Lifeboat Foundation

Circa 2020 Immortality of the heart and heart regeneration.

Cardiovascular diseases represent the major cause of morbidity and mortality worldwide. Multiple studies have been conducted so far in order to develop treatments able to prevent the progression of these pathologies. Despite progress made in the last decade, current therapies are still hampered by poor translation into actual clinical applications. The major drawback of such strategies is represented by the limited regenerative capacity of the cardiac tissue. Indeed, after an ischaemic insult, the formation of fibrotic scar takes place, interfering with mechanical and electrical functions of the heart. Hence, the ability of the heart to recover after ischaemic injury depends on several molecular and cellular pathways, and the imbalance between them results into adverse remodeling, culminating in heart failure. In this complex scenario, a new chapter of regenerative medicine has been opened over the past 20 years with the discovery of induced pluripotent stem cells (iPSCs). These cells share the same characteristic of embryonic stem cells (ESCs), but are generated from patient-specific somatic cells, overcoming the ethical limitations related to ESC use and providing an autologous source of human cells. Similarly to ESCs, iPSCs are able to efficiently differentiate into cardiomyocytes (CMs), and thus hold a real regenerative potential for future clinical applications. However, cell-based therapies are subjected to poor grafting and may cause adverse effects in the failing heart. Thus, over the last years, bioengineering technologies focused their attention on the improvement of both survival and functionality of iPSC-derived CMs. The combination of these two fields of study has burst the development of cell-based three-dimensional (3D) structures and organoids which mimic, more realistically, the in vivo cell behavior. Toward the same path, the possibility to directly induce conversion of fibroblasts into CMs has recently emerged as a promising area for in situ cardiac regeneration. In this review we provide an up-to-date overview of the latest advancements in the application of pluripotent stem cells and tissue-engineering for therapeutically relevant cardiac regenerative approaches, aiming to highlight outcomes, limitations and future perspectives for their clinical translation.

Cardiovascular diseases represent the major cause of morbidity and mortality worldwide, accounting for 31% of all deaths (Organization WH 2016). Myocardial infarction (MI) is associated with necrosis of the cardiac tissue due to the occlusion of the coronary arteries, a condition that irrevocably diminishes oxygen and nutrient delivery to the heart (Thygesen et al., 2007). While effective therapies, including surgical approaches, are currently used to treat numerous cardiac disorders, such as valvular or artery diseases, available therapeutic treatments for the damaged myocardium are still very limited and poorly effective. Furthermore, after an ischaemic insult, the formation of fibrotic scar takes place, interfering with mechanical and electrical functions of the cardiac tissue (Talman and Ruskoaho, 2016).

Mitochondrial uncoupling by agents such as BAM15 may mitigate age-related decline in muscle mass and function by molecular and cellular bioenergetic adaptations that confer protection against sarcopenic obesity.

Background Sarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified that a mitochondrial-targeted furazano[3,4-b]pyrazine named BAM15 is orally available and selectively lowers respiratory coupling efficiency and protects against diet-induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity.

Circa 2018 immortality of the kidneys.

Kidney regeneration from pluripotent stem cells is receiving a lot of attention because limited treatments are currently available for chronic kidney disease (CKD). It has been shown that uremic state in CKD is toxic to somatic stem/progenitor cells, such as endothelial progenitor and mesenchymal stem cells, affecting their differentiation and angiogenic potential. Recent studies reported that specific abnormalities caused by the non-inherited disease are often retained in induced pluripotent stem cell (iPSC)-derived products obtained from patients. Thus, it is indispensable to first assess whether iPSCs derived from patients with CKD due to non-inherited disease (CKD-iPSCs) have the ability to generate kidneys.

Circa 2021 First breakthrough in immortality of the eyes of rats using the inducing of pluripotent stem cells in the eye. Which will eventually lead to immortality of the human eye.

The retina is neural tissue located in the posterior part of the eye and is an extension of the central nervous system (CNS), which has limited regenerative potential once damaged¹. Therefore, to maintain homeostasis of the retinal microenvironment and protect itself from harmful stimuli, the retina has a unique structure consisting of inner and outer blood-retinal barriers (BRBs)^2,3,4. The outer BRB is mainly composed of retinal pigment epithelial (RPE) cells, which support photoreceptor cells, the primary neurons in the retina, and play a significant role in the pathogenesis of retinal degenerative disorders, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP)^5,6,7,8,9. These disorders are commonly characterized by the irreversible loss of photoreceptor cells and RPE cells, and the only fundamental treatment for these retinal degenerative disorders is replacement of damaged or atrophied cells^10,11,12. Thus, regenerative treatments, such as stem cell transplantation, are emerging as attractive options for targeting retinal degeneration that was previously considered untreatable¹³.

RP refers to a set of hereditary retinal degenerative disorders that initially involve photoreceptors and leads to subsequent RPE cell damage; it affects 1 in 4,000 individuals worldwide⁹. Due to its inherent nature, extensive genetic studies are ongoing, and more than 50 causal genes have been identified¹⁴. Among the causal genes, PDE6B is a gene that encodes rod cGMP-phosphodiesterase, which is a critical component of the biochemical light transduction pathway⁹. Although various molecular and genetic studies have identified the pathomechanisms of RP, attempts to restore vision in patients with RP have failed. To overcome this issue, preclinical stem cell-based studies involving transient dosing or permanent implantation of pluripotent stem cells are being conducted^10,11,15,16.

Continue reading “Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats” »

Materials scientists and bioengineers at the intersection of regenerative medicine and bioinspired materials seek to develop shape-programmable artificial muscles with self-sensing capabilities for applications in medicine. In a new report now published in Science Advances, Haoran Liu and a team of researchers in systems and communications engineering at the Frontier Institute of Science and Technology, Jiaotong University, China, were inspired by the coupled behavior of muscles, bones, and nerve systems of mammals and other living organisms to create a multifunctional artificial muscle in the lab. The construct contained polydopamine-coated liquid crystal elastomer (LCE) and low-melting point alloys (LMPA) in a concentric tube or rod. While the team adopted the outer liquid crystal-elastomer to mimic reversible contraction and recovery, they implemented the inner low-melting point alloy for deformation locking and to detect resistance mechanics, much like bone and nerve functions, respectively. The artificial muscle demonstrated a range of performances, including regulated bending and deformation to support heavy objects, and is a direct and effective approach to the design of biomimetic soft devices.

Soft robotics inspired by the skeleton–muscle–nerve system

Scientists aim to implement biocompatibility between soft robotic elements and human beings for assisted movement and high load-bearing capacity; however, such efforts are challenging. Most traditional robots are still in use in industrial, agricultural and aerospace settings for high-precision sensor-based, load-bearing applications. Several functional soft robots contrastingly depend on materials to improve the security of human-machine interactions. Soft robots are therefore complementary to hard robots and have tremendous potential for applications. Biomimetic constructs have also provided alternative inspiration to emulate the skeleton-muscle-nerve system to facilitate agile movement and quick reaction or thinking, with a unique body shape to fit tasks and perform diverse physiological functions. In this work, Liu et al were inspired by the fascinating idea of biomimicry to develop multifunctional artificial muscles for smart applications.

‘Barcoding’ studies discovered two independent sources for blood cells in mice. If confirmed in humans, our understanding of blood cancers, bone marrow transplants, and the aging immune system will change.

The origins of our blood may not be quite what we thought. Using cellular “barcoding” in mice, groundbreaking research finds that blood cells originate not from one type of mother cell, but two, with potential implications for blood cancers, bone marrow transplant, and immunology. Fernando Camargo, PhD, of the Stem Cell Program at Boston Children’s Hospital led the study, published in the journal Nature on June 15, 2022.

“Historically, people have believed that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells,” says Camargo, who is also a member of the Harvard Stem Cell Institute and a professor at Harvard University. “We were surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing.”

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Continue reading “Bill Faloon presents a classic Age Reversal Update” »

Just a quick update in the E5 experiment all control rats have died and 3 treated rats remain.

Does the survival curve reflect the epigenetic age reduction seen in previous experiment? Blog post from the Live Forever Club.

Continue reading “Harold Katcher’s E5/Elixir (Young Plasma) Rat Trial Results” »

Human Longevity Inc, which was built by the pioneers of the human genome sequencing effort, and Freedom Acquisition Corporation, a publicly traded special purpose acquisition company (SPAC), have announced that they have signed a non-binding letter of intent for a proposed business combination that would result in HLI becoming a publicly listed company. Assuming everything ticks along as planned, the parties currently expect to seek approval from Freedom’s shareholders by the first quarter of 2023.

Longevity. Technology: Unicorns are the stuff of legends and headlines, and while there can be no assurance that a definitive agreement will be entered into or that the proposed transaction will be consummated, the speculation is delicious because longevity start-ups with billion-dollar valuations mean more visible, accelerating progress for the sector.

The proposed transaction values the combined company at approximately $1 billion, providing HLI with funding to pursue growth and technology innovation – watch this space!