A Krishanu Saha, assistant professor, biomedical engineering and medical history and bioethics, University of Wisconsin-Madison:
Editing genes involves changing the sequence of letters in the DNA. Researchers like to edit genes so they can understand the function of them, particularly genes that relate to various types of disorders that physicians have seen in the clinic. We can use this information to generate new hypotheses of how genes influence diseases.
Historically, editing the genome has been difficult. Several editing technologies go into cells and essentially use “genetic scissors” to cut up the DNA. Once you introduce a cut into the genome, repair processes will try to repair that break. This repair often occurs in imprecise ways that could potentially cause errors and mutations.
Instead, you could take advantage of those repair processes to have the genome incorporate a foreign piece of DNA that has the letters that you want to be inserted.
Such editing has been done in human cells for the last 15-20 years using a set of proteins called nucleases. Nucleases are engineered proteins that cut DNA.
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Recently, the Cas9 nuclease, part of the CRISPR system, has really accelerated the pace of editing throughout biology and engineering.
To give you a frame of reference, about 10 years ago it cost about $50,000 to make only one precise cut in the genome. Attaining high precision was challenging: essentially finding a needle in a haystack, meaning editing one stretch of letters among 3 billion letters in the human genome. Understandably that was hard, and it took a lot of work to engineer the nucleases.
In the years since then, with the advent of the CRISPR system, a component called a guide RNA is used to attain precise editing. It’s easy to make the guide RNA, and this enables us to easily go after multiple parts of the genome at once. These components can be made very quickly on the order of a few dollars rather than thousands of dollars, making the technology more accessible for research.
Blue Sky Science is a collaboration of the Wisconsin State Journal and the Morgridge Institute for Research.
She has Native American in her family tree going back generations, according to a report Monday.
Carlos D. Bustamante, a Stanford University professor and expert in the field, determined in his analysis that a pure Native American ancestor appears in Warren’s family “in the range of 6-10 generations ago,” the Boston Globe reported.
That’s consistent with the Massachusetts Democrat’s family lore from her Oklahoma upbringing that her great-great-great-grandmother, O.C. Sarah Smith, was partially Native American.
Bustamante, who won a 2010 MacArthur Fellowship, also known as a Genius Grant, found that the “vast majority” of Warren’s ancestry is European, but “the results strongly support the existence of an unmixed Native American ancestor.”
The release of the DNA findings appear to be a way for Warren, who is expected to run for president in 2020, to put the issue to rest and remove a talking point for her opponents.
“Now, the president likes to call my mom a liar. What do the facts say?” she asks him.
“The facts suggest that you absolutely have a Native American ancestor in your pedigree,” he replies.
Tamping down accusations made by many Republicans that she parlayed her heritage to benefit her career, the video includes a number of law professors — including from Harvard Law and the University of Pennsylvania Law School — attesting that she was hired for her ability.
“Her heritage had no bearing on her hiring. Period,” Jay Westbrook, a professor at the University of Texas Austin School of Law, says in the video.
Warren also includes family members in the video who call out Trump for mocking her.
“He’s talking about stuff he doesn’t have any idea about,” says her nephew Mark Herring.
Warren herself also addresses Trump’s “Pocahontas” comments, saying “my family history is my family history.”
“This isn’t just about casual racism — war-hoops and tomahawk chops. Native Americans have faced discrimination, neglect and violence for generations,” she says in the video. “And President Trump can say what he wants about me, but mocking Native Americans or any group in order to get at me — that’s not what America stands for.”
Will Churches And Parents Ever Quit Lying To Children About Christmas?
This post today is about one main issue; Santa Clause. I am not saying that all parents, Christian or not, lie too their children and tell them that there is really a Santa and flying Reindeer. But at least here in America it does seem that this fantasy is one that is easy to go along with when your children are in the 3, 4, 5-year-old range. But, there reaches a point with every child where they find out that Mom and Dad have been lying to them all of their life. Why, why do so many parents ‘just go along with this’ until we reach a point where our kids are going to realize that Mom and Dad will lie to you because they have proven themselves to be liars. I have heard people a few times in my life say ‘not to ruin Christmas’ for the young kids by telling them that there is no Santa. What do they mean by ‘ruin Christmas’? If you take Santa out of Christmas what would the children have then? How about the truth? Tell your kids the Christmas birth of celebration of a baby child call Jesus. Even if you do not believe in the Christian faith letting your children know what the truth behind the question, why is there such a thing as Christmas? Even if you are Jewish, Islamic, Hindi, Buddhist, or of no faith at all, do you really want one of the first lessons your child learns about you is that you lie to them? Why can’t people just be truthful with each other, is it truly in our DNA to be liars?
In this paragraph I am calling out not just Christian parents but some of the Churches themselves. I have seen and heard first hand of community Churches where even the Pastor is the one who dresses up as Santa for plays inside the Church building. I may be old-fashioned in some of your eyes, but so be it. I know that no one can please everyone, even Jesus was/is hated, so I have learned to only concern myself with trying to please Jesus, then let all of life’s other cards just fall where ever they fall. I personally would like to know how telling our children the ‘Jesus story’ ‘ruins Christmas’? What is wrong with telling your kids that you took a part-time job this fall so that you could have the money to buy your kids a few things extra at Christmas school break? What is wrong with your kids seeing the correlation between how hard Mom and Dad are working so that their kids can have a good Christmas? Is it wrong if our small children learn of the ‘3 wise man’ whom brought gifts to the new-born child as a model for people giving gifts to their own children? Why do so many people whom call themselves Christians have Santa and crew on their front lawns? Why do some Churches do the same? Truth, what is truth? There is only one ‘Truth’, and it is not your version, or mine. We can make-up and say anything, we can call our stories ‘the truth’ if we want to but if we are not telling the actual truth, then the word for us is liars. Now, is Santa real, or is he a lie? What are we telling our children, the truth, or lies?
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The mummified specimen from Atacama region of Chile.
An unusual skeleton found in Chile has perplexed people for more than a decade
Whole genome sequencing revealed what caused its abnormalities
(CNN)A mummified skeleton discovered in Chile’s Atacama Desert 15 years ago doesn’t look like anyone you’ve ever met. In fact, some would say it looks, well, alien.
It’s a skeletal conundrum made up of perplexing features. It’s only 6 inches tall — but initial estimates of the age of the bones were consistent with a child aged 6 to 8 years.
The long, angular skull, slanted eye sockets and fewer than normal ribs — 10 pairs rather than the normal 12 — only deepened the mystery.
Questions surrounding the discovery led to speculation that it was a previously unidentified primate or even an extraterrestrial life form.
The skeleton, dubbed Ata, was featured in TV shows and a documentary, “Sirius,” in which a UFO researcher attempts to figure out Ata’s origins.
Now, the authors of a study based on five years of genomic analysis want to set the record straight: Ata is human, albeit one with multiple bone disease-associated mutations. And they believe that their findings, published Thursday in the journal Genome Research, could help diagnose genetic mutation-based cases for living patients.
In 2003, Ata was found in a deserted mining town called La Noria, in Chile’s Atacama region. It was thought to be ancient at first, but initial analysis conducted in 2012 proved that the skeleton was only about 40 years old.This meant DNA would still be intact and could be retrieved for study.
The widespread speculation surrounding Ata brought the case to the attention of Gary Nolan, senior author of the new study and professor of microbiology and immunology at Stanford University.
“I learned about this through a friend who was interested in the entire area of extraterrestrial life,” Nolan wrote in an email. “He told me about a documentary coming out (‘Sirius’ … you can find it on Netflix now) which was to feature the ‘Atacama Humanoid.’
It was claimed that this was possibly the mummy of an alien.
“That was a significant claim in and of itself. More shocking though was the picture I was provided that was part of the online publicity. I decided to contact the movie directors (basically on a dare …) to tell them it was possible to do a sequencing of the specimen (if it had earthly DNA …) to determine its origin.”
Nolan and his colleagues signed a confidentiality agreement, and the directors agreed to report Nolan’s findings, even if the results indicated that Ata’s DNA was human.
Nolan wanted to study Ata for several reasons. The extraordinary specimen could have been a previously unrecognized primate species, some sort of human deformity or something else entirely. Nolan said he and his colleagues never believed it could be an alien.
They wanted an answer to the basic question: “What is it?”
DNA analysis would tell the true story. A sample extracted from the bone marrow of Ata’s ribs was used to conduct a whole-genome sequence analysis.
It was compared with human and primate genomes and determined to be a human female, probably a fetus, with Chilean ancestry. Although dating initially estimated the bone age of the skeleton at between 6 and 8 years, the researchers found that the remains had a rare bone-aging disorder that made them seem older than the person they belonged to.
At first, 8% of the DNA didn’t match with human DNA. Researchers determined that this was because of a degraded sample. An improved analysis matched up to 98%, Nolan said. Given the exposure and age of the skeleton, this wasn’t surprising. Then, they moved on to diagnosing the abnormalities.
It’s all in the genes
The researchers were looking for what might explain the skeleton’s small stature, as well as the abnormal rib count and other bone and skull oddities.
Dr. Atul Butte, another senior author of the study, was brought in to assist with evaluating the genome. Butte, the Priscilla Chan and Mark Zuckerberg distinguished professor and director of the Institute for Computational Health Sciences at the University of California, San Francisco, treated the analysis as though it were for a patient.
It revealed a number of mutations within seven genes. Together, these created bone and musculoskeletal deformities, like scoliosis, and skeletal dysplasia, known as dwarfism.
“There are mutations in many genes, including genes involved with the production of collagen (in our bones and hair), joints, ribs, and arteries,” Butte wrote in an email. “We know these genes are involved with these processes in human development, but we are still learning what all the other genes in the DNA do.”
Although the mutations found within the genes are known to cause bone disease, some of them had not been previously connected to growth or developmental disorders. The combination of genetic mutations explains Ata’s appearance, but it’s the number of mutations all present in the same specimen that surprised the scientists.
“It’s rare,” Butte said. “To our knowledge, no one has ever explained all of these symptoms in a patient before, and the changes in the DNA, or mutations, reflects this.”
But what could have caused this number of mutations?
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“Many times, genetic diseases are passed on from parents that are carriers,” Butte said. “In this case, these mutations are so rare that we haven’t actually ever seen some of these before, so it’s hard to imagine there are carriers out there. We do speculate that the environment where this child was developing might have played a role. The specimen was found in a town with abandoned nitrate mines, and exposure to nitrates might have caused the mutations. But it’s only speculation.”
No other researchers have seen the remains.
The way Nolan, Butte and their colleagues used their analytical tools to understand the mysteries presented by Ata’s skeleton may provide a pathway for analysis of multiple genes to discover the roots of mutations.
Butte said he hopes that the technology and tools used in this study can help patients and their families receive diagnoses quicker, as well as helping to develop treatments for conditions that can be traced to genetic mutations.
“Many children’s hospitals now see patients or children with unusual syndromes, including those never described before,” Butte said.
“DNA sequencing is now more commonly used to help us solve these ‘undiagnosed diseases.’ But many times, we tend to search for a single gene mutation that might explain what we see in the patient.
“What this case taught me we that sometimes there might actually be more than one major DNA difference involved in explaining a particularly hard-to-explain patient. We shouldn’t stop a search when we’ve found the first relevant mutation; indeed there might be many others also involved.”
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Neanderthals, Denisovans and our ancestors were mixing and mingling a long time ago — and some of our genetics can be traced back to these archaic humans.
In Asians, as much as 3% of an individual’s DNA may be Neanderthal. For Europeans, it’s as much as 2%. A new study has found that our ancestors interbred with two distinct Denisovan populations, increasing the probability of the presence in modern populations of DNA inherited from this ancient and mysterious people.
“It is amazing that we can look into human history via current-day human genetic data, and determine some of the events that happened in the past,” study author Sharon Browning wrote in an email. Browning is a research professor with the University of Washington’s Department of Biostatistics.
“In particular, in this study we found two distinct episodes of Denisovan admixture, which adds to what was previously known about the contribution of Neanderthals and Denisovans to our genomes today.”
Denisovans pose particular questions for scientists because researchers have only a few bones that even point to their existence: a finger bone, toe bone and a couple of teeth. Fossilized DNA sequenced from those bones, recovered in Siberia, has allowed us to learn more about them. But we still don’t know what these extinct hominins looked like.
Neanderthal and Denisovan DNA was sequenced completely for the first time in 2010, which led to the initial discovery that they were interbreeding with our ancestors. Studies found that the population of Oceania and Papua New Guinea received the most DNA from Denisovans, around 5%.
Fifty thousand years ago, as modern humans moved out of Africa, they encountered Neanderthals and Denisovans, and the “admixing” happened. But pinning down exactly where it happened has proved difficult.
It was especially puzzling given that the fossils were found in Siberia, but Denisovans are most strongly connected to Oceania.
Denisovan ancestry was also present in Asia, although researchers believed that this occurred through migration from Oceania.
Comparing the Denisovan genome to that of 5,600 Europeans, Asians, Americans and Oceanians painted a different picture.
The data showed that Denisovans were even more closely related to modern East Asians, specifically Han Chinese, Chinese Dai and Japanese, than those from Papua New Guinea. And this second set of Denisovan ancestry was different from Oceanians and Papuans.
“It makes it clear that there were distinct populations of Denisovans, rather than a single population,” Browning said. “The fact that these populations had diverged somewhat from each other suggests that the two populations were not mixing very often with each other, perhaps due to geographical separation.”
A possible explanation is that our Oceanian ancestors encountered a southern group of Denisovans, while East Asians met a northern group.
“(This) led people to suspect that Denisovans did not just live in Siberia, but also lived elsewhere in Asia, somewhere south along the likely routes that the ancestors of Oceanians may have taken to get to Oceania,” Browning said. “This study makes this hypothesis look very likely.”
This could also mean that there were more than two distinct episodes of Denisovans mixing with modern humans, which Browning believes future analysis could reveal.
“A major novel finding is that some populations (East Asians) have evidence of multiple introgression related to Denisovans while a few others (South Asians, Papuans) have evidence of a single Denisovan introgression,” Sriram Sankararaman said in an email. “The Denisovan ancestry in South Asians is quite diverged from the sequence Denisovan while the additional component in East Asians is quite close. This suggests a complex interaction pattern of the Denisovans and modern human populations in mainland Asia.”
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Sankararaman, who was not involved in the study, has worked on Denisovan research and is an assistant professor at the University of California, Los Angeles, in the department of computer science and the department of human genetics.
Going forward, Browning and her colleagues plan to study other populations to look for signatures of admixture with archaic humans besides Neanderthals and Denisovans.
“I’d love to delve further into Neanderthal ancestry, and understand why East Asians have a higher rate of Neanderthal ancestry — around 3% — compared to Europeans — around 2%,” Browning said.
“It has been hypothesized that the extra Neanderthal ancestry in East Asians is due to an additional admixture event, but we didn’t find a clear sign of that in our study. That doesn’t rule out this possibility — we might need to dig a little deeper to find it.”
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Who do you consider your family to be? I know from raising this subject within small groups that people have a wide variety of answers to that simple question. Some people only feel that their immediate household is their family, you know, Mom, Dad, and siblings. I have met quite a few people who have even divorced some of or all of those people from their lives. I have met many people who are by blood siblings or parents of friends that I know well, whom when you met them you see why your friends have no use for this or that blood relative. When I was growing up I was inundated by alcoholics who were also close blood and of course those they chose to hang around and guzzle the suds with. These days it seems that drugs like crack and meth are the vehicle which is totally ripping families apart. When people get hooked on those chemicals they usually find themselves unemployed and homeless when they have used up all of their friends and family because they will steal from anyone to get another high. After a while even close family members tell them to never darken their doorway again. Of course there are many other reasons also that causes families to fall apart, to me, either which way you look at this issue it is sad when brother won’t speak to his brother, or parent to child.
My wife as well as a few other people throughout my life have told me they think I’m nuts because to me once you are family, you are always family. I have at times joked that I must have some Italian blood in my veins because of how I feel about this issue. I know that I don’t, my tree just goes back to Norway, Ireland, Scotland, and England so I’m just a Scandinavian area mutt. The only brother that I ever knew (one brother died before I was born) was married three times before he died from an aneurysm at the age of 43. He was seven years older than me and so he was out whoring around well before I was. Each of the three ladies that he married already had kids when he married them. He had one child with each of them but there were/are 18 kids that weren’t his. Don’t think that I am trying to get uppity on my brother now because I myself have been married three times also. Total I have two blood kids of my own and I have two-step kids that to me are my kids as if they were blood, I love all four of them. They are all four grown and I have seven grand-kids now, I consider myself to be a very fortunate person.
About everyone I know thinks we have got this in our DNA of caring, or we don’t. I am from a small core family of five, so to me once a person or persons are family, you are always family. Should I not speak with former in-laws of my own or of my brother just because of a divorce? Do you just stop communicating with people that you grew to love as if they just don’t matter anymore? To me it is difficult to stop loving someone who you have honestly loved. You see, to me all of my brothers kids and step kids are my nephews and nieces and they always will be, just as his three x-wives will always be sisters to me.
What is your opinion on my line of thoughts and beliefs about family? Do you think I am just plain odd that I would count people as family the way I do? What is your opinion on whom you consider to be in your heart? I have met a few people who when they got old enough to get out on their own they totally divorced themselves from everyone they knew usually because of how they were treated in their growing up years. To me that would be a sad personal situation for any person to be in but I have also know of parents who put their kid on the street and told them to never come to their door again. It is sad for people to have such splits in their lives, it really doesn’t surprise me why many people only consider people who are not blood, to be their real family. Well, if you would, drop me a line on your thought’s of what or who, that you consider to make up a family. Thank you for your time, I appreciate you stopping in. Goodnight and God’s blessings I pray for you and your family, (inner circle).—Oldpoet56
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The process is very tightly controlled and timed in the human body – some eggs will mature during the teenage years, others more than two decades later.
An egg needs to lose half its genetic material during development, otherwise there would be too much DNA when it was fertilised by a sperm.
This excess is cast off into a miniature cell called a polar body, but in the study the polar bodies were abnormally large.
“This is a concern,” said Prof Telfer. But it is one she thinks can be addressed by improving the technology.
Work on mouse eggs, which was nailed 20 years ago, showed the technology could be used to produce live animals.
Matching this achievement in human tissue could eventually be used to help children having cancer treatment.
Chemotherapy and radiotherapy risks making you sterile.
Women can freeze matured eggs, or even embryos if they are fertilised with a partner’s sperm, before starting treatment – but this is not possible for girls with childhood cancers.
At the moment they can have ovarian tissue frozen before treatment, which is then put back in to mature years later if the patient wants children of their own.
But if there are any abnormalities in the frozen sample then doctors will think it is too risky.
Being able to make eggs in the lab would be a safer option for those patients.
Mr Stuart Lavery, a consultant gynaecologist at Hammersmith Hospital, said: “This work represents a genuine step forward in our understanding.
“Although still in small numbers and requiring optimisation, this preliminary work offers hope for patients.”
It would be legal to fertilise one of the lab-made eggs to create an embryo for research purposes in the UK.
But the team in Edinburgh do not have a licence to carry out the experiment. They are discussing whether to apply to the embryo authority for one, or collaborate with a centre that already has one.
Prof Azim Surani, the director of germline research at University of Cambridge’s Gurdon Institute, said: “Molecular characterisation and chromosomal analysis is needed to show how these egg cells compare with normal eggs.
“It might be of interest to test the developmental potential of these eggs in culture to blastocyst stage, by attempting IVF.”
(THIS ARTICLE IS COURTESY OF NAUTILUS: SCIENCE AND AUTHOR ANIL ANANTHASWAMY)
In 1979, psychologist Ellen Langer and her students carefully refurbished an old monastery in Peterborough, New Hampshire, to resemble a place that would have existed two decades earlier. They invited a group of elderly men in their late 70s and early 80s to spend a week with them and live as they did in 1959, “a time when an IBM computer filled a whole room and panty hose had just been introduced to U.S. women,” Langer wrote. Her idea was to return the men, at least in their minds, to a time when they were younger and healthier—and to see if it had physiological consequences.
Every day Langer and her students met with the men to discuss “current” events. They talked about the first United States satellite launch, Fidel Castro entering Havana after his march across Cuba, and the Baltimore Colts winning the NFL championship game. They discussed “current” books: Ian Fleming’s Goldfinger and Leon Uris’ Exodus. They watched Ed Sullivan and Jack Benny and Jackie Gleason on a black-and-white TV, listened to Nat King Cole on the radio, and saw Marilyn Monroe in Some Like It Hot. Everything was transporting the men back to 1959.
When Langer studied the men after a week of such sensory and mindful immersion in the past, she found that their memory, vision, hearing, and even physical strength had improved. She compared the traits to those of a control group of men, who had also spent a week in a retreat. The control group, however, had been told the experiment was about reminiscing. They were not told to live as if it were 1959. The first group, in a very objective sense, seemed younger. The team took photographs of the men before and after the experiment, and people who knew nothing about the study said the men looked younger in the after-pictures, says Langer, who today is a professor of psychology at Harvard University.
Langer’s experiment was a tantalizing demonstration that our chronological age based on our birthdate is a misleading indicator of aging. Langer, of course, was tackling the role of the mind in how old we feel and act. Since her study, others have taken a more objective look at the aging body. The goal is to determine an individual’s “biological age,” a term that aims to capture the body’s physiological development and decline with time, and predict, with reasonable accuracy, the risks of disease and death. As scientists have worked to pinpoint a person’s biological age, they have learned that organs and tissues often age differently, making it difficult to reduce biological age to a single number. They have also made a discovery that echoes Langer’s work. How old we feel—our subjective age—can influence how we age. Where age is concerned, the pages torn off a calendar do not tell the whole story.
While we intuitively know what it means to grow old, precise definitions of aging haven’t been easy to come by. In 1956, British gerontologist and author Alex Comfort (later famous for writing The Joy of Sex) memorably defined senescence as “a decrease in viability and an increase in vulnerability.” Any given individual, he wrote, would die from “randomly distributed causes.” Evolutionary biologists think of aging as something that reduces our ability to survive and reproduce because of “internal physiological deterioration.” Such deterioration, in turn, can be understood in terms of cellular functions: The older the cells in an organ, the more likely they are to stop dividing and die, or develop mutations that lead to cancer. This leads us to the idea that our bodies may have a true biological age.
The road to determining that age, though, has not been a straight one. One approach is to look for so-called biomarkers of aging, something that’s changing in the body and can be used as a predictor of the likelihood of being struck by age-related diseases or of how much longer one has left to live. An obvious set of biomarkers could be attributes like blood pressure or body weight. Both tend to go up as the body ages. But they are unreliable. Blood pressure can be affected by medication and body weight depends on lifestyle and diet, and there are people who certainly don’t gain weight as they age.
Where age is concerned, the pages torn off calendar do not tell the whole story.
In the 1990s, one promising biomarker stood out: stretches of DNA called telomeres. They appear at the ends of chromosomes, serving as caps that protect the chromosomes from fraying. Telomeres have often been likened to the plastic tips that similarly protect shoelaces. It turns out that telomeres themselves get shorter and shorter each time a cell divides. And when the telomere shortens beyond a point, the cell dies. There’s a strong relationship between telomere length and health and diseases, such as cancer and atherosclerosis.
But despite a range of studies trying to find such a link, it’s been hard to make the case for telomeres as accurate biomarkers of aging. In 2013, Anne Newman, director of the Center for Aging and Population Health at the University of Pittsburgh, and her student Jason Sanders reviewed the existing literature on telomeres and concluded that “if telomere length is a biomarker of human aging, it is a weak biomarker with poor predictive accuracy.”
“Twenty years ago, people had high hopes that telomere length could actually explain aging, as in biological aging. There was a hope that it would be the root cause of aging,” says Steve Horvath, a geneticist and biostatistician at the University of California, Los Angeles. “Now we know that that’s simply not the case. In the last 10 to 15 years, people realized that there must be other mechanisms that play an important role in aging.”
Attention shifted to how fast stem cells are being depleted in the body, or the efficacy of mitochondria (the organelles inside our cells that produce the energy needed for cells to function). Horvath scoured the data for reliable markers, looking at, for example, levels of gene expression for any strong correlations to aging. He found none.
But that didn’t mean there weren’t reliable biomarkers. There was one set of data Horvath had been studiously avoiding. This had to do with DNA methylation, a process cells use to switch off genes. Methylation mainly involves the addition of a so-called methyl group to cytosine, one of the four main bases that make up strands of DNA. Because DNA methylation does not alter the core genetic sequence, but rather modifies gene expression externally, the process is called epigenetics.
Horvath didn’t think that epigenetics would have anything to do with aging. “I had data sitting there and I would not really touch them, because I thought there was no meaning in it anyway,” he says.
But some time in 2009, Horvath gave in and analyzed a dataset of methylation levels at 27,000 locations on the human genome—an analysis “you can do in an hour,” he says. Nothing in his 10 years of analyzing genomic datasets had prepared him for the results. “I had never seen anything like it,” he says. “It’s a cliché, but it really was a smoking gun.”
Because their minds were taken back to a time when they were younger, their bodies went back too.
After a few more years of “labor intensive” work, Horvath identified 353 special sites on the human genome that were present in cells in every tissue and organ. Horvath developed an algorithm that used the methylation levels at these 353 sites—regardless of the cell type—to establish an epigenetic clock. His algorithm took into account that in some of these 353 sites, the methylation levels decreased with age, while in others they increased.
In 2013, Horvath published the results of his analysis of 8,000 samples taken from 51 types of healthy tissue and cells, and the conclusions were striking. When he calculated a single number for the biological age of the person based on the weighted average of the methylation levels at the 353 sites, he found that this number correlated well with the chronological age of the person (it was off by less than 3.6 years in 50 percent of the people—a far better correlation than has been obtained for any other biomarker). He also discovered that for middle-aged people and older, the epigenetic clock starts slowing down or speeding up—providing a way of telling whether someone is aging faster or slower than the calendar suggests.
Despite the correlation, Horvath says that biological age, rather than being for the whole body, is better applied to specific tissues and organs, whether it’s bone, blood, heart, lungs, muscles, or even the brain. The difference between the biological age and chronological age can be negative, zero, or positive. A negative deviation means that the tissue or organ is younger than expected; a zero indicates that the tissue is aging normally; and a positive deviation means the tissue or organ is older. Data show that different tissues can age at different rates.
In general, diseases speed up the epigenetic clock, and this is particularly striking in patients with Down’s syndrome or in those infected with HIV. In both cases, the tissues tend to age faster than normal. For instance, the blood and brain tissue in those infected with HIV show accelerated aging. Obesity causes the liver to age faster. And studies of people who died of Alzheimer’s disease show that the prefrontal cortex undergoes accelerated aging. Horvath also analyzed 6,000 samples of cancerous tissue and found that the epigenetic clock was ticking much faster in such cases, showing that the tissue had aged significantly more than the chronological age.
Despite this wealth of data, there is a gaping hole in our understanding of this striking correlation between methylation markers and biological age. “The biggest weakness of the epigenetic clock is that we just don’t understand the precise molecular mechanism behind it,” says Horvath. His speculation—and he stresses it’s just speculation—is that the epigenetic clock is related to what he calls the “epigenetic maintenance system,” molecular and enzymatic processes that maintain the epigenome and protect it from damage. “I feel that these markers are a footprint of that mechanism,” says Horvath. But “why is it so accurate? What pathway relates to it? That’s the biggest challenge right now,” he adds.
Even without understanding exactly how and why it works, the epigenetic clock gives researchers a tool to test the efficacy of anti-aging interventions that can potentially slow aging. “It’d be very exciting to develop a therapy that allows us to reset the epigenetic clock,” says Horvath.
While Horvath is thinking about hormonal treatments, Langer’s work with elderly men at the monastery in New Hampshire suggests that we can use the power of our mind to influence the body. Langer didn’t publish her results in a scientific journal in 1979. At the time, she didn’t have the resources to do a thorough study for the leading journals. “When you run a retreat over the course of five days, it’s very hard to control for everything,” Langer says. “Also, I didn’t have the funds to have, for instance, a vacationing control group. I could have published it in a second-rate journal, but I didn’t see any point to that. I wanted to get the information out there and I wrote it first in a book for Oxford University Press, so it was reviewed.”
Also, her argument that mind and body are one was potentially a little too path-breaking for the journals. “I think they were unlikely to buy the theoretical part of it,” she says. “The findings, improving vision and hearing in an elderly population, were so unusual that they were not going to rush to publish and stick their necks out.” Since then, Langer has pursued the mind-body connection and its effects on physiology and aging in rigorous studies that have been published in numerous scientific journals and books.
Traditionally, the mind-body problem refers to the difficulty of explaining how our ostensibly non-material mental states can affect the material body (clearly seen in the placebo effect). To Langer, the mind and body are one. “Wherever you put the mind you are necessarily putting the body,” she says.
So Langer began asking if subjective mental states could influence something as objective as the levels of blood sugar in patients with Type 2 diabetes. The 46 subjects in her study, all suffering from Type 2 diabetes, were asked to play computer games for 90 minutes. On their desk was a clock. They were asked to switch games every 15 minutes. The twist in the study was that for one-third of the subjects, the clock was ticking slower than real time, for one-third it was going faster, and for the last third, the clock was keeping real time.
Most of us are slaves to our chronological age.
“The question we were asking was would blood sugar level follow real or perceived time,” says Langer. “And the answer is perceived time.” This was a striking illustration of psychological processes—in this case the subjective perception of time—influencing metabolic processes in the body that control the level of blood sugar.
Although Langer did not explore a connection between the mind and epigenetic changes, other studies suggest such a link. In 2013, Richard Davidson of the University of Wisconsin at Madison and his colleagues reported that even one day of mindfulness meditation can impact the expression of genes. In their study, 19 experienced meditators were studied before and after a full day of intensive meditation. For control, the researchers similarly studied a group of 21 people who engaged in a full day of leisure. At the end of the day, the meditators showed lowered levels of activity of inflammatory genes—exactly the kind of effect seen when one takes anti-inflammatory drugs. The study also showed lowered activity of genes that are involved in epigenetically controlling expressions of other genes. The state of one’s mind, it seems, can have an epigenetic effect.
Such studies taken together provide clues as to why the week-long retreat in New Hampshire reversed some of the age-related attributes in elderly men. Because their minds were taken back to a time when they were younger, their bodies too went back to that earlier time, bringing about some of the physiological changes that resulted in improved hearing or grip strength.
But it’s important to point out that biological aging is an inexorable process—and there comes a time when no amount of thinking positive thoughts can halt aging. If body and mind are one and the same—as Langer suggests—then an aging body and aging mind go hand-in-hand, limiting our ability to influence physiological decline with psychological deftness.
Still, Langer thinks that how we age has a lot to do with our perceptions of what aging means—often reinforced by culture and society. “Whether it’s about aging or anything else, if you are surrounded by people who have certain expectations for you, you tend to meet those expectations, positive or negative,” says Langer.
Most of us are slaves to our chronological age, behaving, as the saying goes, age-appropriately. For example, young people often take steps to recover from a minor injury, whereas someone in their 80s may accept the pain that comes with the injury and be less proactive in addressing the problem. “Many people, because of societal expectations, all too often say, ‘Well, what do you expect, as you get older you fall apart,’ ” says Langer. “So, they don’t do the things to make themselves better, and it becomes a self-fulfilling prophecy.”
It’s this perception of one’s age, or subjective age, that interests Antonio Terracciano, a psychologist and gerontologist at Florida State University College of Medicine. Horvath’s work shows that biological age is correlated with diseases. Can one say the same thing about subjective age?
People’s perception of their own age can differ markedly from person to person. People between the ages of 40 and 80, for example, tend to think they are younger. People who are 60 may say that they feel like they are 50 or 55, or sometimes even 45. Rarely will they say they feel older. However, people in their 20s often perceive their age to be the same as their chronological age, and may say they feel somewhat older.
Terracciano and colleagues have found that subjective age correlates with certain physiological markers of aging, such as grip strength, walking speed, lung capacity, and even the levels of C-reactive protein in the blood, an indication of inflammation in the body. The younger you feel you are, the better are these indicators of age and health: You walk faster, have better grip strength and lung capacity, and less inflammation.
Subjective age affects cognition and is an indicator of the likelihood of developing dementia. Terracciano and colleagues looked at data collected from 5,748 people aged 65 or older. The subjects’ cognitive abilities were evaluated to establish a baseline and they were then followed for a period of up to four years. The subjects were also asked about how old they felt at each instance. The researchers found that those who had a higher subjective age to start with were more likely to develop cognitive impairments and even dementia.
These correlation studies have limitations, however. For example, it’s possible that physically active people, who have better walking speed and lung capacity, and lower levels of C-reactive protein in their blood, naturally feel younger. How can one establish that our subjective age influences physiology and not the other way around?
That’s exactly what Yannick Stephan of the University of Grenoble in France and colleagues tried to find out. They recruited 49 adults, aged between 52 and 91, and divided them into an experimental and control group. Both groups were first asked their subjective age—how old they felt as opposed to their chronological age—and tested for grip strength to establish a baseline. The experimental group was told they had done better than 80 percent of people their age. The control group received no feedback. After this experimental manipulation, both groups were tested again for grip strength and asked about how old they felt. The experimental group reported feeling, on average, younger than their baseline subjective age. No such change was seen in the control group. Also, the experimental group showed an increase in grip strength, while the grip strength of the control decreased somewhat.
These correlations do not necessarily mean that feeling young causes better health. Terracciano’s next step is to correlate subjective age with quantitative biological markers of age. While no study has yet been done to find associations between the newly developed epigenetic markers and subjective age, Terracciano is keen to see if there are strong correlations.
Still, the message seems to be that our chronological age really is just a number. “If people think that because they are getting older they cannot do things, or cut their social ties, or incorporate this negative view which limits their life, that can be really detrimental,” says Terracciano. “Fighting those negative attitudes, challenging yourself, keeping an open mind, being engaged socially, can absolutely have a positive impact.”
ANIL ANANTHASWAMY is an award-winning journalist and author. His first book, The Edge of Physics, was named Book of the Year in 2010 by PhysicsWorld. His second book, The Man Who Wasn’t There, was nominated for the PEN/E. O. Wilson Literary Science Writing Award. @AnilAnanth
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DUBLIN — Forensics experts say they have found a mass grave for young children at a former Catholic orphanage in Ireland where suspicions of unrecorded, unmarked burials have lingered for decades.
Friday’s announcement by the government-appointed Mother and Baby Homes Commission confirms a 2014 investigation by a local historian who found death certificates for nearly 800 children who died at the home in Tuam, County Galway, from its opening in 1925 to its 1961 closure.
The commission says excavations at the site from November to January found an underground structure divided into 20 chambers containing “significant quantities of human remains.”
It says DNA analysis of selected remains confirmed the ages of the dead ranged from 35 weeks to 3 years old and were buried when the orphanage was operating.
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