telomerase: do you want more cell division or longer telomeres?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-20#entry907024

We should be aiming for mouse levels of telomerase, not HELA levels

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-20#entry907165

New intranasal and injectable gene therapy for healthy life extension

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry907730

New GDF11 telomerase paper in Nature:

Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry907939

Telomerase increases mitophagy through PINK1 - explanations for my increased exercise tolerance

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry908174

Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-22#entry908442

Telomere length and telomerase activity in T cells are biomarkers of high performing centenarians

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909206

Caffeine promotes the expression of telomerase reverse transcriptase to regulate cellular senescence and aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909654

Are the oncogenic effects of telomerase mediated by methyl transferases?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry910058

Loss of GDF11 shortens telomeres

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry911007

Does Berberine shorten telomeres?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry911030

Mitochondrial Telomerase Reverse Transcriptase Protects from Myocardial Ischemia/reperfusion Injury 

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry911292

Naringenin: super supplement?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry911334

NMN increases telomere length

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-25#entry912192

Has the telomere theory of aging been proven?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry915078

Telomerase is made in the nucleolus

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry915527

Telomerase protein levels as measured by immunohistochemistry are unreliable

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry915527

Telomere Shortening in Hematopoietic Stem Cell Transplantation: A Potential Mechanism for Late Graft Failure?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry916712

The flaws of methylation clocks 

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry916718

What is Tianshengyuan-1?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry917053

Supertelomerase!

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-27#entry917811

Final telomerase protocol

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-29#entry918979

Adding telomerase to symmetric division: a simplified model

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-29#entry919095

Spermidine

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry919793

Can ultrasound overcome replicative senescence?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920338

Should we take SAMe for telomeres?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920616

Can NO (nitric oxide) increase telomerase activity?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920756

DHA

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry921118

What is the optimal strategy for slowing telomere loss? It is not telomerase activators

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry923584

Oxidative Stress in Rat Hearts: a tale of exosomes

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-31#entry926109

IP6 shortens telomeres

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-32#entry927194

TERT without the TERC? Possible Manganese effects

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-32#entry927276

Where does the telomere theory of aging stand at present?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-33#entry928875

Is the epigenetic age acceleration caused by telomerase activators caused by nucleotide depletion?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-33#entry929114

More proof that manganese is good for telomeres

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-33#entry929333

A four year intervention study with six years follow up shows selenium and CoEnzyme Q10 prevents telomere shortening in leukocytes and reduces mortality

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-33#entry929421

Main telomerase activation protocol 

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry930746

High dose cycloastragenol 

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry931370

Stunning confirmation of my theory that epitalon does not activate the telomerase gene

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry931389

TERT activation targets DNA methylation and multiple aging hallmarks

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry931663

The interesting idea of exosomes full of telomerase to treat ageing

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry932186

Nicotine is Amazing!

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-34#entry932495

Telovital

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-37#entry936295

 

View of Aging

Importance of cell size

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-4#entry877909

The Selfish Cell lives longer

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-5#entry880039

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-5#entry880339

Telomeres are NOT passive in aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-6#entry883065

Discussion of telomeres and cancer

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-9#entry892745

Senescence and Cancer, again

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry897658

Are methylation changes with age evidence of a program?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-12#entry899778

Comments on heterochronic parabiosis

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry900319

More on Selfish Cell theory of aging (2021)

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-14#entry902349

Age related methylation and the connection with the Selfish Cell Theory of Aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905284

Plus why aging is cancer

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905627

Putting together telomere and hyperfunction theories of aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-20#entry907460

Oxidative stress alters global histone modification and DNA methylation

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry908138

How non-differentiating Selfish (stem) cells come to dominate the stem cell pool; links between methylation, telomerase and ROS

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry908160

Finding the Culprit: the hormones required for sexual maturity may be the trigger that starts aging via downregulation of TET2

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-22#entry908266

Discussion over whether methylation of gene promoters is protective against stem cell loss and the counter evidence: immortalised cells accumulate such methylation

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-22#entry908322

Discussion of the combined use of telomerase activators, GDF11, AKG, vit A and C

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-22#entry908398

Summing up the Twin Evils of aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-22#entry908458

The Evolution of the Selfish Cell

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909231

Cancer and the Selfish Cell

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909457

Does the Selfish Cell imply programmed or accidental aging?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909533

Finding the Culprit II: Species' cellular ROS level sets aging rate via down regulation of demethylases and failure of Circadian Rhythm

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909696

How does the Selfish Cell affect post-mitotic cells?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909914

Why long telomeres won’t make you live forever, but short telomeres mean you’ll die young

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry910244

Defining the steps that lead to cancer

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry910636

What are epigenetic Aging tests actually measuring?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-25#entry912768

A new thesis

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-25#entry914358

The Secret to lengthening telomeres in all cells

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry915113

The Tortoise and the Hare

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry915479

Hyperfunctional Telomeres Part II

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-26#entry916386

Paving the way for the 'speeding car': Explaining the benefits of long telomeres in the context of mTOR

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-27#entry917560

Just how much can we inhibit mTOR?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-27#entry917637

A reanalysis of some epitalon studies and a new take on the DNA mutation theory of aging

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920453

Are we being poisoned?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920902

My current thoughts on aging, October 2023

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-31#entry926803

 

 

 

Skin aging

Stem cell competition – can you have too much symmetrical division?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-4#entry879560

 

Results

Methylation results from Statin-Sartan protocol

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-3#entry873678

Telomere length improvements via Lifelength

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-6#entry883063

PhenoAge improvements

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-6#entry883130

Epitalon increases methylation age and discussion

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-8#entry892505

Further discussion

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-11#entry899397

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-11#entry899496

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-12#entry899538

Plan to reduce both telomere and methylation age

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-9#entry895170

No improvement in methylation age from 3 months of AKG

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry896760

Improvement in methylation age from 6 months of AKG

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry899822

Further improvement in epigenetic age (-6.6 years)

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-14#entry903105

Summary of GDF11 experience with biomarkers

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-15#entry905149

May 2021 Methylation age results

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-20#entry907470

Discussion of reaction times on GDF11

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry908189

October 2021 Trume Results

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry910821

Amino Acid results: Do telomerase activators deplete glutamine?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-24#entry911858

February 2022 Trume Results

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-25#entry914327

Is it time to abandon methylation based aging tests?

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry920081

Results: March 2023

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry922301

a theory for why epigenetic aging is transitory:

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-30#entry922401

 

Sundry

Fatty Acid Oxidation

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-10#entry896447

Starvation and stem cell renewal

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-13#entry899839

See other thread:

Feeding stem cells: the strange case of dietary restriction and alpha lipoic acid

https://www.longecity.org/forum/topic/108288-feeding-stem-cells-the-strange-case-of-dietary-restriction-and-alpha-lipoic-acid/#entry885897

Possible use of pioglitazone with telomerase activators to increase subcutaneous fat without bladder cancer risk

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-14#entry902929

Resveratrol is weird.

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-16#entry905283

Demethylating the klotho promoter with hydrogen sulphide

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-17#entry905925

Melatonin is linked to mitochondrial function and increases TET2 production

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-21#entry908191

Discussion starting here on reversing thymic involution

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-23#entry909243

Comment on gonadal rejuvenation by GDF11

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-25#entry913693

Mitochondrial hyperfusion via metabolic sensing of regulatory amino acids

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-27#entry918095

Immortalizing Cells for human consumption

https://www.longecity.org/forum/topic/102169-alternative-methods-to-extend-telomeres/page-33#entry927611

 

[dlewis1453]

Great compilation QuestForLife! Thanks for all the time you spend meticulously documenting your research and sharing your results with us. I've been very busy with life in 2025 and haven't had much time to post, but I still eagerly read all of your updates.

 

I'm curious if you are still using stearic acid as a fat burning agent? I'm considering starting a cocoa butter protocol to try to burn fat and gain muscle at the same time. 

[QuestforLife]

 

I'm curious if you are still using stearic acid as a fat burning agent? I'm considering starting a cocoa butter protocol to try to burn fat and gain muscle at the same time. 

 

The answer is no. I haven't used Stearic acid for some time. 

 

I now only use DHM to encourage fusion and also - the bounce back from glucose to fat burning you get when you use niacin. I find that metabolic health is the easiest and most effective longevity level to pull, and this can be done effectively with niacin. 

[Castiel]

Consulted with gpt and it believes the resveratrol study showing human cell rejuvenation was through alt mechanisms not through telomerase activation, given the cells involved don't express telomerase.   So if resveratrol can activate alt at high doses in normal aged cells, it is conceivable other compounds may also activate alt and lengthen telomeres.

[Advocatus Diaboli]

Re: Post  1119

 

Edited note--the formatted table in point 3, below, was damaged when inserting into this post.

 

DeepSeek says:

 

Conclusion

 

"It is conceivable and probable that certain compounds—particularly those that degrade ATRX, inhibit DNA repair, or modulate recombination—could create cellular conditions that permit or promote the ALT pathway in susceptible cells. However, this would be a dangerous and undesirable effect for healthy tissue, akin to promoting carcinogenesis.

The more relevant and active field is discovering compounds that lengthen telomeres via telomerase activation or slow their attrition, and separately, discovering compounds that specifically kill ALT-dependent cancer cells by inhibiting the pathway.

If your interest is in healthy aging, the focus should be on the former (telomerase/telomere maintenance), not on the cancer-associated ALT pathway."

 

 

The full answer to the prompt (taken from post 1119) "is conceivable other compounds may also activate alt and lengthen telomeres." is:

Excellent and sophisticated question. This ventures into cutting-edge molecular biology and aging research. The short answer is:

Yes, it is highly conceivable, and there is active research in this area. However, the relationship is complex, nuanced, and importantly, activating the ALT pathway is generally not a desired goal for healthy aging.

Let's break this down.

1. Understanding ALT vs. Telomerase

First, a crucial distinction:

• Telomerase is the enzyme that naturally maintains telomeres in stem cells, germ cells, and, problematically, in ~85-90% of cancers. It adds telomeric DNA directly.

• ALT (Alternative Lengthening of Telomeres) is a recombination-based mechanism used by ~10-15% of cancers (common in sarcomas, glioblastomas, and certain carcinomas) and some immortalized cell lines to maintain their telomeres without telomerase. It is characterized by heterogeneous telomere lengths, telomeric DNA copying between chromosomes, and special structures called ALT-associated PML bodies (APBs).

2. Could Compounds "Activate" ALT in Normal Cells?

This is the core of your question. In theory, yes, but with major caveats.

• The Trigger: ALT activation in cancer usually occurs after the cell has already become cancerous and has lost normal cell cycle controls (often via p53 and Rb pathway inactivation). It is a survival mechanism for those rogue cells.

• Hypothetical Pathway: A compound could, in principle, induce the conditions that favor ALT by:

  1. Severely disrupting normal telomere maintenance (e.g., chronically inhibiting telomerase in a cell that relies on it).

  2. Inducing DNA damage and recombination at telomeres (e.g., through compounds that cause telomere-specific oxidative stress or replication stress).

  3. Dysregulating the proteins that suppress ALT in normal cells (e.g., proteins involved in the ATRX/DAXX chromatin remodeling complex, whose loss is a hallmark of ALT-positive cancers).

• The Reality: Deliberately inducing ALT in a normal, healthy cell would likely be highly mutagenic and carcinogenic. You would be pushing the cell toward a cancer-associated, genetically unstable state.

3. Compounds That May Indirectly Influence Telomere Length or ALT Status

Research has identified substances that affect telomere biology, some of which might tip the balance in cells already on the cusp of using ALT. None are straightforward "ALT activators" for therapy.

 

 

Compound/Class Proposed Mechanism Effect on Telomeres Relevance to ALT Cereblon Modulators (e.g., some immunomodulatory drugs) Degrade proteins like ATRX (a major ALT suppressor). Could potentially induce ALT-like features in cells where ATRX is degraded. Direct. This is a prime example of a compound that could theoretically enable ALT by removing a key blocker. DNA Damage Response (DDR) Inhibitors (e.g., ATR inhibitors) Impair the cell's ability to repair DNA, including at telomeres. Cause telomere dysfunction and replication stress. Indirect. Could create the genomic instability that promotes recombination-based telomere maintenance (ALT). Recombination Modulators Affect homologous recombination (HR) pathways. Could either promote or inhibit telomeric recombination. Direct. Modulating HR is at the heart of the ALT mechanism. Oxidative Stress Agents Increase reactive oxygen species (ROS). Cause telomere shortening and damage, potentially triggering a crisis. Indirect. Could be a first step in forcing a cell to seek an alternative survival mechanism like ALT. G-quadruplex Stabilizers (e.g., BIBR1532, Telomestatin) Stabilize the G-quadruplex structures in telomeric DNA, blocking telomerase. Initially shorten telomeres; in cells without telomerase, can trigger crisis. Indirect. By inhibiting telomerase, they might select for the outgrowth of any pre-existing ALT cells in a population.

4. The Therapeutic Paradox & Future Directions

The intense research focus is not on activating ALT, but on targeting and inhibiting it to kill ALT-positive cancers.

• ALT Inhibitors are being sought to treat the cancers that rely on this pathway. Potential targets include proteins essential for ALT (e.g., BLM, MUS81, SLX4, PML) or the unique chromatin state of ALT telomeres.

• For Healthy Aging: The goal is telomere maintenance, not ALT activation. Research here focuses on mild telomerase activators (e.g., TA-65, a cycloastragenol derivative), lifestyle factors (diet, exercise, stress reduction), and other compounds (astragalus extracts, marine omega-3s) that may slow attrition through antioxidant or anti-inflammatory effects.

Conclusion

It is conceivable and probable that certain compounds—particularly those that degrade ATRX, inhibit DNA repair, or modulate recombination—could create cellular conditions that permit or promote the ALT pathway in susceptible cells. However, this would be a dangerous and undesirable effect for healthy tissue, akin to promoting carcinogenesis.

The more relevant and active field is discovering compounds that lengthen telomeres via telomerase activation or slow their attrition, and separately, discovering compounds that specifically kill ALT-dependent cancer cells by inhibiting the pathway.

If your interest is in healthy aging, the focus should be on the former (telomerase/telomere maintenance), not on the cancer-associated ALT pathway.

 

 

 

Edited by Advocatus Diaboli, Today, 06:48 AM.