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Category: life extension – Page 406

Scientists create first roadmap of human skeletal muscle development

An interdisciplinary team of researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA has developed a first-of-its-kind roadmap of how human skeletal muscle develops, including the formation of muscle stem cells.

The study, published in the peer-reviewed journal Cell Stem Cell, identified various cell types present in skeletal muscle tissues, from all the way to adulthood. Focusing on muscle progenitor cells, which contribute to muscle formation before birth, and muscle stem cells, which contribute to muscle formation after birth and to regeneration from injury throughout life, the group mapped out how the cells’ gene networks—which genes are active and inactive—change as the cells mature.

The roadmap is critical for researchers who aim to develop muscle stem cells in the lab that can be used in regenerative cell therapies for devastating muscle diseases, including muscular dystrophies, and sarcopenia, the age-related loss of muscle mass and strength.

Epigenetic changes during aging and their reprogramming potential

If you are interested in age reversal, and you haven’t read Dr David Sinclair (Harvard Medical School) yet, then I’d recommend this research paper.

“Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.”

The aging process results in significant epigenetic changes at all levels of chromatin and DNA organization. These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors. Exactly how and why these changes occur is not fully understood, but evidence that these epigenetic changes affect longevity and may cause aging, is growing. Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.

The term “epigenetics” is thrown around a lot. Originally, it was coined to describe heritable changes that were non-mendelian, but use of the term has evolved. These days, “epigenetics” more generally refers to all non-genomic information storage in cells including gene networks, chromatin structure and post-translational modifications to histones. With aging, there are distinct changes across the epigenome from DNA modifications to alterations in global chromatin organization. But key questions remain unanswered: How and why do these changes occur? Do these changes drive disease and aging? Are they reversible?

Genomic organization is determined by the complex structure of chromatin ( Figure 1 ). The basic unit of chromatin is the nucleosome, which is made up of 147 DNA base pairs wrapped around an octamer of histone proteins. This octamer usually comprises two copies each of H2A, H2B, H3 and H4 (Luger et al. 1997; Hansen 2002). Within nucleosomes, both histones and the DNA itself are subject to a range of chemical modifications that affect the chromatin structure and ultimately the expression of genes. Chromatin falls into one of two major subtypes: euchromatin, in which the chromatin is open and transcriptionally active and heterochromatin, in which the chromatin is tightly closed and transcriptionally silent (Wallrath 1998; Grewal and Moazed 2003). Regulating the epigenetic network are factors that modify chromatin including DNA- and histone-modifying enzymes, transcription factors, and the more recently identified noncoding RNAs (ncRNAs).

Neuroplasticity In Action

Neuroplasticity is the brain’s ability to change under the influence of experience and activities. Several aspects of neuroplasticity are noteworthy: neurogenesis (development of new nerve cells) and synaptogenesis (development of new contacts between nerve cells) among them. Neuroplasticity used to be thought of as a limited phenomenon, mostly restricted to the early years of life. More recently it has been demonstrated that neuroplasticity continues throughout life, even in advanced age. This provides the conceptual basis for a wide range of therapeutic efforts aiming to slow the detrimental effects of aging on the brain and to treat various brain disorders.

What are the factors influencing neuroplasticity? The question is compelling both as a scientific challenge and because of the therapeutic promise of neuroplasticity once we know how to control and harness it. Among such factors, the environmental factors influencing neuroplasticity are particularly intriguing. It turns out that a strong relationship exists between what people do with their brains and how their brains age.

Both anecdotal observations and formal research suggest that education confers a protective effect against dementia. Highly educated people are less likely to succumb to its effects. Robert Katzman was the first to note that the prevalence of dementia, including Alzheimer’s disease, is lower in people with advanced education. The MacArthur Foundation Research Network on Successful Aging sponsored a study of the predictors of cognitive change in older persons. Education emerged as by far the most powerful predictor of cognitive vigor in old age.

Blood Factors Reverse Epigenetic Age

Crucially, plasma treatment of the old rats reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats. According to the six epigenetic clocks, the plasma fraction treatment rejuvenated liver by 73.4%, blood by 52%, heart by 52%, and hypothalamus by 11%. The rejuvenation effects are even more pronounced if we use the final versions of our epigenetic clocks: liver 75%, blood 66%, heart 57%, hypothalamus 19%. According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%.

Researchers have demonstrated that epigenetic age can be halved in rats by using signals commonly found in the blood.

Epigenetic changes

One of the proposed reasons we age are the changes to gene expression that our cells experience as we get older; these are commonly called epigenetic alterations. These alterations harm the fundamental functions of our cells and can increase the risk of cancer and other age-related diseases.

Reversing age: dual species measurement of epigenetic age with a single clock

Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.

Several authors are founders, owners, employees (Harold Katcher and Akshay Sanghavi) or consultants of Nugenics Research (Steve Horvath and Agnivesh Shrivastava) which plans to commercialize the “Elixir” treatment. Other authors (Kavita Singh, Shraddha Khairnar) received financial support from Nugenics Research. The other authors do not have conflict of interest.

You CAN live forever… as long as you are a flatworm, say scientists

Circa 2012

Forget expensive lotions and potions – the key to becoming immortal could be found in flatworms, scientists say.

The worms, which live in lakes and ponds, hold the remarkable ability to regenerate time and time again – effectively living forever.

If one is cut in half, the head portion grows a tail and the tail portion grows a head. Cut it into 20 pieces and 20 new worms, each an exact copy of the first, are created.

Human Induced Pluripotent Stem Cells : Clinical Significance and Applications in Neurologic Diseases

face_with_colon_three could heal body parts in humans.

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson’s disease, Alzheimer’s disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

Stem cells exhibit the capacity of self-renewal and may undergo differentiation into various tissue types. These are divided into pluripotent stem cells (PSCs; embryonic stem cells [ESCs] and induced pluripotent stem cells [iPSCs]) and multipotent stem cells (adult stem cells [ASCs]) based on their differentiation capacity [45]. PSCs, including ESCs derived from embryos and iPSCs derived by gene transfer, may undergo indefinite proliferation and differentiate into different types of tissues depending on the treatment conditions [86]. Multipotent stem cells, however, may be obtained from tissue-derived precursors (umbilical cord blood, bone marrow, adipose tissue, placenta, or blood), which are already grown tissues.

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