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Aging, or senescent cells, which stop dividing but don’t die, can accumulate in the body over the years and fuel chronic inflammation that contributes to conditions such as cancer and degenerative disorders. In mice, eliminating senescent cells from aging tissues can restore tissue balance and lead to an increased healthy lifespan. Now a team led by investigators at Massachusetts General Hospital (MGH) has found that the immune response to a virus that is ubiquitously present in human tissues can detect and eliminate senescent cells in the skin. For the study, which is published in Cell, the scientists analyzed young and old human skin samples to learn more about the clearance of senescent cells in human tissue. The researchers found more senescent cells in the old skin compared with young skin samples. However, in the samples from old individuals, the number of senescent cells did not increase as individuals got progressively older, suggesting that some type of mechanism kicks in to keep them in check. Experiments suggested that once a person becomes elderly, certain immune cells called killer CD4+ T cells are responsible for keeping senescent cells from increasing. Indeed, higher numbers of killer CD4+ T cells in tissue samples were associated with reduced numbers of senescent cells in old skin. When they assessed how killer CD4+ T cells keep senescent cells in check, the researchers found that aging skin cells express a protein, or antigen, produced by human cytomegalovirus, a pervasive herpesvirus that establishes lifelong latent infection in most humans without any symptoms. By expressing this protein, senescent cells become targets for attack by killer CD4+ T cells. “Our study has revealed that immune responses to human cytomegalovirus contribute to maintaining the balance of aging organs,” says senior author Shawn Demehri, MD, PhD, director of the High Risk Skin Cancer Clinic at MGH and an associate professor of Dermatology at Harvard Medical School. “Most of us are infected with human cytomegalovirus, and our immune system has evolved to eliminate cells, including senescent cells, that upregulate the expression of cytomegalovirus antigens.” These findings, which highlight a beneficial function of viruses living in our body, could have a variety of clinical applications. “Our research enables a new therapeutic approach to eliminate aging cells by boosting the anti-viral immune response,” says Demehri. “We are interested in utilizing the immune response to cytomegalovirus as a therapy to eliminate senescent cells in diseases like cancer, fibrosis and degenerative diseases.” Demehri notes that the work may also lead to advances in cosmetic dermatology, for example in the development of new treatments to make skin look younger.
Via Juan Lama
Over the last few decades, life expectancy has increased dramatically around the globe. The average person born in 1960, the earliest year the United Nations began keeping global data, could expect to live to 52.5 years of age. Today, the average is 72. In the UK, where records have been kept longer, this trend is even greater. In 1841, a baby girl was expected to live to just 42 years of age, a boy to 40. In 2016, a baby girl could expect to reach 83; a boy, 79. The natural conclusion is that both the miracles of modern medicine and public health initiatives have helped us live longer than ever before – so much so that we may, in fact, be running out of innovations to extend life further. In September 2018, the Office for National Statistics confirmed that, in the UK at least, life expectancy has stopped increasing. Beyond the UK, these gains are slowing worldwide. This belief that our species may have reached the peak of longevity is also reinforced by some myths about our ancestors: it’s common belief that ancient Greeks or Romans would have been flabbergasted to see anyone above the age of 50 or 60, for example. In fact, while medical advancements have improved many aspects of healthcare, the assumption that human life span has increased dramatically over centuries or millennia is misleading. Overall life expectancy, which is the statistic reflected in reports like those above, hasn’t increased so much because we’re living far longer than we used to as a species. It’s increased because more of us, as individuals, are making it that far.
“There is a basic distinction between life expectancy and life span,” says Stanford University historian Walter Scheidel, a leading scholar of ancient Roman demography. “The life span of humans – opposed to life expectancy, which is a statistical construct – hasn’t really changed much at all, as far as I can tell.”
Life expectancy is an average. If you have two children, and one dies before their first birthday but the other lives to the age of 70, their average life expectancy is 35. That’s mathematically correct – and it certainly tells us something about the circumstances in which the children were raised. But it doesn’t give us the full picture. It also becomes especially problematic when looking at eras, or in regions, where there are high levels of infant mortality. Most of human history has been blighted by poor survival rates among children, and that continues in various countries today. This averaging-out, however, is why it’s commonly said that ancient Greeks and Romans, for example, lived to just 30 or 35. But was that really the case for people who survived the fragile period of childhood, and did it mean that a 35-year-old was truly considered ‘old’? If one’s thirties were a decrepit old age, ancient writers and politicians don’t seem to have got the message. In the early 7th Century BC, the Greek poet Hesiod wrote that a man should marry “when you are not much less than 30, and not much more”. Meanwhile, ancient Rome’s ‘cursus honorum’ – the sequence of political offices that an ambitious young man would undertake – didn’t even allow a young man to stand for his first office, that of quaestor, until the age of 30 (under Emperor Augustus, this was later lowered to 25; Augustus himself died at 75). To be consul, you had to be 43 – eight years older than the US’s minimum age limit of 35 to hold a presidency. In the 1st Century, Pliny devoted an entire chapter of The Natural History to people who lived longest. Among them he lists the consul M Valerius Corvinos (100 years), Cicero’s wife Terentia (103), a woman named Clodia (115 – and who had 15 children along the way), and the actress Lucceia who performed on stage at 100 years old.
A new study by EPFL researchers shows how RNA species called TERRA muster at the tip of chromosomes, where they help to prevent telomere shortening and premature cell aging. Molecules that accumulate at the tip of chromosomes are known to play a key role in preventing damage to our DNA. Now, researchers at EPFL have unraveled how these molecules home in on specific sections of chromosomes—a finding that could help to better understand the processes that regulate cell survival in aging and cancer. Much like an aglet of a shoelace prevents the end of the lace from fraying, stretches of DNA called telomeres form protective caps at the ends of chromosomes. But as cells divide, telomeres become shorter, making the protective cap less effective. Once telomeres get too short, the cell stops dividing. Telomere shortening and malfunction have been linked to cell aging and age-related diseases, including cancer. Scientists have known that RNA species called TERRA help to regulate the length and function of telomeres. Discovered in 2007 by postdoc Claus Azzalin in the team of EPFL Professor Joachim Lingner, TERRA belongs to a class of molecules called noncoding RNAs, which are not translated into proteins but function as structural components of chromosomes. TERRA accumulates at chromosome ends, signaling that telomeres should be elongated or repaired. However, it was unclear how TERRA got to the tip of chromosomes and remained there. “The telomere makes up only a tiny bit of the total chromosomal DNA, so the question is ‘how does this RNA find its home?’”, Lingner says. To address this question, postdoc Marianna Feretzaki and others in the teams of Joachim Lingner at EPFL and Lumir Krejci at Masaryk University set out to analyze the mechanism through which TERRA accumulates at telomeres, as well as the proteins involved in this process. The findings are published in Nature.
A new study from the University of Eastern Finland shows that a moderately high intake of dietary cholesterol or consumption of up to one egg per day is not associated with an elevated risk of stroke. Furthermore, no association was found in carriers of the apolipoprotein E phenotype 4 (APOE4), which affects cholesterol metabolism and is remarkably common among the Finnish population. The findings were published in theAmerican Journal of Clinical Nutrition. Findings from earlier studies addressing the association of dietary cholesterol or egg intake with the risk of stroke have been contradictory. Some studies have found an association between high dietary cholesterol intake and an increased risk of stroke, while others have associated the consumption of eggs, which are high in cholesterol, with a reduced risk of stroke. For most people, dietary cholesterol plays a very small role in affecting their serum cholesterol levels. However, in carriers of APOE4 -- which significantly impacts cholesterol metabolism -- the effect of dietary cholesterol on serum cholesterol levels is greater. In Finland, the prevalence of APOE4, which is a hereditary variant, is exceptionally high, with approximately one third of the population presenting as carriers. Yet, research data on the association between a high intake of dietary cholesterol and the risk of stroke in this population group has not been available until now. The dietary habits of 1,950 men aged between 42 and 60 years with no baseline diagnosis of a cardiovascular disease were assessed at the onset the Kuopio Ischaemic Heart Disease Risk Factor Study, KIHD, in 1984-1989 at the University of Eastern Finland. APOE phenotype data were available for 1,015 of the men participating in the study. Of those, 32% were known carriers of APOE4. During a follow-up of 21 years, 217 men were diagnosed with stroke. The study found that neither dietary cholesterol nor egg consumption was associated with the risk of stroke -- not even in carriers of APOE4.
Men in the Top 1% can expect to live until age 87.3, nearly 15 years longer than those in the Bottom 1%, according to research by Stanford economics professor Raj Chetty and seven co-authors. America's wealthiest men live longer than their counterparts in any other country, while the poorest have life expectancies comparable to men in Sudan and Pakistan. The richest women, meanwhile, have life expectancies just shy of 89 years, a full decade longer than the poorest women.
Elephants’ genomes possess 20 copies of a tumor suppressing gene called P53, new research shows.
A longstanding mystery in biology is why the rate of cancer incidence in a species does not scale up with body size and longevity. Take elephants for instance, which live to approximately the same age as humans and have 100 times more cells, yet hardly ever develop cancer, a disease which is estimated to affect 40 percent of Americans at some point in their lives.
ou'd expect elephants would have higher rates of cancer, because elephants have significantly more cells than humans and more cells means more opportunities for cancerous mutations to occur. The fact that this isn’t the case gives rise to the conundrum known as Peto’s Paradox, the resolution of which may provide valuable insight into preventing cancer in humans.
Recently a team of geneticists led by Joshua Schiffman at the University of Utah made major headway in this direction when they studied the cells of Asian and African elephants from the San Diego Frozen Zoo and found that elephants’ genomes possessed 20 copies of a tumor suppressing gene called P53.
For the sake of comparison, the team looked at the genomes of more than 60 other species (including humans) and found that most only possess a single copy of this gene, suggesting that this redundancy in the elephant genome may finally explain the low rate of cancer in the species. The results of the study were published today in an editorial for the Journal of the American Medical Association.
“If you’re interested in cancer the first gene to look at is P53, it is the master tumor suppressor,” said Vincent Lynch, a human geneticist at the University of Chicago who published supporting research in a preprint study on Biorxiv. “We thought maybe elephants have another copy, but certainly not 19 more copies than other animals. This discovery is a big deal.”
According to Lynch, the canonical copy of the P53 gene along with the 19 retrogene copies make elephants more sensitive to DNA damage during cell replication. This hypersensitivity to genetic anomalies means that cells are quicker to ‘commit suicide’ when they are found to be damaged, halting the proliferation of potentially cancerous cells before it begins.
While multiple copies of the P53 gene might seem like a wholly positive evolutionary development, the overexpression of this gene likely comes with some tradeoffs, such as reproductive senescence or rapid aging.
“There is definitely a tradeoff, or else many other species would have evolved duplicate P53 genes by now,” said Lynch. “We don’t know what the tradeoff was, but elephants either found a way to deal with it or broke whatever constraint prevented organisms from evolving many P53 copies.”
There might be a way to stave off the memory loss people experience as they get older. As people age, a protein that disrupts brain cell repair gradually builds up in the blood and cerebrospinal fluid. The offending protein, called beta2-microglobulin (B2M), has now been shown to affect how mice perform in memory tests. Work is already under way to identify drugs that mop up or destroy B2M which will allow the researchers to test if the same applies to humans. If so, the same drug could offer a solution.
"Right now, the idea is to develop antibodies or small molecules that can either block the effects of the protein or help to remove it from old blood," says Saul Villeda of the University of California at San Francisco. Villeda's discovery is the first detailed investigation of a so-called "anti-elixir" factor, in other words one that builds up with age and causes brain degeneration. Most research aimed at reversing ageing so far has focused on "elixir" factors – agents that bring back lost youth. For example, when the the blood of young mice is injected into old mice, it halts brain and muscle degeneration, helps fractured bones heal and prevents heart damage.
B2M's main job is to help the immune system tell the difference between foreign cells and those from the body, but it also plays a role in development of the nervous system. When Villeda's team injected B2M into the brains or blood of young mice, they performed almost as badly as elderly mice on two kinds of memory test. When the molecule had been naturally eliminated from their bodies – around 30 days later - the animals' performances returned to normal, suggesting the effect of B2M is reversible.
Some mice had been genetically engineered so that they couldn't make B2M. These animals performed equally well regardless of age. "It may not be this factor alone that causes the memory loss," says Benjamin Alman of the Hospital for Sick Children in Toronto, Canada, who is trying to find molecules in young blood that heal bones faster. "But it does raise the possibility that failing memory can be rescued by drugs that interfere with these circulating factors," he says. "The concept is very exciting, and would have been unthinkable a few years ago."
Two leading neurology researchers have proposed a theory that could unify scientists’ thinking about several neurodegenerative diseases and suggest therapeutic strategies to combat them. The theory and backing for it are described in the September 5, 2013 issue of Nature. Mathias Jucker and Lary Walker outline the emerging concept that many of the brain diseases associated with aging, such as Alzheimer’s and Parkinson’s, are caused by specific proteins that misfold and aggregate into harmful seeds. These seeds behave very much like the pathogenic agents known as prions, which cause mad cow disease, chronic wasting disease in deer, scrapie in sheep, and Creutzfeldt-Jakob disease in humans. Walker is research professor at Yerkes National Primate Research Center, Emory University. Jucker is head of the Department of Cellular Neurology at the Hertie Institute for Clinical Brain Research at the University of Tübingen and the German Center for Neurodegenerative Diseases. Unlike prion diseases, which can be infectious, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases can not be passed from person to person under normal circumstances. Once all of these diseases take hold in the brain, however, it is increasingly apparent that the clumps of misfolded proteins spread throughout the nervous system and disrupt its function. The authors were the first to show that a protein that is involved in Alzheimer’s disease – known as amyloid-beta – forms prion-like seeds that stimulate the aggregation of other amyloid-beta molecules in senile plaques and in brain blood vessels. Since then, a growing number of laboratories worldwide have discovered that proteins linked to other neurodegenerative disorders also share key features with prions. Age-related neurodegenerative disorders remain stubbornly resistant to the discovery of effective treatments. Jucker and Walker propose that the concept of pathogenic protein seeding not only could focus research strategies for these seemingly unrelated diseases, but it also suggests that therapeutic approaches designed to thwart prion-like seeds early in the disease process could eventually delay or even prevent the diseases.
A decade ago, Francis Collin's research lab at NIH helped discover the cause of the Hutchinson-Gilford progeria syndrome: a mutation in the lamin-A gene. Just a single letter substitution in the genetic code (C to T) creates a toxic version of the protein. The abnormal protein is missing a segment, and is no longer digestible by an enzyme called ZMPSTE24—essentially a molecular scissors. Without that final snip, the lamin-A protein causes molecular havoc.More recently, children who are completely missing the ZMPSTE24 enzyme have been identified, and they have an even more severe form of progeria called “restrictive dermopathy”. Many questions remain but now we are able to get a close up of ZMPSTE24 and understand how, and where, it normally modifies lamin-A.
Using x-ray crystallography, a team based at the UK’s University of Oxford figured out the enzyme’s molecular structure [2, 3]. A cross section of the 3D structure (seen above) reveals a cavernous inner chamber where the authors believe the final snip of lamin-A takes place. It also shows us how mutations in ZMPSTE24, which inhibit lamin-A processing, can also lead to these rare aging disorders. Knowing ZMPSTE24’s structure will help us better understand its clipping functions. It could also shed light on how this enzyme works in the normal aging processes—as well as in the accelerated aging of progeria. Ultimately, we hope it will also inform drug development for this devastating disease. Video Link: http://www.youtube.com/watch?v=7RHhRqDlImg References: [1] Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Nature. 2003 May 15;423(6937):293-8. Epub 2003 Apr 25. [2] The structural basis of ZMPSTE24-dependent laminopathies. Quigley A, Dong YY, Pike AC, Dong L, Shrestha L, Berridge G, Stansfeld PJ, Sansom MS, Edwards AM, Bountra C, von Delft F, Bullock AN, Burgess-Brown NA, Carpenter EP. Science. 2013 Mar 29;339(6127):1604-7. [3] Biochemistry. A protease for the ages. Michaelis S, Hrycyna CA. Science. 2013 Mar 9;339(6127):1529-30.
Brooke Greenberg (born January 8, 1993), is a now 20 year old girl from Reisterstown, Maryland, who has remained physically and cognitively similar to a toddler. She is about 30 inches (76 cm) tall, weighs about 16 pounds (7.3 kg), and has an estimated mental age of 9 months to 1 year. Brooke’s doctors have termed her condition Syndrome X. Brooke was born on January 8, 1993 at Sinai Hospital in Baltimore, Maryland, one month prior to her due date, weighing just four pounds (1.8 kg). She was born with anterior hip dislocation, a condition which caused her legs to be swiveled upwards, awkwardly, toward her shoulders; this was corrected surgically. Otherwise, Brooke appeared to be a normal infant.
In her first six years, Brooke Greenberg went through a series of unexplained medical emergencies from which she recovered. She had seven perforated stomach ulcers. She also suffered a seizure. This was followed by what was later diagnosed as a stroke; weeks later, no damage was detected. At age five, Brooke had a mass in her brain that caused her to sleep for 14 days. The doctors diagnosed the mass as a brain tumor. However, Brooke later awoke, and physicians found no tumor present. Brooke’s pediatrician, Dr. Lawrence Pakula, states that the source of her sudden illness remains a mystery.
Over the past several years, the Greenbergs visited many specialists, looking for an explanation for their daughter’s strange condition, and found she has a mutation in Chromosome 1. In 2001, when Dateline documented Brooke, she was still the size of a six-month-old infant, weighing just 13 lb (5.9 kg) at 27 inches (69 cm) tall. The family still had no explanation. Brooke Greenberg’s mother Melanie said: “They [the specialists] just said she’ll catch up. Then we went to the nutritionist, the endocrinologist. We tried the growth hormone…”. The growth hormone treatment had no effect. Howard, Brooke’s father, said: “I mean she did not put on an ounce or she did not grow an inch … That’s when I knew there was a problem.” After the growth hormone administration failed, the doctors, unable to diagnose a known condition, named her condition Syndrome X.
The Greenbergs made many visits to nearby Johns Hopkins Children’s Center, and even took Brooke to New York’s Mount Sinai Hospital, searching for information about their daughter’s condition. When geneticists sequenced Greenberg’s DNA, they found that the genes associated with the premature aging diseases were normal, unlike the mutated versions in patients with Werner syndrome and progeria.
In 2006, Dr. Richard Walker of the University of South Florida College of Medicine, said that Brooke’s body is not developing as a coordinated unit, but as independent parts that are out of sync. She has never been diagnosed with any known genetic disorder or chromosomal abnormality that would help explain why.
In 2009, Walker said: “There’ve been very minimal changes in Brooke’s brain … Various parts of her body, rather than all being at the same stage, seem to be disconnected.” Walker noted that Greenberg’s brain, for example, is not much more mature than that of a newborn infant. He estimates her mental age at around 9 months to a year old. Brooke can make gestures and recognize sounds, but cannot speak. Her bones are like those of a ten-year-old, and she still has her baby teeth, which have an estimated developmental age of about 8 years. Said Walker, “We think that Brooke’s condition presents us with a unique opportunity to understand the process of aging.”
Her telomeres seem to be shortening at the normal rate.
Yesterday, Brooke Greenberg and her family appeared on the Katie Couric Show as part of a show focused on medical mysteries. Greenberg, who is 20 years old, appears to be the age of a toddler. While the family does not know the root of Greenberg's apparent inability to age, Mount Sinai's Eric Schadt, who also appeared on the show with host Katie Couric, has been studying her genome. As Schadt notes in the clip below, in addition to figuring out the source of her disorder, Greenberg's genome could also help researchers learn more about the aging process.
Video Link: http://bcove.me/uesqzs6d
Life after death, for most people, is a faithful belief in a spiritual hereafter, a transfer to a higher, non-bodily consciousness. For cryonics enthusiasts, however, a “second life” – or more accurately, a resuscitated life with a little help from freezer storage – here on Earth is the goal. The Prospect of Immortality is a six-year study by UK photographer Murray Ballard, who has traveled the world pulling back the curtain on the amateurs, optimists, businesses and apparatuses of cryonics. “It’s not a large industry,” says Ballard, who visited the Alcor Life Extension Foundation in Phoenix, Arizona; the Cryonics Institute in Detroit, Michigan; KrioRus in Moscow, Russia; and Suspended Animation Inc in Boytan Beach, Florida; among others. Cryonics is the preservation of deceased humans in liquid nitrogen at temperatures just shy of its boiling point of −196°C/77 Kelvin. Cryopreservation of humans is not reversible with current science, but cryonicists hypothesize that people who are considered dead by current medical definitions may someday be recovered by using advanced future technologies. Stats are hard to come by, but it is estimated there are about 2,000 people signed up for cryonics and approximately 250 people currently cryopreserved. Over 100 pets have also been placed in vats of liquid nitrogen with the hopes of a future recovery. Ballard’s project began in 2006 after he read a news article, “Freezer Failure Ends Couple’s Hopes of Life After Death,” about a French couple who had been kept in industrial freezers beneath their chateau in the Loire valley. He phoned up a small group of UK cryonicists and attended their meetings and training sessions. Later, funding from an arts organization paid for two trips to the U.S. A chance meeting with one of the founders of KrioRus, a Russian cryonics organization, at a UK conference set up a memorable week-long trip to Moscow, St. Petersburg, and Vorenzh. There he photographed the two resting places of the first Russian cryonics neuro-patient. “I photographed her grave in a cemetery just outside St. Petersburg and the cryostat containing her head at the facility in Moscow.” Heads take up less storage space than whole bodies. They’re cheaper to store.
Researchers at King’s College London, Harvard University and Massachusetts General Hospital have identified for the first time a key factor responsible for declining muscle repair during ageing, and discovered how to halt the process in mice with a common drug.
Although an early study, the finding provides clues as to how muscles lose mass with age, which can result in weakness that affects mobility and may cause falls.
Published today in the journal Nature, and funded by the Biotechnology, and Biological Sciences Research Council, Harvard Stem Cell Institute and National Institutes of Health (US), the study looked at stem cells found inside muscle - which are responsible for repairing injury - to find out why the ability of muscles to regenerate declines with age. A dormant reservoir of stem cells is present inside every muscle, ready to be activated by exercise and injury to repair any damage. When needed, these cells divide into hundreds of new muscle fibres that repair the muscle. At the end of the repairing process some of these cells also replenish the pool of dormant stem cells so that the muscle retains the ability to repair itself again and again.
The researchers carried out a study on old mice and found the number of dormant stem cells present in the pool reduces with age, which could explain the decline in the muscle’s ability to repair and regenerate as it gets older. When these old muscles were screened the team found high levels of FGF2, a protein that has the ability to stimulate cells to divide. While encouraging stem cells to divide and repair muscle is a normal and crucial process, they found that FGF2 could also awaken the dormant pool of stem cells even when they were not needed. The continued activation of dormant stem cells meant the pool was depleted over time, so when the muscle really needed stem cells to repair itself the muscle was unable to respond properly.
Following this finding, the researchers attempted to inhibit FGF2 in old muscles to prevent the stem cell pool from being kick-started into action unnecessarily. By administering a common FGF2 inhibitor drug they were able to inhibit the decline in the number of muscle stem cells in the mice.
However, preventing or reversing muscle waste during old age in humans is still a way off, but this study has for the first time revealed a process which could be responsible for age-related muscle wasting, which is an extremely important finding.
The study was led by Justin Denney, PhD, assistant professor of sociology at Rice University. Researchers collected data from the Human Mortality Database for 1930-2000 to predict future life expectancy in 2055. Based on this research, not only has life expectancy stagnated in America, it trails several developed countries. For an American born today, life expectancy is around 78.49 years of age. Compared to countries with the highest life expectancies, Americans may be missing out on five to 10 years of life. Monaco has the highest life expectancy at 89.68 years while Macau at 84.43 and Japan at 83.91 are close behind. Imagine getting an extra decade to experience life and that's what many Americans are missing out on.
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Research from the Babraham Institute has developed a method to ‘time jump’ human skin cells by 30 years, turning back the aging clock for cells without losing their specialized function. Work by researchers in the Institute’s Epigenetics research program has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. The research is published in the journal eLife and whilst at an early stage of exploration, it could revolutionize regenerative medicine. How does it work? As we age, our cells’ ability to function declines and the genome accumulates marks of aging. Regenerative biology aims to repair or replace cells including old ones. One of the most important tools in regenerative biology is our ability to create ‘induced’ stem cells. The process is a result of several steps, each erasing some of the marks that make cells specialized. In theory, these stem cells have the potential to become any cell type, but scientists aren’t yet able to reliably recreate the conditions to re-differentiate stem cells into all cell types. The new method, based on the Nobel Prize winning technique scientists use to generate stem cells, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the whole process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialized cell function. In 2007, Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into stem cells which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called 'maturation phase transient reprogramming’, exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of skin cells (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells.
Contrary to what science once suggested, older people with a declining sense of smell do not have comprehensively dampened olfactory ability for odors in general -- it simply depends upon the type of odor. Researchers at the University of Copenhagen reached this conclusion after examining a large group of older Danes' and their intensity perception of common food odors. That older people aren't as good at smelling as they once were, is something that many can relate to. And, it has also been scientifically demonstrated. One's sense of smell gradually begins to decline from about the age of 55. Until now, it was believed that one's sense of smell broadly declined with increasing age. However, a study from the University of Copenhagen reports that certain food odors are significantly more affected than others. The Department of Food Science's Eva Honnens de Lichtenberg Broge and her fellow researchers have tested the ability of older Danes to perceive everyday food odors. The researchers measured how intensely older adults perceived different food odors, as well as how much they liked the odors. "Our study shows that the declining sense of smell among older adults is more complex than once believed. While their ability to smell fried meat, onions and mushrooms is markedly weaker, they smell orange, raspberry and vanilla just as well as younger adults. Thus, a declining sense of smell in older adults seems rather odor specific. What is really interesting is that how much you like an odor is not necessarily dependent on the intensity perception" says Eva Honnens de Lichtenberg Broge. For example, liking of seemed to be largely unaffected for fried meat, onions and mushrooms, despite the largest decline in intensity perception was seen for these specific odors. Also the ability to smell coffee declined, among other things, though they didn't like the aroma of coffee to the same degree as younger adults. The test subjects included 251 Danes between the ages of 60 and 98 and a control group consisting of 92 people between the ages of 20 and 39.
Scientists have estimated that the age of an individual does not indicate how likely they are to be infected by SARS-CoV-2. However, development of symptoms, progression of the disease, and mortality are age-dependent. There have been a large number of deaths due to the ongoing COVID-19 pandemic, and it has been shown that elderly individuals disproportionately develop severe symptoms and show higher mortality. A team of scientists, including Associate Professor Ryosuke Omori from the Research Center for Zoonoses Control at Hokkaido University, have modeled available data from Japan, Spain and Italy to show that susceptibility to COVID-19 is independent of age, while occurrence of symptomatic COVID-19, severity and mortality is likely dependent on age. Their results were published in the journal Scientific Reports on October 6, 2020. Causes of mortality in elderly individuals may be due to two factors: how likely they are to be infected due to their advanced age (age-dependent susceptibility), which is reflected in the number of cases; and, how likely they will be affected by a severe form of the disease due to their advanced age (age-dependent severity), which is reflected in the mortality rate. These factors are not fully understood for COVID-19. The scientists chose to analyse data from Italy, Spain and Japan to determine if any relationship between age, susceptibility and severity. These three countries were chosen as they have well recorded, publicly available data. As of May 2020, the mortality rate (number of deaths per 100,000) was 382.3 for Italy, 507.2 for Spain and 13.2 for Japan. However, despite the wide disparity in mortality rates, the age distribution of mortality (the proportional number of deaths per age group) was similar for these countries.
If only we could keep our bodies young, healthy and energetic, even as we attain the wisdom of our years. New research at the Weizmann Institute of Science suggests this dream could be at least partly obtainable in the future. The results of this research, led by Prof. Valery Krizhanovsky and Dr. Yossi Ovadya in the Molecular Cell Biology Department, were recently published in Nature Communications. The research began with an investigation into the way that the immune system is involved in a crucial activity: clearing away old, senescent cells that spell trouble for the body when they hang around. Senescent cells – not completely dead but suffering loss of function or irreparable damage – have been implicated in diseases of aging by promoting inflammation. The researchers used mice in which a crucial gene for this immune activity was missing. At two years (elderly, for mice), the bodies of these mice had a greater accumulation of senescent cells compared with the mice in which the gene for removing these cells was intact. The mice missing the gene suffered from chronic inflammation, and various functions in their bodies appeared to be diminished. They also looked older – and died earlier – than their normal counterparts. Next, the researchers gave the mice a drug that inhibits the function of certain proteins that help the aging cells survive in their senescent state, to see if this would contribute to the removal of these cells from the body. The drugs were administered to mice whose aging was a result of the malfunctions the group had uncovered in the immune system as well as those suffering premature aging from a different genetic error. The treated mice responded exceptionally well to the drug: Their blood tests and activity tests showed improvement, and their tissues appeared to be much closer to those of young mice. The scientists counted senescent cells, finding many fewer of them remaining in the treated mice’s bodies; and when they looked for signs of inflammation, they found that this, too, was significantly lower. The mice treated with the drug were more active and their median lifespan rose. The scientists intend to continue exploring ways to prompt the human body to remove its old senescent cells, particularly to find means of activating the immune system to do this job. That is, if future experimentation proves their theories correct, they could end up creating truly “anti-aging” therapies.
A protein that appears to be key in the development of Alzheimer's disease has been identified by scientists who say the discovery could provide a new drug target for dementia. Known as GPR3, the protein is believed to play an important role in reducing the buildup of amyloid plaques in the brain, a hallmark of Alzheimer's disease, said the findings in Wednesday's edition of Science Translational Medicine.
Research on mice with four different varieties of dementia showed that genetically deleting GPR3 resulted in cognitive improvement and reduced signs of disease in the brain. But since mouse models of Alzheimer's disease are not directly equivalent to the human condition, more research is needed to determine if the same process could work in people.
Researchers are encouraged by the fact that about half of all drugs currently on the market target this type of receptor, known as a G protein-coupled receptor. Also, autopsies on the brains of people with Alzheimer's have shown that a subset of patients show high levels of GPR3, and that these levels were associated with advancement of the disease.
The new study "is an example of how testing a drug target in multiple disease-relevant models can build a strong case to convince the pharmaceutical industry to launch a drug development program for Alzheimer's disease," the authors wrote. There is no cure for Alzheimer's disease, the most common type of dementia, and no drug treatment that has been shown to stop its progressions. More than 46 million people worldwide suffer from dementia, and cases are expected to balloon to 131.5 million by 2050 due to the aging population.
Last month a team of doctors and scientists made the case to regulators at the Food and Drug Administration (FDA) to consider approving anti-aging drugs as a new pharmaceutical class. Such a designation would treat aging as disease rather than a natural process, potentially opening the door to government funding for anti-aging drug trials.
To some, such a drug may seem impossible. Yet, the physiologic basis for it exists. In fact, some candidate drugs, such as metformin, used to treat diabetes, are already being safely used for treating other conditions. Many scientists believe that designing an anti-aging medication is a matter of “when,” not “if.”
Yet the very idea of a quick-fix pill for stopping, and perhaps even reversing, nature’s intricate biologic clock thus far has proven to be a hubristic notion. There is much we need to learn about how the aging process works. And while some drugs have shown promise as anti-aging treatments in the lab, we don’t know how well, or even if, they will work in humans.
Aging remains a mystery. While the visible changes of gray hair and wrinkles are unmistakable, what goes on inside your body is less clear. According to leading theories, aging is an accumulation of damage inside your cells, the building blocks of your tissues.
Cells continually receive cues from your body and the environment that can accelerate age-driving processes such as oxidative damage and inflammation. These processes are interdependent – woven in a complex maze that is perplexing and daunting for researchers.
Rather than trying to extend life by individually targeting prevention and treatment of common age-related diseases such as heart disease, stroke and cancer, scientists are looking for a “master control switch” that can regulate the divergent and overlapping pathways that contribute to aging itself.
Since aging is the biggest risk factor for developing such diseases, an anti-aging medication that can flip this switch would theoretically not only slow or stop aging but would also defer many diseases associated with aging. And that is what some of the drugs scientists are investigating may be able to do.
MIT neuroscientists have found new evidence that suggests that a failure to repair damaged DNA could underlie not only ALS, but also other neurodegenerative disorders such as Alzheimer’s disease. These findings imply that drugs that bolster neurons’ DNA-repair capacity could help ALS patients, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and senior author of a paper describing the ALS findings in the Sept. 15, 2013 issue of Nature Neuroscience.
Neurons are some of the longest-living cells in the human body. While other cells are frequently replaced, our neurons are generally retained throughout our lifetimes. Consequently, neurons can accrue a lot of DNA damage and are especially vulnerable to its effects.
“Our genome is constantly under attack and DNA strand breaks are produced all the time. Fortunately, they are not a worry because we have the machinery to repair it right away. But if this repair machinery were to somehow become compromised, then it could be very devastating for neurons,” Tsai says.
Tsai’s group has been interested in understanding the importance of DNA repair in neurodegenerative processes for several years. In a study published in 2008, they reported that DNA double-strand breaks precede neuronal loss in a mouse model that undergoes Alzheimer’s disease-like neurodegeneration and identified a protein, HDAC1, which prevents neuronal loss under these conditions.
HDAC1 is a histone deacetylase, an enzyme that regulates genes by modifying chromatin, which consists of DNA wrapped around a core of proteins called histones. HDAC1 activity normally causes DNA to wrap more tightly around histones, preventing gene expression. However, it turns out that cells, including neurons, also exploit HDAC1’s ability to tighten up chromatin to stabilize broken DNA ends and promote their repair.
In a paper published earlier this year in Nature Neuroscience, Tsai’s team reported that HDAC1 works cooperatively with another deacetylase called SIRT1 to repair DNA and prevent the accumulation of damage that could promote neurodegeneration.
When a neuron suffers double-strand breaks, SIRT1 migrates within seconds to the damaged sites, where it soon recruits HDAC1 and other repair factors. SIRT1 also stimulates the enzymatic activity of HDAC1, which allows the broken DNA ends to be resealed.
SIRT1 itself has recently gained notoriety as the protein that promotes longevity and protects against diseases including diabetes and Alzheimer’s disease, and Tsai’s group believes that its role in DNA repair contributes significantly to the protective effects of SIRT1.
In an attempt to further unveil other partners that work with HDAC1 to repair DNA, Tsai and colleagues stumbled upon a protein called Fused In Sarcoma (FUS). This finding was intriguing, Tsai says, because the FUS gene is one of the most common sites of mutations that cause inherited forms of ALS.
The MIT team found that FUS appears at the scene of DNA damage very rapidly, suggesting that FUS is orchestrating the repair response. One of its roles is to recruit HDAC1 to the DNA damage site. Without it, HDAC1 does not appear and the necessary repair does not occur. Tsai believes that FUS may also be involved in sensing when DNA damage has occurred.
At least 50 mutations in the FUS gene have been found to cause ALS. The majority of these mutations occur in two sections of the FUS protein. The MIT team mapped the interactions between FUS and HDAC1 and found that these same two sections of the FUS protein bind to HDAC1.
They also generated four FUS mutants that are most commonly seen in ALS patients. When they replaced the normal FUS with these mutants, they found that the interaction with HDAC1 was impaired and DNA damage was significantly increased. This suggests that those mutations prevent FUS from recruiting HDAC1 when DNA damage occurs, allowing damage to accumulate and eventually leading to ALS.
Researchers from the Instituto de Medicina Oncológica y Molecular de Asturias have found that a protein responsible for accelerated aging disorders can dramatically slow down the spread of cancers. The team revealed that prelamin A, responsible for accelerated ageing in a condition called progeria, can prevent the progression of malignant or cancerous tumours. They achieved this by using mosaic mouse models, genetically modified mice bearing the protein prelamin A in half of their cells. Ageing and cancer are intimately related processes, but their links are complex. The risk of developing tumours increases with age, but some of the mechanisms favouring ageing can also slow down the appearance and development of cancer. The results from this study represent an advance in the understanding of the underlying biological mechanisms that link age and cancer development, as well as possible new drug targets in the future. "Mice with prelamin A in all their cells age more quickly and do not live longer than 4-5 months, which extremely hampers the study of cancer, as there is no time for the disease to fully develop,"indicates Jorge de la Rosa. Researchers previously developed mice that have an underactive ZMPSTE24 gene that mimic the ageing disorder progeria to test for possible treatments. This causes the protein prelamin A to accumulate and in turn results in progeria. To better study the association of ageing and cancer development, the team developed a mosaic model where ZMPSTE24 was underactive in half of the cells and working normally in the other half of the cells. "Mosaic mice, however, live as long as normal mice, up to two to three years, and they keep 50% of cells with prelamin A in all their tissues throughout lifespan, which has permitted us to study the effect of this protein on cancer," comments Juan Cadiñanos. The team found that the mosaic mice were completely healthy, without any of the physical deformities shown by mice with prelamin A-induced progeria: reduced size and weight, loss of fat, infertility and premature death. This suggests that it might not be necessary to correct the defects in all the cells of patients with progeria, but only some. These results provide hope for a successful treatment of patients with progeria in the future.
Researchers have identified for the first time a key factor responsible for declining muscle repair during aging, and discovered that a common drug halts the process in mice. A dormant reservoir of stem cells is present inside every muscle, ready to be activated by exercise and injury to repair any damage. When needed, these cells divide into hundreds of new muscle fibers that repair the muscle. At the end of the repairing process some of the cells also replenish the pool of dormant stem cells so that the muscle retains the ability to repair itself again and again. The researchers carried out a study on old mice and found the number of dormant stem cells present in the pool reduces with age, which could explain the decline in the muscle’s ability to repair and regenerate as it gets older. When these old muscles were screened the team found high levels of FGF2, a protein that has the ability to stimulate cells to divide. While encouraging stem cells to divide and repair muscle is a normal and crucial process, they found that FGF2 could also awaken the dormant pool of stem cells even when they were not needed. The continued activation of dormant stem cells meant the pool was depleted over time, so when the muscle really needed stem cells to repair itself the muscle was unable to respond properly. Researchers then attempted to inhibit FGF2 in old muscles to prevent the stem cell pool from being kick-started into action unnecessarily. By administering a common FGF2 inhibitor drug they were able to inhibit the decline in the number of muscle stem cells in the mice. “Preventing or reversing muscle wasting in old age in humans is still a way off, but this study has for the first time revealed a process which could be responsible for age-related muscle wasting, which is extremely exciting,” says Albert Basson, Senior Lecturer from the department of craniofacial development and stem cell biology at the King’s College London Dental Institute. “The finding opens up the possibility that one day we could develop treatments to make old muscles young again. If we could do this, we may be able to enable people to live more mobile, independent lives as they age.”
Attention seniors: French scientists have developed a process that permanently dyes white hair without harmful chemicals. Philippe Walter and colleagues soaked white hairs in a solution containing fluorescent gold nanoparticles. The hairs turned pale yellow and then darkened to a deep brown. The color remained even after repeated washings.
Via Ray and Terry's
The human immune system weakens with the passing of time, thus making us more susceptible to cancer and infectious diseases. This aging also affects the ability of our organism to take advantage of vaccination. A new study conducted by scientists at the Stanford University School of Medicine shows that if a certain protein is blocked, the response of the cells to vaccines and other atingens like cancer or microbial antigens can be restored. The levels of this particular protein increase with age.
Doctor Jorg Goronzy, a professor of rheumatology and the lead author of the paper says that this discovery is very important for long-term therapies. He added that in the near future the possibility of countering the effects of aging on our immune system might be achievable through pharmacology.
The research team discovered a protein, named DUSP6 (Dual specificity phosphatase 6), that impedes the capacity of an entire class of immune cells, thus preventing them from interacting with foreign bodies or substances. These substances include pathogens and vaccines. Another finding was that of a possible compound that is able to restore the responsiveness of the immune cells back to normal, once the DUSP6 protein is inhibited.
Dr Goronzy says that the human immune system decades with aging, starting from around the age of 40. Goronzy added that even though almost 90% of adults below the age of 40 respond to vaccines, the rate of responsiveness drops to almost 40% after the age of 60. An example of poor responsiveness in older patients is that of influenza deaths, most of which are registered in patients older than 65.
In a long-running study, rhesus monkeys whose caloric intake was restricted by 30 percent didn’t live any longer than their normal-weight peers. For 25 years, the rhesus monkeys were kept semi-starved, lean and hungry. The males’ weights were so low they were the equivalent of a 6-foot-tall man who tipped the scales at just 120 to 133 pounds. The hope was that if the monkeys lived longer, healthier lives by eating a lot less, then maybe people, their evolutionary cousins, would too. Some scientists, anticipating such benefits, began severely restricting their own diets. The results of this major, long-awaited study, which began in 1987, are finally in. But it did not bring the vindication calorie restriction enthusiasts had anticipated. It turns out the skinny monkeys did not live any longer than those kept at more normal weights. Some lab test results improved, but only in monkeys that were put on the diet when they were old. The causes of death — cancer, heart disease — were the same in both the underfed and the normally fed monkeys. Lab test results showed lower levels of cholesterol and blood sugar in the male monkeys that started eating 30 percent fewer calories in old age, but not in the females. Males and females that were put on the diet when they were old had lower levels of triglycerides, which are linked to heart disease risk. Monkeys put on the diet when they were young or middle-aged did not get the same benefits, though they had less cancer. But the bottom line was that the monkeys that ate less did not live any longer than those that ate normally. Rafael de Cabo, lead author of the diet study, published online on Wednesday in the journal Nature, said he was surprised and disappointed that the underfed monkeys did not live longer. Like many other researchers on aging, he had expected an outcome similar to that of a 2009 study from the University of Wisconsin that concluded that caloric restriction did extend monkeys’ life spans.
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