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Old mice grow young again in study. Can people do the same?

In Boston labs, old, blind mice have regained their eyesight, developed smarter, younger brains and built healthier muscle and kidney tissue. On the flip side, young mice have prematurely aged, with devastating results to nearly every tissue in their bodies.

The experiments show aging is a reversible process, capable of being driven “forwards and backwards at will,” said anti-aging expert David Sinclair, a professor of genetics in the Blavatnik Institute at Harvard Medical School and codirector of the Paul F. Glenn Center for Biology of Aging Research.

Our bodies hold a backup copy of our youth that can be triggered to regenerate, said Sinclair, the senior author of a new paper showcasing the work of his lab and international scientists.

The combined experiments, published for the first time Thursday in the journal Cell, challenge the scientific belief aging is the result of genetic mutations that undermine our DNA, creating a junkyard of damaged cellular tissue that can lead to deterioration, disease and death.

“It’s not junk, it’s not damage that causes us to get old,” said Sinclair, who described the work last year at Life Itself, a health and wellness event presented in partnership with CNN.

“We believe it’s a loss of information — a loss in the cell’s ability to read its original DNA so it forgets how to function — in much the same way an old computer may develop corrupted software. I call it the information theory of aging.”

Jae-Hyun Yang, a genetics research fellow in the Sinclair Lab who coauthored the paper, said he expects the findings “will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging.”

Epigenetic changes control aging

While DNA can be viewed as the body’s hardware, the epigenome is the software. Epigenes are proteins and chemicals that sit like freckles on each gene, waiting to tell the gene “what to do, where to do it, and when to do it,” according to the National Human Genome Research Institute.

The epigenome literally turns genes on and off. That process can be triggered by pollution, environmental toxins and human behaviors such as smoking, eating an inflammatory diet or suffering a chronic lack of sleep. And just like a computer, the cellular process becomes corrupted as more DNA is broken or damaged, Sinclair said.

“The cell panics, and proteins that normally would control the genes get distracted by having to go and repair the DNA,” he explained. “Then they don’t all find their way back to where they started, so over time it’s like a Ping-Pong match, where the balls end up all over the floor.”

In other words, the cellular pieces lose their way home, much like a person with Alzheimer’s.

“The astonishing finding is that there’s a backup copy of the software in the body that you can reset,” Sinclair said. “We’re showing why that software gets corrupted and how we can reboot the system by tapping into a reset switch that restores the cell’s ability to read the genome correctly again, as if it was young.”

It doesn’t matter if the body is 50 or 75, healthy or wracked with disease, Sinclair said. Once that process has been triggered, “the body will then remember how to regenerate and will be young again, even if you’re already old and have an illness. Now, what that software is, we don’t know yet. At this point, we just know that we can flip the switch.”

Woman with photo of elderly woman's eyes on hers'

Years of research

The hunt for the switch began when Sinclair was a graduate student, part of a team at the Massachusetts Institute of Technology that discovered the existence of genes to control aging in yeast. That gene exists in all creatures, so there should be a way to do the same in people, he surmised.

To test the theory, he began trying to fast-forward aging in mice without causing mutations or cancer.

“We started making that mouse when I was 39 years old. I’m now 53, and we’ve been studying that mouse ever since,” he said. “If the theory of information aging was wrong, then we would get either a dead mouse, a normal mouse, an aging mouse or a mouse that had cancer. We got aging.”

With the help of other scientists, Sinclair and his Harvard team have been able to age tissues in the brain, eyes, muscle, skin and kidneys of mice.

To do this, Sinclair’s team developed ICE, short for inducible changes to the epigenome. Instead of altering the coding sections of the mice’s DNA that can trigger mutations, ICE alters the way DNA is folded. The temporary, fast-healing cuts made by ICE mimic the daily damage from chemicals, sunlight and the like that contribute to aging.

ICE mice at one year looked and acted twice their age.

Becoming young again

Now it was time to reverse the process. Sinclair Lab geneticist Yuancheng Lu created a mixture of three of four “Yamanaka factors,” human adult skin cells that have been reprogrammed to behave like embryonic or pluripotent stem cells, capable of developing into any cell in the body.

The cocktail was injected into damaged retinal ganglion cells at the back of the eyes of blind mice and switched on by feeding mice antibiotics.

“The antibiotic is just a tool. It could be any chemical really, just a way to be sure the three genes are switched on,” Sinclair told CNN previously. “Normally they are only on in very young, developing embryos and then turn off as we age.”

The mice regained most of their eyesight.

Next, the team tackled brain, muscle and kidney cells, and restored those to much younger levels, according to the study.

“One of our breakthroughs was to realize that if you use this particular set of three pluripotent stem cells, the mice don’t go back to age zero, which would cause cancer or worse,” Sinclair said. “Instead, the cells go back to between 50% and 75% of the original age, and they stop and don’t get any younger, which is lucky. How the cells know to do that, we don’t yet understand.”

Today, Sinclair’s team is trying to find a way to deliver the genetic switch evenly to each cell, thus rejuvenating the entire mouse at once.

“Delivery is a technical hurdle, but other groups seem to have done well,” Sinclair said, pointing to two unpublished studies that appear to have overcome the problem.

“One uses the same system we developed to treat very old mice, the equivalent of an 80-year-old human. And they still got the mice to live longer, which is remarkable. So they’ve kind of beaten us to the punch in that experiment,” he said.

“But that says to me the rejuvenation is not just affecting a few organs, it’s able to rejuvenate the whole mouse because they’re living longer,” he added. “The results are a gift and confirmation of what our paper is saying.”

What’s next? Billions of dollars are being poured into anti-aging, funding all sorts of methods to turn back the clock.

In his lab, Sinclair said his team has reset the cells in mice multiple times, showing that aging can be reversed more than once, and he is currently testing the genetic reset in primates. But decades could pass before any anti-aging clinical trials in humans begin, get analyzed and, if safe and successful, scaled to the mass needed for federal approval.

But just as damaging factors can disrupt the epigenome, healthy behaviors can repair it, Sinclair said.

“We know this is probably true because people who have lived a healthy lifestyle have less biological age than those who have done the opposite,” he said.

His top tips? Focus on plants for food, eat less often, get sufficient sleep, lose your breath for 10 minutes three times a week by exercising to maintain your muscle mass, don’t sweat the small stuff and have a good social group.

“The message is every day counts,” Sinclair said. “How you live your life even when you’re in your teens and 20s really matters, even decades later, because every day your clock is ticking.”

Sandee LaMotte   Jan. 12, 2023

source: www.ctvnews.ca


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Mindful Yoga Can Reduce Risky Behaviors In Troubled Youth

For some young people, dealing with life stressors like exposure to violence and family disruption often means turning to negative, risky behaviors – yet little is known about what can intervene to stop this cycle.

But one long-term study by the University of Cincinnati looks at the link between stressful life events and an increase in substance abuse, risky sexual behaviors and delinquency in a diverse population of 18- to 24-year-old youths. The research also sheds light on distinct coping strategies that can lead to more positive outcomes.

As part of a 10-year study looking at risk-taking and decision-making – or the lack thereof – Jacinda Dariotis, UC public health researcher, spent 12 months focusing on early life stressors as a predictor of risky sexual behavior, substance abuse and delinquency for more than 125 at-risk youths. Surprisingly, she found a small number of the youths were already engaging in constructive coping behaviors on their own that will have positive outcomes later in life.

But what about the majority of troubled youth who cope by engaging in negative, risky and dangerous behaviors?

Results from the most recent segment of Dariotis’ study were presented at the American Public Health Association conference in Atlanta, under the title,”Stress coping strategies as mediators: Toward a better understanding of sexual, substance and delinquency-related risk-taking among transition-aged youth.”

The study revealed that in spite of early life stressors, positive coping behaviors, either learned or self-generated, can actually have a protective effect.

“We found that many of these youths who had endured stressful life events and otherwise would have fallen into the risky behavior trap could actually have positive outcomes later in life because they chose to join in prosocial physical activities, yoga or mindfulness meditation,” says Dariotis.

Risky outlets

During the study, Dariotis looked at the disconnect between the youths who had intended to have positive influences in their lives but continually found themselves engaged in behaviors that had negative outcomes. She found a link between stressful life events and increased risky unprotected sex, violence and substance abuse.

“We took a holistic approach, looking at these issues from a social and biological perspective,” says Dariotis, also director of UC’s College of Education, Criminal Justice and Human Services Evaluation Services Center. “In addition to question-and-answer information, we collected urine samples for drug use confirmation and testosterone levels early in the study to see how hormones played out in negative behaviors.”

According to Dariotis, testosterone can be influential in dominance and aggressive behaviors, but if directed through prosocial behaviors like sports, yoga or healthy competition it can have very positive outcomes.

“If you are the star on your sports team you are succeeding,” says Dariotis. “You can also be competitive academically where you succeed by competing with your peers.”

It’s not that testosterone itself is all bad but it depends on how it is channeled, she adds.

The right track

Before joining UC as an associate professor of research, Dariotis spent the last decade at Johns Hopkins University gathering most of the data that includes neuroimaging and weekly questioning for hundreds of youth from all walks of life.

“I’m particularly interested in teaching at-risk youths to regulate their thoughts, processes and emotions,” says Dariotis. “The neuroimaging allows us to see what’s activated in one’s brain while at rest or performing tasks to help us understand the intersection between hormones, brain structure and activity.”

Dariotis found that at-risk youth who voluntarily spend their time reading books, playing sports or engaged in avoidance coping behaviors were twice as likely to avoid risky sexual behaviors or substance abuse. An example of avoidance coping behaviors, she says, is not thinking about a bad event that had occurred and instead, thinking about what could be better.

Dariotis found youths who were unable to develop positive coping strategies were much more likely to turn to greater risk-taking behaviors that included unprotected sex or sex for money, substance abuse, violence and crime.

Saving time, money and lives

Participating in weekly mindful yoga intervention programs as part of the current study taught the youths how to take control of their breathing and their emotions and helped them develop healthier long-term coping skills.

“These findings highlight the importance of implementing positive coping strategies for at-risk youth particularly for reducing illicit drug use and risky sexual behavior,” says Dariotis. “Mindfulness-based yoga programs designed to improve the ability to cope are needed at earlier ages in schools to help vulnerable youths channel their skills more effectively.”

Given the relative low cost of such programs and easy adaptations to different populations and settings, Dariotis says the return on investment may be substantial especially if they can reduce arrests, repeat offenses and other negative outcomes for risk-taking youth.

Story Source:
Materials provided by University of Cincinnati.   Date:December 7, 2017
Note: Content may be edited for style and length.

Journal Reference:
Jacinda K. Dariotis, Frances R. Chen, Douglas A. Granger. Latent trait testosterone among 18–24 year olds: Methodological considerations and risk associations. Psychoneuroendocrinology, 2016; 67: 1 DOI: 10.1016/j.psyneuen.2016.01.019


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Mental Illness And Teens: It Impacts Every One Of Us

It could be any of us. Any of our kids. Any of our nieces or nephews. Our grandkids. The students in our class. Our friends’ kids. Our neighbours’ kids. Our co-workers’ kids. The list goes on…

The fact is, mental illness impacts more of us than we realize.

The reality is, one in five Canadians will experience mental illness in their lifetime.

Did you know that 10 to 20 per cent of Canadian youth are affected by a mental illness or disorder?

Sadly, only one out of five children who need mental health services receives them.

That is heartbreaking and unacceptable.

So many Canadian youth are struggling with depression and anxiety, and far too many aren’t getting help. Too many young lives have been cut short.

Madeline Grace German Coulter was one of them. That is why The Huffington Post Canada is launching Frame Of Mind, a new blog series inspired by The Maddie Project that will focus on teens and mental health.

The series aims to raise awareness and spark a conversation by speaking directly to teens who are going through a tough time, as well as their families, teachers and community leaders. We want to ensure that teens who are struggling with mental illness get the help, support and compassion they need.

youth

 

Kicking off our conversation

The series is running over four weeks and we start with a deeply moving blog from Glen Canning on his message to youth who are struggling and have lost hope. Mental health superhero Alicia Raimundo shares her inspiring story, and professional golfer Andrew Jensen explains why he talks about depression.

Nicole German writes about losing her daughter Maddie and why empathy is so important in mental health. Maddie’s father, Chris Coulter, writes about the real pain of depression. We also have blogs on the heartbreak of teen suicide, the complicated teenage brain and many more important topics.

Why talk about it?

From time to time I hear people flippantly say, “That is sad, I don’t want to read about that” or “That doesn’t impact me.” What many people don’t realize is that avoiding reading about something or talking about it doesn’t make the issue go away. I would argue that it contributes to the problem.

The propensity to avoid sadness and uncomfortable topics in society is akin to putting one’s head in the sand. What good is it going to serve? How will that help people who are struggling? How will services improve? How will that move policies and funding forward?

It is only when we put ourselves in someone else’s shoes and listen and empathize that we better understand their struggles, mindsets and frustrations.

The future is bright

Over the coming weeks, blogs in our series will be addressing symptoms of depression and anxiety, mental health in the classroom, bullying, the link between social media and depression, tips to protect your child’s mental health, suicide prevention and many more topics.

Carol Todd, Kids Help Phone, The Canadian Mental Health Association, The Centre for Addiction and Mental Health, former Olympians Silken Laumann and Ian Warner, parenting expert Alyson Shafer, teachers, psychologists, counsellors and dozens more will be sharing their stories, perspectives, words of advice and inspiring messages of hope.

It is blogs at their best. Personal, insightful and inspiring.

We hope you enjoy the series and learn more about how you can help teens who are struggling. Please follow along, comment, share and join the conversation.

It truly has been a passion project for us here at HuffPost Canada. Thanks to all those who have contributed to the series. Talking about youth mental illness and suicide prevention isn’t easy, but our bloggers have done so with so much grace, bravery, honesty and compassion.

They have shown that we can only truly understand one another and better understand youth mental illness when we respect each other’s Frame Of Mind.

If you or someone you know is at risk
please contact your nearest Crisis Centre
or call Kids Help Phone at 1-800-668-6868
to speak to a counsellor.
If you would like to contribute a blog to Frame Of Mind, please email cablogteam@huffingtonpost.com
09/07/2016      Amy Gibson
Managing Editor of Blogs, Huffington Post Canada