Lifeboat Foundation

One of the hallmarks of aging, cellular senescence is what happens when aging cells do not die in the usual way (a process known as apoptosis) and start to accumulate in our bodies. The accumulation of these “senescent” cells is implicated in diseases including dementias, atherosclerosis, cancers, diabetes and arthritis. But senescence is not just part of the aging process – it tends to occur in individuals who develop frailty and multiple illnesses, and this can occur at any point during life.

In 2015, a team of researchers at the Mayo Clinic, led by Dr James L Kirkland, published a seminal paper in Aging Cell that introduced a new class of drugs called senolytics. Based on the idea that removing senescent cells may enhance human healthspan, these drugs were identified based on their ability to selectively target and eliminate those cells.

Longevity. Technology: Since the discovery of the first senolytics, hundreds of others have since been identified or created, and senotherapeutics is now one of the hottest areas in longevity, with a host of clinical trials under way and companies pursuing senolytic therapies for a range of age-related conditions. But what does the man who started it all think about the therapeutic field he helped create? In the first of two articles, we bring you Dr Kirkland’s unique perspective on the world of senolytics.

New research from the University of Cincinnati bolsters a hypothesis that Alzheimer’s disease is caused by a decline in levels of a specific protein, contrary to a prevailing theory that has been recently called into question.

UC researchers led by Alberto Espay, MD, and Andrea Sturchio, MD, in collaboration with the Karolinska Institute in Sweden, published the research on Oct. 4 in the Journal of Alzheimer’s Disease.

The research is focused on a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, meaning dissolvable in water, but it sometimes hardens into clumps, known as amyloid plaques.

A new theory of consciousness (that is, how we perceive ourselves and the world around us) has been proposed, in which our brains aren’t actually actively…

Summary: A newly discovered second stem cell population in the mouse brain is responsible for the production of new neurons in the olfactory bulb of adult mice.

Source: Heidelburg University.

In the brain of adult mammals, neural stem cells ensure that new nerve cells, i.e. neurons, are constantly formed. This process, known as adult neurogenesis, helps mice maintain their sense of smell.

Summary: Boosting omega-3 fatty acid intake helps to preserve brain health and improve cognition in middle age, a new study reports. For those with the Alzheimer’s associated APOE4 gene, omega-3 fatty acid intake was associated with greater hippocampal volume and less small vessel disease.

Source: UT San Antonio.

Eating cold-water fish and other sources of omega-3 fatty acids may preserve brain health and enhance cognition in middle age, new evidence indicates.

A multidisciplinary team from two Johns Hopkins University institutions, including neurotoxicologists and virologists from the Bloomberg School of Public Health and infectious disease specialists from the school of medicine, has found that organoids (tiny tissue cultures made from human cells that simulate whole organs) known as “mini-brains” can be infected by the SARS-CoV-2 virus that causes COVID-19.

The results, which suggest that the virus can infect human brain cells, were published online June 26, 2020, in the journal ALTEX: Alternatives to Animal Experimentation.

Early reports from Wuhan, China, the origin of the COVID-19 pandemic, have suggested that 36% of patients with the disease show neurological symptoms, but it has been unclear whether or not the virus infects human brain cells. In their study, the Johns Hopkins researchers demonstrated that certain human neurons express a receptor, ACE2, which is the same one that the SARS-CoV-2 virus uses to enter the lungs. Therefore, they surmised, ACE2 also might provide access to the brain.

This could help us understand diseases better.

Researchers at the University of Utah have developed seed-sized brain organoids that can not only organize themselves but also provide us insights into the causes of autism, a press release said.

Organoids, tiny clusters of tissue derived from stem cells, allow researchers to replicate the complex organs outside the body while also controlling conditions around them… More.

Continue reading “US researchers grow brain organoids in a lab, just like they would develop in the fetus” »

Accurate detection and manipulation of endogenous proteins is essential to understand cell biological processes, which motivated laboratories across cell biology to develop highly efficient CRISPR genome editing methods for endogenous epitope tagging (Auer et al., 2014; Nakade et al., 2014; Lackner et al., 2015; Schmid-Burgk et al., 2016; Suzuki et al., 2016; Nishiyama et al., 2017; Artegiani et al., 2020; Danner et al., 2021). Multiplex editing using NHEJ-based CRISPR/Cas9 methods remains limited because of the high degree of cross talk that occurs between two knock-in loci (Gao et al., 2019; Willems et al., 2020). In the current study we present CAKE, a mechanism to diminish cross talk between NHEJ-based CRISPR/Cas9 knock-ins using sequential activation of gRNA expression. We demonstrate that this mechanism strongly reduces cross talk between knock-in loci, and results in dual knock-ins for a wide variety of genes. Finally, we showed that CAKE can be directly applied to reveal new biological insights. CAKE allowed us to perform two-color super-resolution microscopy and acute manipulation of the dynamics of endogenous proteins in neurons, together revealing new insights in the nanoscale organization of synaptic proteins.

The CAKE mechanism presented here creates a mosaic of Cre_ON and Cre_OFF knock-ins, and the number of double knock-in cells depends on the efficacy of each knock-in vector. Therefore, to obtain a high number of double knock-in cells, the efficacy of both the Cre_ON and Cre_OFF knock-in vector must be optimized. We identified three parameters that regulate the efficacy for single and double knock-ins in neurons. First, the efficacy of gRNAs varies widely, and even gRNAs that target sequences a few base pairs apart in the same locus can have dramatically different knock-in rates (Willems et al., 2020; Danner et al., 2021; Fang et al., 2021; Zhong et al., 2021). Thus, the efficacy of each individual gRNA must be optimized to increase the chance of successful multiplex labeling in neurons. gRNA performance is dependent on many factors, including the rate of DNA cleavage and repair (Rose et al., 2017; Liu et al., 2020; Park et al.

Carnegie Mellon University researchers have pioneered the CMU Array—a new type of microelectrode array for brain computer interface platforms. It holds the potential to transform how doctors are able to treat neurological disorders.

The ultra-high-density microelectrode array (MEA), which is 3D-printed at the nanoscale, is fully customizable. This means that one day, patients suffering from epilepsy or limb function loss due to stroke could have personalized medical treatment optimized for their individual needs.

Continue reading “Researchers pioneer nanoprinting electrodes for customized treatments of neurological disorders” »