Why telomeres shorten and restoration strategies in aging

Telomeres are DNA repeats found at the ends of chromosomes. They serve to maintain chromosomal stability. The caveat is that they shorten each time the cell divides due the end replication problem. That is, unless the cell expresses telomerase. Telomerase is a ribonucleoprotein complex (a complex containing protein and RNA) that can add back telomeric repeats.

So what happens if telomerase isn't expressed? Well, after ~50 divisions the shortened telomeres induce a cellular state known as replicative senescence. Basically, the cell stops dividing. This is thought to be beneficial since it acts as a tumour protective mechanism by preventing uncontrolled cells from replicating too many times. However, it can also reduce the regenerative potential of tissues.

Senescent cells accumulate with age. Moreover, a weak negative correlation is also seen between age and telomere length.

For these reasons there is much interest in using telomere restoration strategies to target aging and for treatments people suffering with telomeropathies. But how would this be achieved and would it pose a cancer risk?

In this video we will address these questions and provide the details of why telomeres shorten with age and how the length could be restored.

TIMESTAMPS
Intro - 00:00
Why telomeres shorten - 00:45
Telomerase - 03:20
Cellular senescence & Hayflick limit - 04:30
Aging link (organismal/mouse studies) - 06:00
Telomere restoration strategies - 08:15

REFERENCES

[TheSheekeyScienceShow]

I think there is much still to learn about telomeres but I hope this video has given a good overview of our current understanding. p.s who doesn't love the shelterin complex!? :D

[gamblinguru]

Just wanted to say thanks for making these amazing videos. The longevity movement is lucky to have you on its side. I'm not sure if you saw the in vitro study of telomerase-inducing compounds, but a blend of Astragalus, Rhodiola rosea, broccoli seed extract, and vitamin D was significantly more powerful than TA-65 at increasing telomerase.

[rylaczero]

Been subscribed to your channel for some weeks. The quality and delivery of content is top notch. I am not of Molecular Biology background but interested in it since I age. The genome is a latent space representation from my perspective and might help in gaining some insights without doing actual experiments that take time.

[danno]

Great job explaining telomeres — thanks very much!

[schuggy]

This understanding is the key to the real fountain of youth. We're on the verge of something very cool in the human species. We need make some real big cultural adjustments very soon, because it's about to get real-real.

[JazenValencia]

Chinese Astragalus (cheap)is where they get (expensive) TA-65, and the Astragalus works better. The peptide Epitalon, also under the name Epithalon lengthens Telomeres. 5 to 10 mg/day for 10 to 14 days typically once a year.

[daveoatway]

Very nice description of a complex process. Best I've seen. Thank you

[drkmlakshmipathy]

Wonderful presentation..I have seen first of this kind ....very scientific and illustrative too..lots of regards from Chennai India

[elba_magellan]

awesome vid, love the illustrations and lucid explanation

[keng]

I really love your videos and your deep exploration into these aging and health related discussions! Also, I like your accent as you are a joy to listen to! Thank you!

[JenMarco]

Awesome video! I usually have to watch videos at high speed but this was perfect!

[aclearlight]

Great work! Thank you so much for going deep...this chemist salutes you!

[mr.e]

11:00 Would you be able to make a type of telomerase that can spot the difference between healthy cells and cancer cells? Maybe do this via the therapy delivery mechanism?

[pavelbaidurov]

Cancer goes up with thymus shrinking. And If you restore Thymus - it will be ok to restore telomeres?

[monnoo]

good overview.
small glitch: the hyflick limit is oudated... it was deteremined only in one or 2 cell types, in vitro. On the level of tissues it is much higher and different tissues have a very different limit. Skin cells replicate much more often

[saraassar]

Very informative and easy to understand. Thanks

[sciencesimplified]

I dont believe telomerase activity will stimulate cancer growth and there is no causal evidence support this fear. Cancers have unregulated cell growth, and this growth requires telomerase activity. However, supporting telomerase activity has no effect on stimulating unregulated cell growth(as far as we know and there is no reason to believe otherwise, although of course anything is possible). Telomerase activity is used by cancers yes, but if you give a healthy cell with regulated cell growth telomerase, this wont suddenly trigger aberrant activation of the cell cycle, it will simply allow the cell grow uncontrollably if it already has the genetic mutations necessary for uncontrolled cell growth. Honestly, it probably is pushing a dysfunctional cell one step closer to being immortal and this is a concern and the transient idea is interesting and theoretically abrupt supplementation to TA65 should seize growth. This was a well designed video great data.. personally I feel comfortable taking TA-65 but perhaps you're right to heavily weigh safety when there are so many unknowns

[chrisdonner]

Dr. Cooke's mRNA work is incredible. "Dr. John P. Cooke is the Chair of the Department of Cardiovascular Sciences at the Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration, and Medical Director of the RNA Therapeutics Program in the Houston Methodist DeBakey Heart and Vascular Center in Houston, Texas."

[willofdodge]

WOW, You are so smart. I hope you go on Joe Rogan Podcast one day

[PravinPatil]

I read somewhere that fasting helps. Does it?