Lifeboat Foundation

Telomerase defers the onset of telomere shortening and cellular senescence by adding telomeric repeat DNA to chromosome ends, and its activation contributes to carcinogenesis. Telomerase minimally consists of the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR). However, how telomerase assembles is largely unknown. Here, we demonstrate that PES1 (Pescadillo), a protein overexpressed in many cancers, forms a complex with TERT and TR through direct interaction with TERT, regulating telomerase activity, telomere length maintenance, and senescence. PES1 does not interact with the previously reported telomerase components Reptin, Pontin, p23, and Hsp90. PES1 facilitates telomerase assembly by promoting direct interaction between TERT and TR without affecting TERT and TR levels. PES1 expression correlates positively with telomerase activity and negatively with senescence in patients with breast cancer. Thus, we identify a previously unknown telomerase complex, and targeting PES1 may open a new avenue for cancer therapy.

Telomerase is a ribonucleoprotein (RNP) enzyme that adds telomeric repeat DNA to chromosome ends (1–3). This prevents progressive shortening of telomeres caused by the failure of the DNA replication machinery to duplicate the very end of each chromosome. Once telomeres are shortened to a certain length, cells enter replicative senescence or, alternatively, undergo apoptosis, a major tumor-suppressive mechanism. Telomerase, which is required for de novo telomeric repeat DNA synthesis and telomere maintenance, is expressed in approximately 90% of cancer cells but undetectable in the majority of normal somatic cells (4–6). Thus, telomerase is thought to be a relevant factor in distinguishing cancer cells from normal cells and has become a target for cancer therapy.

Telomerase is minimally composed of the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR). Studies have shown in vitro assembly of active telomerase by combining the purified RNA component with the TERT synthesized in rabbit reticulocyte extract (7–9). A few accessory proteins have been identified to associate with the active telomerase RNP complex. The molecular chaperones p23 and Hsp90 bind to human TERT (hTERT), and chemical inhibition of Hsp90 decreases telomerase activity (10, 11). However, determining whether Hsp90 is required for active telomerase assembly is difficult because chemical inhibition of a key chaperone in human cells potentially has pleiotropic and indirect effects. Assembly of human TR (hTR) and hTERT into catalytically active telomerase is facilitated by the adenosine triphosphatases Reptin and Pontin (12). Pontin knockdown (KD) reduces telomerase activity and hTR levels.

A new unique signal discovered within the brain might be what makes us human:

https://science.sciencemag.org/content/367/6473/83

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Continue reading “Dendritic action potentials and computation in human layer 2/3 cortical neurons” »

Years of investment in basic science of cancer therapeutics are “starting to pay off,” an expert said.

The pathogen has been newly identified in eight cases of encephalitis in Germany over the past 20 years.

Stephen Hawking passed away on 14 March 2018. His work changed literally everything we know about the cosmos and our place in it. But his greatest contribution to our species wasn’t his theories on black holes or how quickly the universe was expanding, it was his humanity.

Professor Hawking was born on 8 January 1942. He would have been 78 years old today – a bit older than ‘boomer’ age, his generation was called the “Silent” one. In his early twenties he was diagnosed with Lou Gehrig’s disease (ALS). Eventually he became paralyzed and could only speak with the assistance a computer-generated audio device.

If this works that would be awesome.

It is estimated by The National Kidney Foundation that over 100,000 patients are on the waiting list for kidney donors. A further 3,000 names are added to the list every year. An average patient has to wait for 3.6 years for a viable transplant. The patients are treated with dialysis while they are waiting for a transplant and only one in three patients survive for more than five years without a transplant. All that could change as scientists have developed the world’s first artificial kidney.

Continue reading “This Artificial Kidney Eliminates The Need For Kidney Dialysis” »

STEM Bootstrapping in Bio-Medicine! — On this recent ideaXme (https://radioideaxme.com/) episode, I was joined by 24 year old Malawian inventor, Sanga Marcarios Kanthema, founder and CEO of two companies, Dolphin Health Innovations and QubiX Robotics, who’s bringing health tech innovations to one of the world’s poorest countries — #Ideaxme #Malawi #Robotics #EKG #Stethoscope #Prosthetics #MobileHealth #SmartPhones #Telemedicine #MedicalDrones #Health #Wellness #Longevity #IraPastor #Bioquark #Regenerage

Ira Pastor, ideaXme exponential health ambassador and founder of Bioquark, interviews Sanga Kanthema, 24 year old electronics specialist and founder and CEO of two Malawi-based companies, Dolphin Health Innovations and QubiX Robotics.

Continue reading “How To Innovate In Biomedicine With Limited Resources For Big Results” »

US$30 Million to Seed Hundreds of Bold, Innovative Ideas for Human Longevity! — On this ideaXme (https://radioideaxme.com/) episode, I am joined by Dr. Victor Dzau, President of the U.S. National Academy of Medicine (https://nam.edu/initiatives/grand-challenge-healthy-longevity/) to talk about the potential of their Healthy Longevity Global Grand Challenge — eNag #ideaXme #VictorDzau #Wellness #Health #NationalAcademyOfMedicine #NAM #NAS #NIH #FDA #Duke #Cardiology #Longevity #Biotechnology #Regeneration #LifeExtension #Aging #Challenges #Prizes #Competitions #IraPastor #Bioquark #Regenerage

Ira Pastor, ideaXme exponential health ambassador and founder of Bioquark, interviews Dr. Victor Dzau, President of the United States National Academy of Medicine (NAM)and of the United States National Academy of Sciences (NAS).

Continue reading “A US $30 million fund to promote bold ideas for aging populations: Dr Victor Dzau” »

7-Ketocholesterol is a harmful oxidized byproduct of cholesterol, it is highly toxic with no redeeming qualities and serves no purpose in our bodies aside from allowing heart disease to develop. Check out Underdog Pharma’s recent review at Science Direct to learn more!

Oxidative stress has long been causatively implicated in the aging process [219,220]. As described in section 2, 7KC is the most common stable product of a reaction between cholesterol and a free radical. This is a vicious cycle as 7KC also leads to increased free radical production and release, seemingly by plasma membrane permeabilization. As discussed above, mitochondrial dysfunction and free-radical formation are also strongly implicated in the aging process and so while the precise mechanistic links between mitochondria, 7KC, and aging are still being elucidated they seem likely to be intertwined.

Is 7KC a biomarker of aging? As discussed in section 4, 7KC accumulation is directly implicated in many diseases of aging, including atherosclerosis, heart failure, AMD, NAFLD, and AD. It is thus reasonable to hypothesize that when otherwise unrelated diseases of aging share a common cause, that this cause is likely to be a part of the biological aging process. 7KC is known to accumulate in phagocytic cells such as macrophages (promoting the formation of foam cells), RPE cells, and microglia. It has also been suggested that c. elegans subjected to 7KC could be a good model of 7KC-dependent aging [221]. As 7KC is broadly toxic, and most cells seem to have difficulty metabolizing it, it may be that, with age, 7KC is bioaccumulating and impairing functional activity of the cells and tissue.

Continue reading “7-Ketocholesterol in disease and aging” »