Posts Tagged ‘death’

2EQEGUFXTQI6RLSPFQKDTSLNPE
Walter Mischel in 2004. “If we have the skills to allow us to make discriminations about when we do or don’t do something,” Dr. Mischel said, “we are no longer victims of our desires.” (David Dini/Columbia University)

By Emily Langer

The experiment was “simplicity itself,” its creator, psychologist Walter Mischel, would later recall. The principal ingredient was a cookie or a pretzel stick or — most intriguingly to the popular imagination — a marshmallow.

In what became known as “the marshmallow test,” a child was placed in a room with a treat and presented with a choice. She could eat the treat right away. Or she could wait unaccompanied in the room, for up to 20 minutes, and then receive two treats in reward for her forbearance.

Conducting their work at a nursery school on the campus of Stanford University in the 1960s, Dr. Mischel and his colleagues observed responses that were as enlightening as they are enduringly adorable. Some children distracted themselves by putting their fingers in their ears or nose. At least one child caressed the marshmallow as he hungered for it. Only about 30 percent of the children managed to wait for the double reward.

Dr. Mischel, who continued his career at Columbia University and died Sept. 12 at 88, followed a cohort of the children for decades and presented his findings to mainstream readers in his 2014 book “The Marshmallow Test: Why Self-Control is the Engine of Success.”

His observations, widely noted and hotly debated, were striking: Children who had found ways to delay gratification, he found, had greater success in school, made more money and were less prone to obesity and drug addiction.

“What emerged from those studies is a different view of self-control, one that sees it as a matter of skill” and not a matter of “gritting your teeth,” said Yuichi Shoda, a professor of psychology at the University of Washington who worked with Dr. Mischel as a graduate student.

As worried parents conducted marshmallow tests at home, policymakers, educators and motivational speakers found a compelling catchphrase: “Don’t eat the marshmallow!” Even the ravenous Cookie Monster, a mainstay of the children’s TV show “Sesame Street,” was coaxed to resist a cookie.

Meanwhile, some psychologists challenged Dr. Mischel’s findings, arguing that a study group drawn from the privileged environs of Stanford could hardly yield reliable results. Skeptics noted that while affluent families might teach their children to delay gratification, in an effort to encourage financial and other forms of responsibility, children from disadvantaged homes learn that waiting to eat might mean not eating at all.

Dr. Mischel defended his research, emphasizing that in no way did he wish to suggest a laboratory performance — particularly by a preschooler — was destiny. The question, he said, is “how can you regulate yourself and control yourself in ways that make your life better?”

Walter Mischel was born Feb. 22, 1930, to a Jewish family in Vienna. His home was not far from that of Sigmund Freud, the founder of psychoanalysis. “Even as a young child I was aware of his presence,” Dr. Mischel once told the British Psychological Society, “and I suspect at some level I became quite interested in what makes people tick.”

Dr. Mischel’s family enjoyed a comfortable life until the rise of Nazism. His father, a businessman who had suffered from polio, was made to limp through the streets without his cane. Dr. Mischel recalled being humiliated by members of the Hitler Youth who tread on his new shoes. The experience, he told the Guardian, planted in him a desire to understand “the enabling conditions that allow people to go from being victims to being victors.”

After the Nazi annexation of Austria in 1938, the family fled the country and settled eventually in New York City, where they ran a five-and-dime store. Dr. Mischel, who became a U.S. citizen in the 1950s, helped support the family by working in an umbrella factory and as an elevator operator.

He was a 1951 psychology graduate of New York University and received a master’s degree from the City College of New York in 1953 and a PhD from Ohio State University in 1956, both in clinical psychology. He taught at Harvard University before settling at Stanford.

He said he became fascinated by the development of self-control in children by watching his daughters emerge from infancy into toddler-hood and girlhood.

“I began with a truly burning question,” he told the Guardian. “I wanted to know how my three young daughters developed, in a remarkably short period of time, from being howling, screaming, often impossible kids to people who were actually able to sit and do something that required them to concentrate. I wanted to understand this miraculous transformation.”

The subjects of the Stanford nursery-school tests were his daughters’ classmates. As the children grew up and he noticed correlations between their childhood self-control and future success, he decided to pursue the question more rigorously, through longitudinal study.

He conceded the limitations of his study group at Stanford. “It was an unbelievably elitist subset of the human race, which was one of the concerns that motivated me to study children in the South Bronx — kids in high-stress, poverty conditions,” he told the Atlantic in 2014, “and yet we saw many of the same phenomena as the marshmallow studies were revealing.”

Dr. Mischel proposed strategies for delaying gratification, such as putting the object at physical distance, by removing it from view, or at symbolic distance by imagining it to be something else. A marshmallow is not a sugary treat, for example, but rather a cotton ball.

In his own life, he reported success at resisting chocolate mousse by imagining the dessert to be covered in roaches. A self-described “three-packs-a-day smoker, supplemented by a pipe . . . supplemented by a cigar,” he said he conquered his addiction by recalling the image of a lung-cancer patient he had seen at Stanford, branded with X’s where he would be treated by radiation.

In addition to “The Marshmallow Test,” Dr. Mischel wrote and co-authored numerous texts on personality, child development and other fields of psychological research. He retired last year after more than three decades at Columbia.

His marriages to Frances Henry and Harriet Nerlove ended in divorce. Survivors include his partner of nearly two decades, Michele Myers of New York; three daughters from his second marriage, Judy Mischel of Chicago, Rebecca Mischel of Portland, Ore., and Linda Mischel Eisner of New York City; and six grandchildren.

Linda Mischel Eisner confirmed the death and said her father died at his home of pancreatic cancer.

Dr. Mischel professed to have found hope in his life’s work. “If we have the skills to allow us to make discriminations about when we do or don’t do something,” he told the New Yorker magazine, “we are no longer victims of our desires.”

“It’s not,” he said, “just about marshmallows.”

https://www.washingtonpost.com/local/obituaries/walter-mischel-psychologist-who-created-marshmallow-test-dies-at-88/2018/09/14/dcf24008-b782-11e8-94eb-3bd52dfe917b_story.html?utm_term=.bc74b74cf416

Advertisements

72OBCIFZ34I6RLNYAEJFIFWBAI
As a teenager during World War II, Freddie Oversteegen was one of only a few Dutch women to take up arms against the country’s Nazi occupiers. (Courtesy of National Hannie Schaft Foundation)

o
A recent image of Ms. Oversteegen. (Courtesy of National Hannie Schaft Foundation)

By Harrison Smith

She was 14 when she joined the Dutch resistance, though with her long, dark hair in braids she looked at least two years younger.

When she rode her bicycle down the streets of Haarlem in North Holland, firearms hidden in a basket, Nazi officials rarely stopped to question her. When she walked through the woods, serving as a lookout or seductively leading her SS target to a secluded place, there was little indication that she carried a handgun and was preparing an execution.

The Dutch resistance was widely believed to be a man’s effort in a man’s war. If women were involved, the thinking went, they were likely doing little more than handing out anti-German pamphlets or newspapers.

Yet Freddie Oversteegen and her sister Truus, two years her senior, were rare exceptions — a pair of teenage women who took up arms against Nazi occupiers and Dutch “traitors” on the outskirts of Amsterdam. With Hannie Schaft, a onetime law student with fiery red hair, they sabotaged bridges and rail lines with dynamite, shot Nazis while riding their bikes, and donned disguises to smuggle Jewish children across the country and sometimes out of concentration camps.

In perhaps their most daring act, they seduced their targets in taverns or bars, asked if they wanted to “go for a stroll” in the forest — and “liquidated” them, as Ms. Oversteegen put it, with a pull of the trigger.

“We had to do it,” she told one interviewer. “It was a necessary evil, killing those who betrayed the good people.” When asked how many people she had killed or helped kill, she demurred: “One should not ask a soldier any of that.”

Freddie Oversteegen, the last remaining member of the Netherlands’ most famous female resistance cell, died Sept. 5, one day before her 93rd birthday. She was living in a nursing home in Driehuis, five miles from Haarlem, and had suffered several heart attacks in recent years, said Jeroen Pliester, chairman of the National Hannie Schaft Foundation.

The organization was founded by Ms. Oversteegen’s sister in 1996 to promote the legacy of Schaft, who was captured and executed by the Nazis weeks before the end of World War II. “Schaft became the national icon of female resistance,” Pliester said, a martyr whose story was taught to schoolchildren across the Netherlands and memorialized in a 1981 movie, “The Girl With the Red Hair,” which took its title from her nickname.

Ms. Oversteegen served as a board member in her sister’s organization. But she “decided to be a little bit out of the limelight,” Pliester said, and was sometimes overshadowed by Schaft and Truus, the group’s leader.

“I have always been a little jealous of her because she got so much attention after the war,” Ms. Oversteegen told Vice Netherlands in 2016, referring to her sister. “But then I’d just think, ‘I was in the resistance as well.’ ”

It was, she said, a source of pride and of pain — a five-year experience that she never regretted, but that came to haunt her in peacetime. Late at night, unable to fall asleep, she sometimes recalled the words of an old battle song that served as an anthem for her and her sister: “We have carried the best to their graves/ torn and fired at, beaten till the blood ran/ surrounded by the executioners on the scaffold and jail/ but the raging of the enemy doesn’t frighten us.”

Freddie Nanda Oversteegen was born in the village of Schoten, now part of Haarlem, on Sept. 6, 1925. Her parents divorced when she was a child, and Freddie and Truus were raised primarily by their mother, a communist who instilled a sense of social responsibility in the young girls; she eventually remarried and had a son.

In interviews with anthropologist Ellis Jonker, collected in the 2014 book “Under Fire: Women and World War II,” Freddie Oversteegen recalled that their mother encouraged them to make dolls for children suffering in the Spanish Civil War, and beginning in the early 1930s volunteered with International Red Aid, a kind of communist Red Cross for political prisoners around the world.

Although living in poverty, sleeping on makeshift mattresses stuffed with straw, the family harbored refugees from Germany and Amsterdam, including a Jewish couple and a mother and son who lived in their attic. After German forces invaded the Netherlands in May 1940, the couples were moved to another location; Jewish community leaders feared a potential raid, because of the family’s well-known political leanings.

“They were all deported and murdered,” Ms. Oversteegen told Jonker. “We never heard from them again. It still moves me dreadfully, whenever I talk about it.”

Ms. Oversteegen and her sister began their resistance careers by distributing pamphlets (“The Netherlands have to be free!”) and hanging anti-Nazi posters (“For every Dutch man working in Germany, a German man will go to the front!”). Their efforts apparently attracted the attention of Frans van der Wiel, commander of the underground Haarlem Council of Resistance, who invited them to join his team — with their mother’s permission.

“Only later did he tell us what we’d actually have to do: sabotage bridges and railway lines,” Truus Oversteegen said, according to Jonker. “We told him we’d like to do that. ‘And learn to shoot, to shoot Nazis,’ he added. I remember my sister saying, ‘Well, that’s something I’ve never done before!’ ”

By Truus’s account, it was Freddie Oversteegen who became the first to shoot and kill someone. “It was tragic and very difficult and we cried about it afterwards,” Truus said. “We did not feel it suited us — it never suits anybody, unless they are real criminals. . . . One loses everything. It poisons the beautiful things in life.”

The Oversteegen sisters were officially part of a seven-person resistance cell, which grew to include an eighth member, Schaft, after she joined in 1943. But the three girls worked primarily as a stand-alone unit, Pliester said, acting on instructions from the Council of Resistance.

After the war ended in 1945, Truus worked as an artist, making paintings and sculptures inspired by her years with the resistance, and wrote a popular memoir, “Not Then, Not Now, Not Ever.” She died in 2016, two years after Prime Minister Mark Rutte awarded the sisters the Mobilization War Cross, a military honor for service in World War II.

For her part, Freddie Oversteegen told Vice that she coped with the traumas of the war “by getting married and having babies.” She married Jan Dekker, taking the name Freddie Dekker-Oversteegen, and raised three children. They survive her, as do her half brother and four grandchildren. Her husband, who worked at the steel company Hoogovens, is deceased.

In interviews, Ms. Oversteegen often spoke of the physics of killing — not the feel of the trigger or kick of the gun, but the inevitable collapse that followed, her victims’ fall to the ground.

“Yes,” she told one interviewer, according to the Dutch newspaper IJmuider Courant , “I’ve shot a gun myself and I’ve seen them fall. And what is inside us at such a moment? You want to help them get up.”

https://www.washingtonpost.com/local/obituaries/freddie-oversteegen-dutch-resistance-fighter-who-killed-nazis-through-seduction-dies-at-92/2018/09/16/7876eade-b9b7-11e8-a8aa-860695e7f3fc_story.html?noredirect=on&utm_term=.dc5eb2caed7f

Near-death experiences, or NDEs, are significant psychological events that occur close to actual or perceived impending death. Commonly reported aspects of NDEs include out of body experiences, feelings of transitioning to another world and of inner peace, many of which are also reported by users taking DMT.

DMT is a potent psychedelic found in certain plants and animals, and is the major psychoactive compound in ayahuasca, the psychedelic brew prepared from vines and used in ceremonies in south and central America.

Researchers from Imperial College London set out to look at the similarities between the DMT experience and reports of NDEs. Their findings, published today in the journal Frontiers in Psychology, reveal a large overlap between those who have had NDEs and healthy volunteers administered DMT.

As part of the trial, the team looked at 13 healthy volunteers over two sessions, who were given intravenous DMT and placebo, receiving one of four doses of the compound. The research was carried out at the NIHR Imperial Clinical Research Facility. All volunteers were screened and overseen by medical staff throughout.

Researchers compared the participants’ experiences against a sample of 67 people who had previously reported actual NDEs and who had completed a standardised questionnaire to try and quantify their experiences. The group were asked a total of 16 questions including ‘Did scenes from your past come back to you?’ and ‘Did you see, or feel surrounded by, a brilliant light?’.

Following each dosing session, the 13 healthy volunteers filled out exactly the same questionnaire to find out what sort of experiences they had whilst on DMT and how this compared to the NDE group.

The team found that all volunteers scored above a given threshold for determining an NDE, showing that DMT could indeed mimic actual near death experiences and to a comparable intensity as those who have actually had an NDE.

Dr Robin Carhart-Harris, who leads the Psychedelic Research Group at Imperial and supervised the study, said: “These findings are important as they remind us that NDE occur because of significant changes in the way the brain is working, not because of something beyond the brain. DMT is a remarkable tool that can enable us to study and thus better understand the psychology and biology of dying.”

Professor David Nutt, Edmond J Safra Chair in Neuropsychopharmacology at Imperial, said: “These data suggest that the well-recognised life-changing effects of both DMT and NDE might have the same neuroscientific basis.”

PhD candidate Chris Timmermann, a member of the Psychedelic Research Group at Imperial and first author of the study, said: “Our findings show a striking similarity between the types of experiences people are having when they take DMT and people who have reported a near-death experience.”

The researchers note some subtle, but important differences between DMT and NDE responses, however. DMT was more likely to be associated with feelings of ‘entering an unearthly realm’, whereas actual NDEs brought stronger feelings of ‘coming to a point of no return’. The team explain that this may be down to context, with volunteers being screened, undergoing psychological preparation beforehand and being monitored through in a ‘safe’ environment.

“Emotions and context are particularly important in near-death experiences and with psychedelic substances,” explains Timmermann. “While there may be some overlap between NDE and DMT-induced experiences, the contexts in which they occur are very different.”

“DMT is a potent psychedelic and it may be that it is able to alter brain activity in a similar fashion as when NDEs occur.”

“We hope to conduct further studies to measure the changes in brain activity that occur when people have taken the compound. This, together with other work, will help us to explore not only the effects on the brain, but whether they might possibly be of medicinal benefit in future.”

https://www.technologynetworks.com/neuroscience/news/powerful-psychedelic-compound-models-near-death-experiences-in-the-brain-307638?utm_campaign=NEWSLETTER_TN_Neuroscience_2017&utm_source=hs_email&utm_medium=email&utm_content=65211042&_hsenc=p2ANqtz-_szeHBJKSgWgl_SDBvWrV8ncLN5bzJ6mkDQpNXKHOwtLpcxo_Vp3gC6mytMbuTKLxvvbahYFeA9RFa28pxLHQs18Nimg&_hsmi=65211042

By Ayana Archie and Jay Croft

A female orca whale is still apparently grieving her dead calf and still swimming with its body after more than two weeks, authorities say.

“It’s heartbreaking to watch,” said Michael Milstein of the National Oceanic and Atmospheric Administration’s West Coast Region. “This kind of behavior is like a period of mourning and has been seen before. What’s extraordinary about this is the length of time.”

The adult — Tahlequah, or J35 as the whale has come to be known by researchers — and corpse were last seen definitively Thursday afternoon, 17 days after the baby’s birth. The female calf died after a few hours.

The mother, preventing the body from sinking to the ocean floor, has been carrying it and nudging it toward the surface of the Pacific off the coast of Canada and the northwestern US.
Orcas, also called killer whales, are highly social, and this pod was spotted Friday afternoon near Vancouver, British Columbia.

Another struggling female in the same pod — J50, also known as Scarlet — was shot with antibiotics to fight an infection, since scientists worry that she has been losing a frightening amount of weight.

These are grim signs. The Southern Resident population the females belong to has about 75 members, and has not had a successful birth in three years. In the last 20 years, only 25% of the babies have survived.

‘Deep feelings’ not uncommon

Scientists says grieving is common among mammals such as whales, dolphins, elephants and deer. Evidence shows the orca brain is large, complex and highly developed in areas dealing with emotions, said Lori Marino, president of the Whale Sanctuary Project.

“It’s not surprising they’re capable of deep feelings, and that’s what (Tahlequah) is showing,” Marino said. “What exactly she’s feeling we’ll never know. But the bonds between mothers and calves are extremely strong. Everything we know about them says this is grieving.”

Center for Whale Research founder Ken Balcomb said it’s “unprecedented” for an orca to keep this going for so long. He said the mother has traveled more than 1,000 miles with the corpse, which has begun to decompose.

“It is a grief, a genuine mourning,” he said.

Dwindling food source

The problem for this group of killer whales is a dwindling food supply, scientists say. Most killer whales eat a wider diet, but this particular group of about 75 resident orcas eats just salmon, which have been overfished in the area for commercial consumption. Manmade contraptions, like hydroelectric power sources, block the salmons’ path to release eggs.

Exacerbating the problem is that orcas do not have babies often or in large numbers, and when they do, it is a long process. It takes a calf a little under a year and a half to fully develop in the womb, and they nurse for another year. They must learn to swim right away, Balcomb said, and rely on their mothers for food for several years — first through nursing, then through providing fish.

“Extinction is looming,” Balcomb told CNN last month, but it is not inevitable if humans restore salmon populations and river systems in time.

https://www.cnn.com/2018/08/10/us/orca-whale-still-carrying-dead-baby-trnd/index.html

Suicide rates and temperatures are both on the rise, but are these two occurrences connected? A new study suggests maybe so. The research revealed hotter-than-average months corresponded to more deaths by suicide—and the effect isn’t limited to the summer, even warmer winters show the trend.

In the study, published in Nature Climate Change, the investigators looked at all of the suicides that occurred in the U.S. and Mexico over several decades (1968 to 2004 for the U.S. and 1990 to 2010 for Mexico), comprising 851,088 and 611,366 deaths, respectively. They then observed how monthly temperature fluctuations over these periods in every county or municipality in both countries correlated to the suicide rates for that region. They discovered that for every 1-degree Celsius (1.8-degree Fahrenheit) rise in temperature, there was a 0.7 percent increase in suicide rates in the U.S. and a 2.1 percent increase in Mexico, averaging a 1.4 percent increment across both countries. That is, over the years, a given county would see more deaths by suicide in warmer-than-average months.

Notably, the average temperature of the county did not matter; for example, Dallas and Minneapolis saw a similar rise in suicide rates. The effect did not depend on the month either—it made no difference whether it was January or July. There was also no difference between gender, socioeconomic status, access to guns, air-conditioning and whether it was an urban or rural region. Across the board, when temperatures rose in a given place, so did the number of suicides.

“A lot of times when you hear about climate change and climate change impacts, you hear this catch phrase ‘climate change is going to generate winners and losers,’” says study author Marshall Burke. “Some people could benefit from climate change, the idea being if you live in a really cold location, sometimes things improve when you warm it up a little bit. We do not find that for suicide.” He continues, “Climate change in terms of suicide is not going to generate winners and losers, it’s just going to generate losers. Everyone, as far as we can tell—no matter whether you live in a cold place or live in a hot place—everyone is going to be harmed in terms of suicide risk when we increase the temperature.”

If climate change continues on its current trajectory with an estimated temperature increase of 2.5 degrees C (4.5 degrees F) by 2050, Burke, who is an assistant professor of earth system science at Stanford University, projects suicide rates would rise by 1.85 percent, resulting in an additional 21,770 deaths by suicide across the U.S. and Mexico. For comparison, economic recession is thought to increase suicide rates by 0.8 percent whereas news of celebrity suicides accounts for a 4.6 percent bump in rates.

Not everyone is convinced by these projections, though. Jill Harkavy-Friedman, vice president of research at the American Foundation for Suicide Prevention, says, “I think it’s an interesting and provocative idea. These two things may be co-occurring. You know, it’s possible that the rate of suicide is going up as the temperature is going up. But we don’t know that there’s anything causal about that.”

In their study the researchers speculate there could be some biological effect linked to temperature regulation in the brain that alters mental health and could underlie the correlation. In an attempt to connect mental well-being with temperature change more generally, they examined more than 600 million Twitter posts for depressive language over a 14-month period. The researchers again found hotter months corresponded to a higher probability of using depressive language. Prior work by the researchers also saw a similar trend in interpersonal conflict, with a 4 percent rise in violence attributed to climate change.

Burke acknowledged suicide is a complex phenomenon and temperature is certainly not the only or even the most important factor affecting mental health: “What studies like ours contribute is just saying on average, as you increase temperature, what’s going to happen to suicide rates? So that won’t tell you with utmost certainty what’s going to happen in specific locations, but it will tell you okay on average this is what we should expect. Our view is it would be foolhardy to ignore the evidence,” he notes.

Radley Horton, an associate research professor at Columbia University who was not involved in the research, says the study is a good reminder of how fundamental temperature is and how widespread its impacts are. “The deeper we look, the more likely we are to uncover ways that temperature directly impacts things we care about,” he says. “Climate uncertainty is not our friend. The further we push things, the greater the risk.”

https://www.scientificamerican.com/article/global-warming-linked-to-higher-suicide-rates-across-north-america/

by Elie Dolgin

There might be no natural limit to how long humans can live — at least not one yet in sight — contrary to the claims of some demographers and biologists.

That’s according to a statistical analysis published Thursday in Science1 on the survival probabilities of nearly 4,000 ‘super-elderly’ people in Italy, all aged 105 and older.

A team led by Sapienza University demographer Elisabetta Barbi and University of Roma Tre statistician Francesco Lagona, both based in Rome, found that the risk of death — which, throughout most of life, seems to increase as people age — levels off after age 105, creating a ‘mortality plateau’. At that point, the researchers say, the odds of someone dying from one birthday to the next are roughly 50:50 (see ‘Longevity unlimited’).

“If there is a mortality plateau, then there is no limit to human longevity,” says Jean-Marie Robine, a demographer at the French Institute of Health and Medical Research in Montpellier, who was not involved in the study.

That would mean that someone like Chiyo Miyako, the Japanese great-great-great-grandmother who, at 117, is the world’s oldest known person, could live for years to come — or even forever, at least hypothetically.

Researchers have long debated whether humans have an upper age limit. The consensus holds that the risk of death steadily increases in adulthood, up to about age 80 or so. But there’s vehement disagreement about what happens as people enter their 90s and 100s.

Some scientists have examined demographic data and concluded that there is a fixed, natural ‘shelf-life’ for our species and that mortality rates keep increasing. Others have looked at the same data and concluded that the death risk flattens out in one’s ultra-golden years, and therefore that human lifespan does not have an upper threshold.

Age rage

In 2016, geneticist Jan Vijg and his colleagues at Albert Einstein College of Medicine in New York City rekindled the debate when they analysed the reported ages at death for the world’s oldest individuals over a half-century. They estimated that human longevity hit a ceiling at about 115 years — 125 tops.

Vijg and his team argued2 that with few, if any, gains in maximum lifespan since the mid-1990s, human ageing had reached its natural limit. The longest known lifespan belongs to Jeanne Calment, a French super-centenarian who died in 1997 at age 122.

Experts challenged the statistical methods in the 2016 study, setting off a firestorm into which now step Barbi and Lagona. Working with colleagues at the Italian National Institute of Statistics, the researchers collected records on every Italian aged 105 years and older between 2009 and 2015 — gathering certificates of death, birth and survival in an effort to minimize the chances of ‘age exaggeration’, a common problem among the oldest old.

They also tracked individual survival trajectories from one year to the next, rather than lump people into age intervals as previous studies that combine data sets have done. And by focusing just on Italy, which has one of the highest rates of centenarians per capita in the world, they avoided the issue of variation in data collection among different jurisdictions.

As such, says Kenneth Howse, a health-policy researcher at the Oxford Institute of Population Ageing in the United Kingdom, “these data provide the best evidence to date of extreme-age mortality plateaus in humans”.

Ken Wachter, a mathematical demographer at the University of California, Berkeley, and an author of the latest study, suspects that prior disputes over the patterns of late-life mortality have largely stemmed from bad records and statistics. “We have the advantage of better data,” he says. “If we can get data of this quality for other countries, I expect we’re going to see much the same pattern.”

Robine is not so sure. He says that unpublished data from France, Japan and Canada suggest that evidence for a mortality plateau is “not as clear cut”. A global analysis is still needed to determine whether the findings from Italy reflect a universal feature of human ageing, he says.

Off limits

The world is home to around 500,000 people aged 100 and up — a number that’s predicted to nearly double with each coming decade. Even if the risk of late-life mortality remains constant at 50:50, the swelling global membership in the 100-plus club should translate into a creep upwards in the oldest person alive by about one year per decade, says Joop de Beer, a longevity researcher at the Netherlands Interdisciplinary Demographic Institute in The Hague.

Many researchers say they hope to better understand what’s behind the levelling off of mortality rates in later life. Siegfried Hekimi, a geneticist at McGill University in Montreal, Canada, speculates that the body’s cells eventually reach a point where repair mechanisms can offset further damage to keep mortality rates level.

“Why this plateaus out and what it means about the process of ageing — I don’t think we have any idea,” Hekimi says.

For James Kirkland, a geriatrician at the Mayo Clinic in Rochester, Minnesota, the strong evidence for a mortality plateau points to the possibility of forestalling death at any age. Some experts think that the very frail are beyond repair. But if the odds of dying don’t increase over time, he says, interventions that slow ageing are likely to make a difference, even in the extremely old.

Not everyone buys that argument — or the conclusions of the latest paper.

Brandon Milholland, a co-author of the 2016 Nature paper, says that the evidence for a mortality plateau is “marginal”, as the study included fewer than 100 people who lived to 110 or beyond. Leonid Gavrilov, a longevity researcher at the University of Chicago in Illinois, notes that even small inaccuracies in the Italian longevity records could lead to a spurious conclusion.

Others say the conclusions of the study are biologically implausible. “You run into basic limitations imposed by body design,” says Jay Olshansky, a bio-demographer at the University of Illinois at Chicago, noting that cells that do not replicate, such as neurons, will continue to wither and die as a person ages, placing upper boundaries on humans’ natural lifespan.

This study is thus unlikely to be the last word on the age-limit dispute, says Haim Cohen, a molecular biologist at Bar-Ilan University in Ramat-Gan, Israel. “I’m sure that the debate is going to continue.”


Jan Carette and his colleagues have discovered a “death code” that unleashes a type of cell death.

Dying cells generally have two options: go quietly, or go out with a bang.

The latter, while more conspicuous, is also mechanistically more mysterious. Now, scientists at the Stanford University School of Medicine have pinpointed what they believe is the molecular “code” that unleashes this more violent variety of cell death.

This particular version of cell suicide is called necroptosis, and it typically occurs as a result of some sort of infection or pathogenic invader. “Necroptosis is sort of like the cell’s version of ‘taking one for the team,’” said Jan Carette, PhD, assistant professor of microbiology and immunology. “As the cell dies, it releases its contents, including a damage signal that lets other cells know there’s a problem.”

Seen in this light, necroptosis seems almost altruistic, but the process is also a key contributor to autoimmune diseases; it’s even been implicated in the spread of cancer.

In a new study, Carette and his collaborators discovered the final step of necroptosis, the linchpin upon which the entire process depends. They call it “the death code.”

Their work, which was published online June 7 in Molecular Cell, not only clears up what happens during this type of cell death, but also opens the door to potential new treatments for diseases in which necroptosis plays a key role, such as inflammatory bowel disease and multiple sclerosis. Carette is the senior author, and postdoctoral scholar Cole Dovey, PhD, is the lead author.

Initiating detonation

When a cell’s health is threatened by an invader, such as a virus, a cascade of molecular switches and triggers readies the cell for death by necroptosis. Until recently, scientists thought they had traced the pathway down to the last step. But it turns out that the entire chain is rendered futile without one special molecule, called inositol hexakisphosphate, or IP6, which is part of a larger collection of molecules known as inositol phosphates. Carette likens IP6 to an access code; only in this case, when the code is punched in, it’s not a safe or a cellphone that’s unlocked: It’s cell death. Specifically, a protein called MLKL, which Carette has nicknamed “the executioner protein,” is unlocked.

“This was a big surprise. We didn’t know that the killer protein required a code, and now we find that it does,” Dovey said. “It’s held in check by a code, and it’s released by a code. So only when the code is correct does the killer activate, puncturing holes in the cell’s membrane as it prepares to burst the cell open.”

MLKL resides inside the cell, which may seem like an error on evolution’s part; why plant an explosive in life’s inner sanctum? But MLKL is tightly regulated, and it requires multiple green lights before it’s cleared to pulverize. Even if all other proteins and signaling molecules prepare MLKL for destruction, IP6 has the final say. If IP6 doesn’t bind, MLKL remains harmless, like a cotton ball floating inside the cell.

When it’s not killing cells, MLKL exists as multiple units, separate from one another. But when IP6 binds to one of these units, the protein gathers itself up into one functional complex. Only then, as a whole, is MLKL a full-fledged killer. It’s like a grenade split into its component parts. None of them are functional on their own. But put back together, the tiny bomb is ready to inflict damage.

“We’ve come to realize that, after the cell explodes, there are these ‘alarm’ molecules that alert the immune system,” Dovey said. “When the cell releases its contents, other cells pick up on these cautionary molecules and can either shore up defenses or prepare for necroptosis themselves.”

Screening for the Grim Reaper

In their quest to understand exactly how necroptosis occurs, Carette and Dovey performed an unbiased genetic screen, in which they scoured the entire genome for genes that seemed to be particularly critical toward the end of the pathway, where they knew MLKL took action. Before the IP6 finding, it was known that an intricate pathway impinged on MLKL. But only through this special genetic screen, in which they systematically tested the function of every gene at this end stage, were they able to see that IP6 was the key to necroptosis.

“Genetic screens are a lot of fun because you never know what you’re going to get,” Carette said. “We feel quite excited that we’ve been able to pinpoint IP6.”

Their screen revealed that IP6 binds with especially high specificity. Other similar versions of inositol phosphate, such as IP3, didn’t pass muster, and when bound to MLKL had no effect. This gave Carette an interesting idea. For conditions like irritable bowel disease, in which erroneous necroptosis contributes to the severity of the disease, it would be desirable to disable IP6 from binding under those conditions. Perhaps blocking the binding site, or tricking MLKL into binding to one of the other versions of inositol phosphate, could do the trick. Either way, Carette and his collaborators are now digging further into the structure of IP6 bound to MLKL to better understand exactly how the killer is unleashed.

“In terms of drug discovery, inositol phosphates have been somewhat ignored, so we’re really excited to be able to look into these small molecules for potential therapeutic reasons,” Carette said.

https://www.technologynetworks.com/cell-science/news/cellular-death-code-identified-304850?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=63609833&_hsenc=p2ANqtz-9qdyzMcEm3q0J6mlEARWf6NhG5b_3NFqLfwxNaoJ8n6Y4bATQcn5d8BjpMNJZ4EFWXploBzGufQZD5OhVtNnjSDPtCtQ&_hsmi=63609833