Category Archives: David Sinclair

In The Curious Case of Benjamin Button, a boy was born old and got younger. That film is science fiction but Australian scientist Professor David Sinclair, currently at Harvard University Medical School and his colleagues have managed to get yeast and more recently mice to grow younger.

Aging has multiple causes, until recently none have been considered treatable. It is the diseases of old age: dementia, heart disease and osteoporosis that have been treated.

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In a YouTube interview with entrepreneur Tom Bilyeu, Professor Sinclair asks are we treating the symptoms rather than the condition ageing that causes them?

Research has led to lifespans increasing, but older people often spend years in poor health.

Humans have around 20,000 genes. These provide the cell with instructions to make proteins. Not all of them are needed in every cell. Those that arent needed are turned off by process called epigenetics. This ensures genes are not active in inappropriate cell types. For example the COL1A1 gene codes to produce collagen, but only needs to be active in skin, cartilage and similar types of cell.

Sinclairs team believes that the loss of epigenetic information is the root cause of ageing. They have identified drugs that can reset a cells epigenetic status and reverse its age. These drugs can be delivered by a harmless virus to specific tissues or the entire body, thereby causing cells to act younger and wounds to heal faster.

Genes called sirtuins make enzymes that control how cells function and they can be used to turn off genes that hasten ageing.

Sever calorie restriction increases the lifespan of mice and yeast, but thats not really practical for humans.

However, Professor Sinclair says a short period of being hungry or stressed in other ways causes sirtuins to turn on the mechanism that repairs cell damage and resets the biological clock.

Other compounds can activate sirtuins. Resveratol, found in small amounts in red wine, activates sirtuins in mice when fed large doses. Metformin, used to control blood sugar levels in diabetics, acts in the same way. Diabetics who take metformin tend to outlive those who dont.

Next Sinclairs lab looked at the way mitochondria (the cell organelles that generate energy) operate. The levels of nicotinamide adenine dinucleotide (NAD+) in mitochondria dictate how long cell survive, but NAD+ declines with age.

Professor Sinclair and his co-researchers found that restoring NAD+ levels in mammals has a dramatically positive effect on the liver, heart, reproductive organs, kidney, muscles, and brain and nervous systems. Old mice given a NAD+ booster drug ran around like young mice within a few days.

They study the mechanisms by which the NAD+level repairs DNA and look for ways to improve this process. In particular, they study enzymes that deplete or increase NAD+ as potential tools to control the NAD+ level in the cells.

They have also actively looked for sirtuin activating compounds (STACs) and have discovered potent activators that raise NAD+ levels. They are testing these for their effects on ageing and age-related diseases.

But mice are not people, so it is too early to start taking NAD-boosting drugs until the results of human trials are completed.

Sinclairs advice for longevity is to avoid scans and X-rays as much as possible as they damage your DNA and get a little bit hungry from time to time. He spends four hours a week at the gym, include one hour doing yoga and an hour in the sauna.

He says the stress of jumping into cold water after the hot steam room and hot tub increases brown fat in his body. Brown fat has lots of mitochondria which raises the metabolic rate and helps to prevent excessive weight gain.

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There is no reason to accept ageing as inevitable, Harvard professor Dr David Sinclair said on Friday, adding that if a pill or a vaccine is not developed in the next 30 years to fight ageing, something must have gone terribly wrong.

Dr Sinclair, co-director of the Paul F Glenn Center for Biology of Aging Research at Harvard Medical School, and his team recently turned back the clock on aged eye cells in the retina to reverse vision loss in elderly mice.

Ageing is going to happen We are not going to live forever But can we try to live another 5 or 10 or 20 years longer, healthily? Absolutely... There is no law that says that we couldnt live longer, he said at the 18th Hindustan Times Leadership Summit.

Dr Sinclair, best known for his work on understanding why humans age and how to slow its effects, said it was important to declare ageing as a disease so that governments change laws to treat it with medicines and more funds are accessible for scientific work.

If it [a pill or a vaccine to reverse ageing] doesnt happen in the next 30 years, something must have gone terribly wrong, he said, adding that it was possible a medicine against ageing was already among us. We just need to have more evidence that they actually work the way we are hoping, the Harvard professor, who has featured in TIME magazines list of the 100 most influential people in the world, said.

His research has been primarily focused on sirtuins, a group of proteins that appear to be key in regulating the ageing process. In 1999, he was recruited to the Harvard Medical School, where he has been teaching ageing biology and translational medicine for ageing.

Dr Sinclair also shared tips on how to slow the process of ageing: dont eat three regular meals; exercise; lift some weights; use biomarker feedback; sleep well and reduce stress; and eat plants that have been stressed.

You may not want to skip breakfast, you may want to skip lunch or dinner... its different for every individual. If you are young, this is probably not for you, he said, adding that middle-aged people whose metabolism has slowed down should consider skipping meals strategically.

On the question of whether a vegetarian diet was better or a non-vegetarian regimen, he said: You do want your diet to look like what a rabbit might eat more than a lion.

According to a paper published in Nature, Dr Sinclair and his team used an adeno-associated virus as a vehicle to deliver into the retinas of mice three youth-restoring genes that are normally switched on during embryonic development. The three genes, together with a fourth one that was not used in this work, are collectively known as Yamanaka factors. This promoted nerve regeneration following optic-nerve injury in mice with damaged optic nerves, reversed vision loss in animals with a condition mimicking human glaucoma, and reversed vision loss in ageing animals without glaucoma.

Dr Sinclair said on Friday: We are trying to understand can we compress the last few years of life that are sick into a very short period... [The goal] is really not to keep us in nursing homes and being sick for longer. We are not extending old age, we are doing the opposite. Our goal is to extend youthfulness so that we can perhaps live to 90 or 100 and towards the very end, still be productive members of society playing whatever sport you want with your grandkids or great grandkids.

He added: Often, we think that we have reached our maximum life span as a society... that is not true... Over the 20th Century and continuing to today, there is a very linear and predictable increase in human longevity. Every time [people] have said that we have reached the maximum, we blow through that glass ceiling and we keep adding years to life. But they are not all healthy years.

The expert also gave more insights on mortality as a route to tackling ageing. We tend not to die as much as we used to from cardiac reasons, but the brain still ages at the normal rate and we dont do much about it Our approach is to treat the entire body with medicines and lifestyles that will keep every part of the body healthier and more youthful, the expert added. In my scientific opinion, around the age of 30, ageing starts to kick in.

On being asked about the nature of supplements people should take in the quest to slow ageing, the he said: Go with a company that has a good reputation Go for the very pure molecules. He added that resveratrol, a chemical found in red wine, appeared to show benefits in terms of anti-ageing properties. He, however, said that right meals and exercise seem to be the best bet against ageing at this point.

The proof-of-concept study published in Nature demonstrates the epigenetic reprogramming of complex tissues, such as the nerve cells of the eye, to a younger age when they can repair and replace tissue damaged from age-related conditions and diseases. Elaborating on the study in mice, Dr Sinclair said that most of our longevity is determined by our epigenome and not by our DNA.

While the DNA holds instructions for building proteins, epigenome comprises all of chemicals that are added to ones DNA to regulate the activity.

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Pill to reverse ageing in 30 years? Why not, says Harvard professor Dr David Sinclair - Hindustan Times

Aging has implications for a wide range of diseases. Researchers have been looking for ways to halt the aging process for millennia, but such methods remain elusive. Scientists at Harvard Medical School have now offered a glimmer of hope that the aging clock in the eye could be reversedat least in animals.

By reprogramming the expression of three genes, the Harvard team successfully triggered mature nerve cells in mice eyes to adopt a youthful state. The method reversed glaucoma in the mice and reversed age-related vision loss in elderly mice, according to results published in Nature.

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If further studies prove out the concept, they could pave the way for therapies that employ the same approach to repair damagein other organs and possibly treat age-related diseases in humans, the team said.

The researchers focused on the Yamanaka factors, which are four transcription factorsOct4, Sox2, Klf4 and c-Myc. In a Nobel Prize-winning discovery, Shinya Yamanaka found that the factors can change the epigenomehow genes are turned on or offand can thereby transform mature cellsback to a stem cell-like state. It has been hypothesized that changes to the epigenome drive cell aging, especially a process called DNA methylation, by which methyl groups are tagged onto DNA.

Past researches have tried to use the four Yamanaka factorsto turn back the age clock in living animals, but doing so caused cells to adopt unwanted new identities and induced tumor growth.

RELATED:Restoring eyesight with genetically engineered stem cells

To test whether the approach works in living animals, the scientists used adeno-associated virus to deliver the three genes into the retina of mice with optic nerve injuries. The treatment led to a two-fold increase in the number of retinal ganglion cells, which are neurons responsible for receiving and transmitting visual information. Further analysis showed that the injury accelerated DNA methylation age, while the gene cocktail counteracted that effect.

Next the scientists tested whether the gene therapy could also work in disease settings. In a mouse model of induced glaucomawhich is a leading cause of age-related blindness in peoplethe treatment increased nerve cell electrical activity and the animals visual acuity.

But can the therapy also restore vision loss caused by natural aging? In elderly, 12-month-old mice, the gene therapy also restored ganglion cells electrical activity as well as visual acuity, the team reported.

By comparing cells from the treated micewith retinal ganglion cells from young, 5-month-old mice, the researchers found that mRNA levels of 464 genes were altered during aging, and the gene therapy reversed 90% of those changes. The scientists also noticed reversed patterns of DNA methylation, which suggests that DNA methylation is not just the marker but rather the driver behind aging.

What this tells us is the clock doesn't just represent timeit is time. If you wind the hands of the clock back, time also goes backward, the studys senior author, David Sinclair, explained in a statement.

The study marks the first time that glaucoma-induced vision loss was reversednot just slowedin living animals, according to the team.

RELATED:Reprogrammed skin cells restore sight in mouse models of retinal disease

Other researchers are also studying regenerative approaches to treating eye diseases. A research group at the Centre for Genomic Regulation in Barcelona just showed that by modifying mesenchymal stem cells to express chemokine receptors Ccr5 and Cxcr6, retinal tissue could be saved from degeneration.

The idea of reversing age-related decline in humans by epigenetic reprogramming with a gene therapy is exciting, Sinclair said. The Harvard researchers intend to do more animal work that could allow them to start clinical trials in people with glaucoma in about two years.

Our study demonstrates that it's possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function, Sinclair said. If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large.

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Reversing vision loss by turning back the aging clock - FierceBiotech

Dr David Sinclair talks about his experiment and if in the future, a pill can be developed to reverse ageing.

One of the leading experts on ageing, Dr David Sinclair, said on Friday that there is a possibility that people can get a pill in the near future that can reverse ageing. Speaking on the Hindustan Times Leadership Summit (HTLS), Dr Sinclair talked about the experiment carried out on older mice to improve their vision. He added that the way technology is moving, the world might get a pill to rejuvenate themselves.

I dont have a crystal ball but we are working on taking the epigenetic reprogramming technology (the experiment done on older mice) and treat the first patient with glaucoma in the next two years to see if we can restore vision, said Dr Sinclair when asked about the possibility of a pill appearing in the next two or three decades.

There are at least 20 companies which are working on medicine that can slow, and perhaps, reverse ageing. So if it doesnt happen in the next 30 years, something must have gone terribly wrong, he added.

When asked about reusing the epigenetic programming technology, Dr Sinclair said there is a possibility that it can be done a number of times. I think we can do it multiple times, theres no reason why it couldnt be one repeatedly. Imagine, we could find a pill that could do what we did with the eyes of the mice but with the whole body. We have engineered it already to be turned on with a pill.

We used a molecule in those mice, we gave it to them as a drink and it turned on the genes. One day, maybe you can go to your doctor, have an injection or get a pil for three weeks and get rejuvenated - better memory, better eyesight, better healing, maybe even look better. Ten years later, you come back and have another course of that drug, said the biologist.

Dr Sinclair appeared on the cover of the Time Magazines 100 most influential people in the world. He is a professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F Glenn Centre for the Biological Mechanisms of Ageing.

This is the first time that the HTLS is being held virtually owing to the Covid-19 pandemic situation. And in tune with the situation, Defining a New Era has been chosen this years theme. From politics to sports, from medicine to education and food - the summit has seen a wide array of views coming from the experts of the respective fields on post-pandemic world.

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HTLS 2020: A pill that can reverse ageing? Yes, it will be possible, says Dr Sinclair - Hindustan Times

Scientists recently made some impressive developments in the field of age-related diseases. Nonetheless, essentially turning back time on a living creature's DNA remains indefinable and a "Holy Grail."

It is common knowledge that DNA is gradually breaking down as a person gets older. It is seen that such impairment is aging, and various age-related diseases tend to pop up the older an individual gets.

Harvard Medical Schoolresearchers now seem to have a big leap in moving aging backward in mice. More particularly, the scientists managed to invigorate an aging mice's vision by giving them a boost through the use of genes present during early development.

As the scientists explain in a new study Nature published, the work focused on "glaucoma-induced vision impairment in the mice."

(Photo : analogicus on Pixabay)Research findings recently proposed an approach thats safe and could potentially revolutionize the therapeutics of the eye.

The research team used a virus to impact the mice's retinas through the use of a "trio" of what are described as "youth-invigorating genes."

Such genes: Oct4, Sox2, and Klf4, according to the study, are said to be active when the mice's embryos are developing. This, the study authors said, resulted in an intense reversal of the age-related vision problems experienced by mice.

It stimulated the regeneration of nerve while reversing, too, the glaucoma-like occurrences in the animals plagued by it.

With vision loss minus glaucoma that's related to age, the impact was the same, the study specified. More so, the mice regained their previously lost vision.

According to the study's senior author David Sinclair, their research "demonstrates that it is possible to safely reverse the age of complex tissue" like the retina and has its youthful biological role restored."

If confirmed through further research, such results could be transformative for the care of age-associated vision illnesses such as glaucoma and to the areas of biology and medical treatments for illness at large.

As impressive as their study findings were, warn the study authors that they would need to be duplicated in later studies if further development is to be made through the use of such genes for the reversal of loss of vision in other animals and even humans.

A related article BGRposted said this study may be promising, although it is certainly "not ready for human testing yet."

In connection to this new finding, Yuacheng Lu, an HMS research fellow and former ex-doctoral student in Sinclair's lab, developed a gene treatment that could safely reverse the cells' age in living animals.

The work of Lu's develops on Shinya Yamanaka's Nobel Prize-winningdiscovery. Yamanaka discovered the four transcription factors, namely, Oct4, Sox2, Klf4, c-Myc, that could remove epigenetics markers on cells and bring back these cells to their original embryonic state from which they can progress into any cell type.

At this project's onset, Lu explained, many of their colleagues said their approach would not succeed, or it would be dangerous to use it.

The former doctoral student added, their research findings propose this approach "is safe and could potentially revolutionize the therapeutics of the eye," as well as the many other organs impacted by aging.

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Check out more news and information on Agingin Science Times.

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Scientists Uncover Approach That Could Reverse Age-Related Vision Loss - Science Times

Stuff

David Grant Sinclair is on trial in the High Court at Greymouth for the murder of his 10-month-old son.

A Hokitika baby died with 30 bruises all over his body, fractures to his skull and bleeding on the brain and behind both eyes.

The Crown says the fatal injuries were inflicted by his father but his father alleges they were sustained from a fall down the stairs.

David Grant Sinclair is charged with murdering his 10-month-old son, CJ Bodhi White, at Hokitika on July 9, 2019.

A jury trial began on Monday in the High Court at Greymouth before Justice Rebecca Edwards. It is set down for two weeks and 27 witnesses plus Sinclair himself are due to give evidence.

READ MORE:* Suppression lifts on Hokitika man charged with murdering 10-month-old son* West Coast baby allegedly killed by father was 'an angel to us', mother says* Homicide investigation launched in Northland after death of baby

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CJ Bodhi White died aged 10 months in Hokitika on July 9, 2019. His father, David Grant Sinclair, denies murdering the infant.

Crown prosecutor William Taffs said CJ had been in Sinclairs fulltime care for only six weeks before his death.

He said Sinclair told his family, first responders and police he fell asleep with CJ in his bed and was woken between 3am and 4am by a thud from CJ falling out of bed.

Taffs told the jury CJ had not been sleeping well because he was teething and would have been in significant pain from injuries inflicted earlier by his father, including a fractured bone in his foot and bruising to his groin and scrotum.

He said Sinclair put his phone into incognito mode at 3.27am and searched: Does a babys head flop backwards from concussion.

He then accessed several apps including a gambling site and checked the weather forecast.

At 4.17am, he again searched: Why has my 1-year-olds neck gone all floppy after falling out of bed?

He then sent a message to his mother asking her to call him.

When she rang, he told her CJ had fallen out of bed. She arrived at the house less than 10 minutes later, began CPR and rang emergency services.

CJ was unresponsive and was flown to Christchurch Hospital but doctors ruled out surgery because his injuries were unsurvivable. His life support was turned off at 11.40am. He was declared dead 25 minutes later.

CJ had 30 bruises across his body, significant brain injuries, skull fractures, soft swelling to his skull, bleeding to both retinas and swelling, cuts, bleeding and clots on his brain.

Several medical professionals would give evidence that the injuries were not consistent with a fall out of bed on to a carpeted floor. They were consistent with his father hitting his head against a hard object or hitting his head with a hard object, Taffs said.

He had too many bruises in all the wrong places to be accidental. Bruises consistent with finger marks ... inflicted in what the Crown says was a moment of anger or frustration.

Taffs said Sinclair had told medical professionals the historic bruises were caused when he caught CJs leg in the car seat buckle and from CJ hitting himself with a rattle.

Defence lawyer Andrew McKenzie said the jury would be presented with two vastly different scenarios.

He said Sinclair would give evidence that CJ had fallen down the stairs. The defence would also present evidence from experts.

David Sinclair is guilty of taking too much time to call 111. He is guilty of lying to police and lying to people about his baby falling out of bed. He is guilty of not taking steps to remove the risk of his baby falling down the stairs.

He is not guilty of the crime of murder, McKenzie said.

Joanne Carroll/STUFF

The jury trial is set down for two weeks and 27 prosecution witnesses will be called to give evidence.

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