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Category: genetics – Page 324

Fair to say that we all assume that aging is inevitable. In reality however, there is no biological law that says we must age. Over the years we’ve seen a variety of theories proposed to explain why we age including the accumulation of damage to our DNA, the damaging effects of chemicals called “free radicals, changes in the function of our mitochondria, and so many others.

Our guest today, Dr. David Sinclair, believes that aging is related to a breakdown of information. Specifically, he describes how, with time, our epigenome accumulates changes that have powerful downstream effects on the way our DNA functions. Reducing these changes to the epigenome is achievable and in fact, even taking it further, his research now reveals that the epigenome can be reprogrammed back to a youthful state.

David A. Sinclair, PhD, AO is Professor of Genetics at Harvard Medical School, and is the author of Lifespan — Why We Age and Why We Don’t Have To. He is the Founding Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging at Harvard. One of the leading innovators of his generation, he is listed by TIME magazine as one of the “100 most influential people in the world” (2014) and top 50 most important people in healthcare (2018). He is a board member of the American Federation for Aging Research, a Founding Editor of the journal Aging, and has received more than 35 awards for his research on resveratrol, NAD, and reprogramming to reverse aging, which have been widely hailed as major scientific breakthroughs and are topics we discuss in our time together.

In 2018, Dr. Sinclair became an Officer of the Order of Australia, the equivalent of a knighthood, for his work on national security matters and human longevity. Dr. Sinclair and his work have been featured on 60 Minutes, Today, The Wall Street Journal, The New York Times, Fortune, and Newsweek, among others.

In closing, I really need to say that Lifespan (https://amzn.to/3sSoCNS) ranks as one of the most influential books I have ever read. Please enjoy today’s interview.

To stay current on Dr. Sinclair, follow him on Twitter (https://twitter.com/davidasinclair) and Instagram (https://www.instagram.com/davidsinclairphd/)

Continue reading “The Empowering Neurologist — David Perlmutter M.D., and Dr. David Sinclair” | >

Whereas cellular senescence is known to promote aging, many of the mechanisms controlling this process remain poorly understood. Using human mesenchymal precursor cells (hMPCs) carrying pathogenic mutations of the premature aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome, the authors conducted a genome-wide CRISPR-Cas9–based screen to identify genes that could affect cellular senescence. They identified KAT7, a histone acetyltransferase gene, as a driver of senescence. Inactivation of Kat7 in mice aging normally and in prematurely aging progeroid mice extended their life span. Although KAT7 requires further study in other cell types, these experiments highlight the utility of genome-wide CRISPR-Cas9 screens and shed further light on mechanisms controlling senescence.

Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. We performed genome-wide CRISPR-Cas9–based screens using two types of human mesenchymal precursor cells (hMPCs) exhibiting accelerated senescence. The hMPCs were derived from human embryonic stem cells carrying the pathogenic mutations that cause the accelerated aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome. Genes whose deficiency alleviated cellular senescence were identified, including KAT7, a histone acetyltransferase, which ranked as a top hit in both progeroid hMPC models. Inactivation of KAT7 decreased histone H3 lysine 14 acetylation, repressed p15INK4b transcription, and alleviated hMPC senescence.

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Numerous natural products are awaiting discovery in all kinds of natural habitats. Especially microorganisms such as bacteria or fungi are able to produce diverse natural products with high biomedical application potential in particular as antibiotics and anticancer agents. This includes the so-called red yeast of the species Rhodotorula mucilaginosa, isolated from a deep-sea sediment sample from the Mid-Atlantic Ridge and analyzed for its genome and chemical constituents by researchers from GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech) of GEOMAR Helmholtz Centre for Ocean Research Kiel and Kiel University (CAU). In a joint effort, the scientists succeeded in demonstrating its anticancer and antibacterial effects. This study, partly-funded by Kiel Marine Science (KMS) of Kiel University, was recently published in the renowned scientific journal Marine Drugs.

A unique opportunity arose for researchers in the Department of Botanical Genetics and Molecular Biology at Kiel University, headed by Professor Frank Kempken. Via the Institute of Geosciences at Kiel University, his group had access to sediment samples from the Mid-Atlantic Ridge in 1600—4000 m depth collected during a research cruise with the German research vessel MARIA S. MERIAN. From one of these sediment cores taken at a depth of 3600 m, Prof. Kempken´s group succeeded in isolating and cultivating living fungi of the species Rhodotorula mucilaginosa. This slowly growing type of yeast, which belongs to the so-called Basidiomycete yeasts should not be confused with the well-known baker’s yeast. The species originally grows at great depth tolerating high hydrostatic pressure and rather cold temperatures.

“With the applied methodology we have succeeded in cultivating yeast colonies that can withstand and grow at room temperatures and under atmospheric pressure. These experiments have shown once more that microorganisms with specific physiological properties thrive in distinct ecological niches. The experiments have shown us further that special ecological niches can produce microorganisms with special characteristics. The assumption about the adaptability of this special genus has therefore encouraged us to further analyze this species,” says Kempken, whose research group has been analyzing genomes of marine fungi for more than ten years.

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The ancient Egyptians mummified an abundance of cats during the Late Period (664 — 332 BC). The overlapping morphology and sizes of developing wildcats and domestic cats confounds the identity of mummified cat species. Genetic analyses should support mummy identification and was conducted on two long bones and a mandible of three cats that were mummified by the ancient Egyptians. The mummy DNA was extracted in a dedicated ancient DNA laboratory at the University of California – Davis, then directly sequencing between 246 and 402 bp of the mtDNA control region from each bone. When compared to a dataset of wildcats (Felis silvestris silvestris, F. s. tristrami, and F. chaus) as well as a previously published worldwide dataset of modern domestic cat samples, including Egypt, the DNA evidence suggests the three mummies represent common contemporary domestic cat mitotypes prevalent in modern Egypt and the Middle East. Divergence estimates date the origin of the mummies’ mitotypes to between two and 7.5 thousand years prior to their mummification, likely prior to or during Egyptian Predyanstic and Early Dynastic Periods. These data are the first genetic evidence supporting that the ancient Egyptians used domesticated cats, F. s. catus, for votive mummies, and likely implies cats were domesticated prior to extensive mummification of cats.

Keywords: ancient DNA, Felis silvestris catus, mitochondrial, control region, domestication.

Ancient Egyptian culture is well known for its reverence and mummification of cats (Ginsburg, et al., 1991). Cats featured in early Egyptian art and skeletal remains from c. 4000 BC, has led scholars to conclude that our current feline companions might have been domesticated in Egypt (Baldwin, 1975, Ginsburg, et al., 1991, Linseele, et al., 2007). However, the first documentation of wildcat taming, the precursor to domestication, is an archeological finding in Cyprus of a potential wildcat buried with a human, dating to approximately 9500 years ago (Vigne, et al., 2004), implying prior to the Predynastic Period in Egypt. Recent genetic studies have suggested that the origins of cat domestication occurred in the adjacent Near Eastern sites (Driscoll, et al., 2007, Lipinski, et al., 2008) as domestic cats have derived mitotypes from regional wildcats and the genetic diversity of modern domestic cats is highest within these regions.

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Weird, right?

The team’s critical insight was to construct a “viral language” of sorts, based purely on its genetic sequences. This language, if given sufficient examples, can then be analyzed using NLP techniques to predict how changes to its genome alter its interaction with our immune system. That is, using artificial language techniques, it may be possible to hunt down key areas in a viral genome that, when mutated, allow it to escape roaming antibodies.

It’s a seriously kooky idea. Yet when tested on some of our greatest viral foes, like influenza (the seasonal flu), HIV, and SARS-CoV-2, the algorithm was able to discern critical mutations that “transform” each virus just enough to escape the grasp of our immune surveillance system.

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No that’s not clickbait.
Being able to stop and reverse aging is probably something every single person has yearned for at some point in their life. Now researchers are finally seeing successful implementations of methods for reversing aging in Animal cells. This creates the potential for countless benefits for humans. These range from simply preventing age related illness all the way to allowing women the opportunity to have kids at any point in their life when they are ready. We are living in very exciting scientific times.

References:

Reprogramming to recover youthful epigenetic information and restore vision — https://doi.org/10.1038/s41586-020-2975-4

NAD+ Repletion Rescues Female Fertility during Reproductive Aging — https://doi.org/10.1016/j.celrep.2020.01.

Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16 — https://doi.org/10.1007/s10522-009-9225-3

Age-related NAD+ decline — https://doi.org/10.1016/j.exger.2020.

Continue reading “We Can Reverse Aging” | >

Researchers from Tokyo Metropolitan University have discovered that fruit flies with genetic modifications to enhance glucose uptake have significantly longer lifespans. Looking at the brain cells of aging flies, they found that better glucose uptake compensates for age-related deterioration in motor functions, and led to longer life. The effect was more pronounced when coupled with dietary restrictions. This suggests healthier eating plus improved glucose uptake in the brain might lead to enhanced lifespans.

The brain is a particularly power-hungry part of our bodies, consuming 20% of the oxygen we take in and 25% of the glucose. That’s why it’s so important that it can stay powered, using the glucose to produce (ATP), the “energy courier” of the body. This , known as glycolysis, happens in both the intracellular fluid and a part of cells known as the mitochondria. But as we get older, our become less adept at making ATP, something that broadly correlates with less glucose availability. That might suggest that more food for more glucose might actually be a good thing. On the other hand, it is known that a healthier diet actually leads to longer life. Unraveling the mystery surrounding these two contradictory pieces of knowledge might lead to a better understanding of healthier, longer lifespans.

A team led by Associate Professor Kanae Ando studied this problem using Drosophila . Firstly, they confirmed that brain cells in older flies tended to have lower levels of ATP, and lower uptake of glucose. They specifically tied this down to lower amounts of the enzymes needed for glycolysis. To counteract this effect, they genetically modified flies to produce more of a glucose-transporting protein called hGut3. Amazingly, this increase in glucose uptake was all that was required to significantly improve the amount of ATP in cells. More specifically, they found that more hGut3 led to less decrease in the production of the enzymes, counteracting the decline with age. Though this did not lead to an improvement in age-related damage to mitochondria, they also suffered less deterioration in locomotor functions.

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Important here is at 38:13 where he says not only is his TAME trial paid for but an organization is going to pay a billion dollars per year on aging. He was not allowed to give details but it was going to start this month. I’ll be watching for the news.

Zoom Transcription: https://otter.ai/u/vTb6HEbcyTXBPgVrgRzB3I0CDC8

Dr. Nir Barzilai discusses the TAME Trial and what this group may learn from the successes for advancing progress on biomarkers in particular and on aging in general.

About Nir Barzilai:

Nir Barzilai, MD, is a Professor in the Department of Endocrinology Medicine and the Department of Genetics at the Albert Einstein College of Medicine. He is also the Ingeborg and Ira Leon Rennert Chair of Aging Research at the Albert Einstein College of Medicine.

Continue reading “TAME & Biomarker Q&A with Nir Barzilai, Institute for Aging Research” | >