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Archive for the ‘biotech/medical’ category: Page 1651

Feb 27, 2020

Induction of anti-aging gene klotho with a small chemical compound that demethylates CpG islands

Posted by in categories: biotech/medical, genetics, life extension

Klotho (KL) is described as an anti-aging gene because mutation of Kl gene leads to multiple pre-mature aging phenotypes and shortens lifespan in mice. Growing evidence suggests that an increase in KL expression may be beneficial for age-related diseases such as arteriosclerosis and diabetes. It remains largely unknown, however, how Kl expression could be induced. Here we discovered novel molecular mechanism for induction of Kl expression with a small molecule ‘Compound H’, N-(2-chlorophenyl)-1 H-indole-3-caboxamide. Compound H was originally identified through a high-throughput screening of small molecules for identifying Kl inducers. However, how Compound H induces Kl expression has never been investigated. We found that Compound H increased Kl expression via demethylation in CpG islands of the Kl gene. The demethylation was accomplished by activating demethylases rather than inhibiting methylases. Due to demethylation, Compound H enhanced binding of transcription factors, Pax4 and Kid3, to the promoter of the Kl gene. Pax4 and Kid3 regulated Kl promoter activity positively and negatively, respectively. Thus, our results show that demethylation is an important molecular mechanism that mediates Compound H-induced Kl expression. Further investigation is warranted to determine whether Compound H demethylates the Kl gene in vivo and whether it can serve as a therapeutic agent for repressing or delaying the onset of age-related diseases.

Keywords: klotho, methylation, Pax4, Kid3, CpG island.

Pre-mature aging phenotypes were eminent in the klotho (Kl)-deficient mice, which have ~ 10 copies of a transgene integrated in the 5’ flanking region of the Kl gene disrupting its expression [1]. The klotho mice die around ~ 2 months of age after birth due to multiple aging-related organ failures [1]. Later, the role of KL in aging was confirmed by the reproduction of the same aging phenotypes in Kl knockout homozygous (Kl −/−) mice [2]. On the other hand, overexpression of KL extends lifespan by 20–30% [2, 3]. The protein products of Kl gene can be divided into two forms: membrane-integrated form of Kl and non-integrated form of Kl which includes secreted and soluble Kl (sKl). These two type of proteins are produced from the two transcripts that arise from a single kl gene due to alternative RNA splicing [4, 5].

Feb 27, 2020

11 Best Foods to Boost Your Brain and Memory

Posted by in categories: biotech/medical, health, neuroscience

You can improve your brain health with the right diet. Eat these 11 foods to boost your memory and focus, help prevent disease and keep sharp as you age.

Feb 27, 2020

The anti-aging protein Klotho is induced by GABA therapy and exerts protective and stimulatory effects on pancreatic beta cells

Posted by in categories: biotech/medical, life extension, neuroscience

Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes. Here, we report that GABA markedly increased circulating levels of Klotho in streptozotocin (STZ)-induced diabetes. GABA also increased Klotho in the islet of Langerhans of normal mice, as well as the islets and kidneys of STZ-treated mice. In vitro, GABA stimulated production and secretion of Klotho by human islet cells. Knockdown (KD) of Klotho with siRNA in INS-1E insulinoma cells abrogated the protective effects of GABA against STZ toxicity. Following KD, soluble Klotho reversed the effects of Klotho deficiency. In human islet cells soluble Klotho protected against cell death, and stimulated proliferation and insulin secretion. NF-κB activation triggers beta-cell apoptosis, and both GABA and Klotho suppress this pathway. We found Klotho KD augmented NF-κB p65 expression, and abrogated the ability of GABA to block NF-κB activation. This is the first report that GABAergic stimulation increases Klotho expression. Klotho protected and stimulated beta cells and lack of Klotho (KD) was reversed by soluble Klotho. These findings have important implications for the treatment of T1D.

Feb 27, 2020

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

Posted by in categories: biotech/medical, evolution, food, life extension, neuroscience

Circa 2017


Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

Keywords: Meat, nicotinamide, evolution, NAD(H), vitamin B3, Malthus, fertility, immunological tolerance, longevity.

Continue reading “Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics” »

Feb 27, 2020

With an Eye to Human Life Extension, Researchers Try to Slow Aging in Dogs

Posted by in categories: biotech/medical, life extension

A drug that helps people after organ transplants has extended the lives of fruit flies, worms, and mice. The next step is to see what it will do for our pets.

Feb 27, 2020

FDA-Approved HIV Medicines

Posted by in category: biotech/medical

Fact sheets about HIV/AIDS treatment information, the prevention of mother-to-child transmission, and HIV treatment side effects. All the fact sheets are written specifically for patients in easy to read language.

Feb 27, 2020

How the New Coronavirus Spreads and Progresses – And Why One Test May Not Be Enough

Posted by in category: biotech/medical

A novel coronavirus that first appeared in Wuhan, China, in December continues to sicken tens of thousands of people around the world – and scientists are working round the clock to better understand the virus, contain the outbreak, and treat the disease.

In the weeks since the outbreak, the disease has been named COVID-19 by the World Health Organization. (The virus itself has been named SARS-CoV-2 by the International Committee on Taxonomy of Viruses).

UC San Francisco infectious disease expert Charles Chiu, MD, PhD, has been following the disease since its outbreak and provided the latest updates on what science has revealed about how the coronavirus is transmitted, what happens to someone who’s infected, and why a single diagnostic test may not be enough.

Feb 27, 2020

Wearable chair

Posted by in categories: biotech/medical, wearables

This wearable chair will help doctors through long surgeries.

Feb 27, 2020

Pope Francis, 83, cancels event as he’s taken ill amid Italy coronavirus crisis

Posted by in category: biotech/medical

POPE Francis cancelled a church service today after he was struck down with illness.

The 83-year-year-old pontiff was not well enough to attend the mass, although there is no suggestion at this stage he has coronavirus as the outbreak in Italy topped 500 cases.

The Pope covered his mouth as he coughed.

Feb 27, 2020

Trump says coronavirus will ‘disappear’ eventually

Posted by in category: biotech/medical

Wuhan coronavirus pandemic — US strategic response.

“It’s going to disappear. One day it’s like a miracle, it will disappear,” said Trump.

🤣🤣🤣

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