Lifeboat Foundation

Advanced age is a shared risk factor for many chronic and debilitating skeletal diseases including osteoporosis and periodontitis. Mesenchymal stem cells develop various aging phenotypes including the onset of senescence, intrinsic loss of regenerative potential and exacerbation of inflammatory microenvironment via secretory factors. This review elaborates on the emerging concepts on the molecular and epigenetic mechanisms of MSC senescence, such as the accumulation of oxidative stress, DNA damage and mitochondrial dysfunction. Senescent MSCs aggravate local inflammation, disrupt bone remodeling and bone-fat balance, thereby contributing to the progression of age-related bone diseases. Various rejuvenation strategies to target senescent MSCs could present a promising paradigm to restore skeletal aging.

Nanomedicine uses nanomaterials [e.g., carbon nanotubes (CNTs), nanoparticles, and nanodiscs] or organic nanostructures (e.g., DNA origami and liposomes) for drug delivery (8–10), medical imaging (11–14), and tissue regeneration (15). Nanomaterials offer therapeutic efficacy through their tissue permeation, interaction with an external energy source, and capability to be combined with other therapeutic modalities (16, 17). Because we recently demonstrated that GBM cells are mechanosensitive (18), we set to use nanomaterials to develop a nanoscale mechanical approach to treat GBM. Mechanical perturbation has been investigated as an approach to target cancer cells. For example, magnetic field–actuated nanomaterials compromise the integrity of plasma membrane, leading to the death of in vitro–cultured GBM cells (19) and breast cancer cells (20). GBM cells, which were preincubated with magnetic nanoparticles, were implanted into mice to generate xenograft tumors. A rotating magnetic field, which was then applied to these magnetic particles–harboring tumors, suppressed GBM growth (21). Similarly, magnetic field mobilization of mitochondria-targeting magnetic nanoparticle chains demonstrated efficacy in inhibiting GBM growth in mice (22). While these studies showed that magnetic field–controlled nanomaterials can be used in cancer treatment, the utility of magnetic nanomaterials in treating chemoresistant tumors, the root cause of tumor relapse and patient death, remains unexplored.

GBM displays an extreme level of heterogeneity at genomic, epigenetic, biochemical signaling, and cellular composition levels (23). The heterogeneous nature of GBM confers treatment resilience to tumors and leads to a unifying therapy resistance mechanism; i.e., suppressing selected proteins or biochemical pathways provides a fertile ground for alternative signaling mechanisms, which are not targeted by the given therapy, to fuel GBM growth (24). In other words, the “whack-a-mole” approach failed to benefit patients with GBM for decades. For this reason, we hypothesized that nanomaterial-based mechanical treatment of cancer cells, rather than specific targeting of signaling pathways, can overcome the therapy resistance of this biologically plastic disease. To this end, we engineered a mechanical nanosurgery approach using magnetic CNTs (mCNTs; nanotubes with carbon surface and a cavity filled with iron particles) based on the following reasons.

A large case-control study by international researchers at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan has found that people who carry certain genetic risk factors for gastric (stomach) cancer have a much greater risk if they have also been infected by the bacterium Helicobacter pylori. The study, published in The New England Journal of Medicine, could contribute to the development of tailored genomic medicine for treating stomach cancer.

Stomach cancer is the fourth leading cause of cancer death worldwide and has both environmental and genetic risk factors. Environmentally, infection by H. pylori increases the risk of stomach cancer. Because the virulence of H. pylori in East Asia is high, the incidence of stomach cancer is higher in countries like Japan. Genetically, while hereditary gene variation is why we have different colored eyes and are unique as individuals, sometimes gene variants are associated with the risk of disease. For example, individuals who carry a certain hereditary pathogenic variant of the CDH1 gene have an increased risk of gastric cancer.

Testing for the presence of pathogenic variants is now one of several measures being taken for cancer prevention, surveillance, and treatment selection. However, because large-scale, case-control studies are lacking, and because those that exist have not assessed how the risk for stomach cancer changes when pathogenic variants interact with environmental factors like H. pylori, it remains unclear what actual clinical measures can be taken. To address this issue, researchers therefore evaluated the risk of gastric cancer in a large case-control study of Japanese people, considering whether they were carriers of pathogenic variants and whether they had been infected by H. pylori.

Altered dystrophin expression was found in some tumors and recent studies identified a developmental onset of Duchenne muscular dystrophy (DMD). Given that embryogenesis and carcinogenesis share many mechanisms, we analyzed a broad spectrum of tumors to establish whether dystrophin alteration evokes related outcomes. Transcriptomic, proteomic, and mutation datasets from fifty tumor tissues and matching controls (10,894 samples) and 140 corresponding tumor cell lines were analyzed. Interestingly, dystrophin transcripts and protein expression were found widespread across healthy tissues and at housekeeping gene levels. In 80% of tumors, DMD expression was reduced due to transcriptional downregulation and not somatic mutations. The full-length transcript encoding Dp427 was decreased in 68% of tumors, while Dp71 variants showed variability of expression.

Do you really want to live forever? Futurist Ray Kurzweil has predicted that humans will achieve immortality in just seven years. Genetic engineering company touts ‘Jurassic Park’-like plan to ‘de-extinct’ dodo bird Elon Musk ‘comfortable’ putting Neuralink chip into one of his kids.

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One can only hope.

A former Google engineer has just predicted that humans will achieve immortality in eight years, something more than likely considering that 86% of his 147 predictions have been correct.

Ray Kurzweil visited the YouTube channel Adagio, in a discussion on the expansion of genetics, nanotechnology and robotics, which he believes will lead to age-reversing ‘nanobots’.

Continue reading “Former Google engineer predicts humans will achieve immortality within eight years” »

The actor Bruce Willis was diagnosed with aphasia in April 2022—updated in February 2023 to frontotemporal dementia (FTD). Now, a major advancement is helping develop new treatments for some people with motor neuron diseases, including FTD and ALS, possibly including a nasal spray that could help prevent the genetic disease.

A recently patented genome editing tool called PASTE holds genuine promise for expanding the universe of treatable genetic diseases. The approach combines elements of CRISPR and prime editing with a pair of enzymes designed to enable the integration of large segments of DNA without incurring double-stranded DNA breaks.

U.S. Patent No. 11,572,556, assigned to MIT, covers systems, methods, and compositions for programmable addition via site-specific targeting elements (PASTE). The patent describes site-specific integration of a nucleic acid into a genome, using a CRISPR–Cas9 nickase fused to a reverse transcriptase (RT) and a serine integrase. These enzymes target specific genome sequences known as attachment sites, binding to them before integrating their DNA payload.

PASTE can insert DNA fragments as large as 50,000 base pairs, which puts it on a different plane compared to other genome editing tools such as prime editing.

A new CRISPR tool corrected a genetic mutation that causes vision loss, in an experiment in mice — and its creators at the Wuhan University of Science and Technology (WUST) in China think it could be a safe way to treat countless other genetic diseases in people.

The challenge: Vision starts with light entering the eye and traveling to the retina. There, light-sensitive cells, called photoreceptors, convert light into electrical signals that are sent to the brain.

Retinitis pigmentosa is a rare — and, currently, incurable — genetic disease that can be caused by mutations in more than 100 different genes. These mutations destroy the cells of the retina, leading to vision loss, and for most people, there’s no way to stop the disease or reverse its damage (the exception is a gene therapy approved to treat mutations in the RPE65 gene).