Lifeboat Foundation

To evaluate the accuracy of the models²⁸, we sampled from the BNN or deep ensemble to determine their uncertainty predictions (Extended Data Fig. 3a, b). Correct predictions are oriented toward the lower and higher range of the output, representing greater certainty about samples’ states, whereas incorrect predictions tend towards the 0.5 threshold. We can therefore assume higher confidence in a model’s predictions by removing the predictions in the middle using thresholds. We evaluated a range of thresholds with several models (Extended Data Fig. 3c–f), which show a substantial increase in accuracy due to the ambiguous samples being discarded, including the ensemble of normalized models reaching accuracy of 97.2%. A similar approach was applied to other models, including the IR and RS models (Extended Data Fig. 3g, h), raising accuracy by 10–15%, although this reduces the number of cells considered.

To better understand the development of the senescent phenotype and how nuclear morphology changes over time, we analyzed human fibroblasts induced to senescence by 10 Gy IR and imaged at days 10, 17, 24 and 31. The predictor identifies senescence at all four times points with probability that increases from days 10 to 17 but declines by day 31 (Extended Data Fig. 4a). Interestingly, examining the probability distribution of the predictor it was apparent that a growing peak of nonsenescent cells appear after day 17, suggesting that a small number of cells were able to escape senescence induction and eventually overgrow the senescent cells (Extended Data Fig. 4b). Indeed, when investigating markers of proliferation, we see that over the time course, PCNA declines until day 17, after which the expression starts to return (Extended Data Fig. 4c). p21^Cip1 follows an inverse pattern with stain intensity increasing initially and then declining slightly by day 31 (Extended Data Fig. 4D). We also saw a decrease in DAPI intensity for days 10 and 17, indicating senescence, but a reversion to control level by day 31 (Extended Data Fig. 4e). To confirm that the predictor accurately determined senescence even 31 days after IR, we evaluated if markers of proliferation and senescence correlated with predicted senescence. Accordingly, cells with predicted senescence had higher p21^Cip1 levels, lower PCNA and lower DAPI intensities and vice versa (Extended Data Fig. 4f–h). Morphologically, area and aspect are higher for predicted senescence, whereas convexity is lower (Extended Data Fig. 4i–k). Finally, a simple nuclei count confirms growth, following IR treatment (Extended Data Fig. 4l). Overall, the senescence predictor captures the state during development in agreement with multiple markers and morphological signs.

Senescent cells are associated with the appearance of persistent nuclear foci of the DNA damage markers γH2AX and 53BP1 (refs. ^31,32). Our base data set including control, RS and IR lines were examined for damage foci using high-content microscopy, where we found the mean count for controls to be below 1 for each marker, whereas RS had 4.0 γH2AX and 2.0 53BP1 foci and IR had 3.4 γH2AX and 3.0 53BP1 foci (Fig. 4a, b and Extended Data Fig. 5a). We calculated the Pearson correlation between predicted senescence and γH2AX and 53BP1 foci counts and found that across all conditions, there is a moderately strong correlation of around 0.5 (Fig. 4c). This association is also visible when simply plotting foci counts and senescence prediction, which shows predicted senescence flipping from low to high, along with shifts in foci counts (Extended Data Fig. 5b). Our feature reduction masked internal nuclear structure, but it is nonetheless notable that senescence prediction correlates with foci count. We also compared the correlation between predicted senescence and area, where we see a correlation of around 0.5. In sum, there is a considerable correlation between foci counts and senescence.

AgeX Therapeutics, a preclinical biotech looking to turn back the clock on aging, may have to wind down, announcing “substantial doubt” about its ability to continue as money runs dry and debts mount.

The California biotech made $12,000 in revenue for the second quarter and recorded $1.6 million in operating expenses over the same period, according to financial results posted August 12.

During the first quarter, the biotech borrowed the final half million of credit available under a 2020 agreement with Juvenescence—a separate anti-aging biotech—and entered a new deal in which Juvenescence will provide $13.2 million in credit for a year. AgeX drew an initial $8.2 million of the line of credit and used $7.2 million to refinance the principal and the loan origination fees under a 2019 loan agreement with Juvenescence.

Circa 2021 immortality of the pancreas by inducing pluripotent cells of the pancreas.

A microwell chip facilitates the single-cell characterization of the differentiation of aggregates of human induced pluripotent stem cells into pancreatic duct-like organoids and the discovery of secreted markers of pancreatic carcinogenesis.

Circa 2000

Immortal epithelial cell lines were previously established after transduction of the HPV16-E6E7 genes into primary cultures of normal pancreatic duct epithelial cells. Single clones were isolated that demonstrated near normal genotype and phenotype. The proliferation of HPDE6-E6E7c7 and c11 cells is anchorage-dependent, and they were nontumorigenic in SCID mice. The cell lines demonstrated many phenotypes of normal pancreatic duct epithelium, including mRNA expression of carbonic anhydrase II, MUC-1, and cytokeratins 7, 8, 18, and 19.

August 9, 2022 – A new national poll of registered voters in the United States demonstrates broad bipartisan support for advancing research into longevity treatments that would extend healthy human lifespan.

The signaling protein, known as mTOR, is excessively active in many cancer cells and plays a key role in various diseases, such as diabetes, inflammation, and aging. Meanwhile, autophagy is well-known for its elaborately mediated regulation of activity by the mTOR protein in cells. Inhibiting this activity of the mTOR protein can increase autophagy and subsequently induce cancer cell death.

Professor Kim Se-yun’s research team conducted a study on developing an mTOR-inhibitory anticancer drug with a drug regeneration strategy based on effective binding technology that models physical interactions between compounds and target proteins using the three-dimensional protein structure.

Drug regeneration finds new indications for FDA-approved drugs or clinical drug groups previously proven safe. According to the researchers, this strategy can innovatively shorten the enormous time and investment in new drug development that traditionally takes more than 10 years.

Researchers at the Hebrew University of Jerusalem have discovered a new family of molecules that enable cells to repair damaged components, making it possible for those tissues to retain proper function. The efficacy of the molecules was demonstrated on a model organism – the C. elegans roundworm. The research team examined the effect of various therapies on longevity and quality of life, and successfully showed they can protect the worm and human cells from damage.

The researchers, led by Professors Einav Gross and Shmuel Ben-Sasson, have founded a company called Vitalunga to advance the research and translate it into therapeutics.

Longevity. Technology: A major factor in aging tissues is the reduced effectiveness of our cell’s quality-control mechanism, which leads to the accumulation of defective mitochondria – the cellular ‘power plants’ responsible for energy production. Mitochondria can be compared to tiny electric batteries that help cells function properly. Although these ‘batteries’ wear out constantly, our cells have a sophisticated mechanism called mitophagy that removes defective mitochondria and replaces them with new ones. However, this mechanism declines with age, leading to cell dysfunction and deterioration in tissue activity, and is implicated in many age-related diseases, such as Alzheimer’s disease, Parkinson’s disease, heart failure and sarcopenia.

Why do some animals live longer than others?

Is aging inevitable, like the rusting of a tin can, or in some sense preprogrammed?

The answers to these questions could drastically improve human health. My latest piece for BioViva Sciences is a concise overview of the comparative biology of aging.

Continue reading “Why We Age” »

It’s a question that keeps some scientists awake at night: Do spiders sleep?