A new study published in Journal of the American Geriatrics Society indicates that cancer survivors, especially older ones, are more likely to experience faster functional decline as they age, compared with those without a history of cancer.
For the study, 1728 men and women (aged 22 to 100 years) were evaluated from 2006 to 2019, with 359 of these adults reporting a history of cancer. Among all participants, a history of cancer was associated with a 1.42 greater odds of weak grip strength. Those with a history of cancer and over 65 had a 1.61 greater odds of slow gait speed than those with no cancer history, and also had lower physical performance scores. Additionally, compared with those with no history of cancer, older individuals with a history of cancer experienced steeper declines in grip strength and gait speed. Reduced prefrontal cortex area is one of the factors thought to contribute to slow gait.
“Findings from our study add to the evidence that cancer and its treatment may have adverse effects on aging-related processes, putting cancer survivors at risk for accelerated functional decline,” said senior author Lisa Gallicchio, PhD, of the National Cancer Institute. “Understanding which cancer survivors are at highest risk, and when the accelerated decline in physical functioning is most likely to begin, is important in developing interventions to prevent, mitigate, or reverse the adverse aging-related effects of cancer and its treatment.”
A new study has discovered that people who live to be 100 or older have a unique microbiome that may protect against certain bacterial infections including those caused by multidrug-resistant bacteria. The findings, published in Nature, could point to new ways to treat chronic inflammation and bacterial disease.
A team of researchers studied microbes from faecal samples of 160 Japanese centenarians who had an average age of 107. They found that centenarians, compared to people aged 85 to 89 and those between 21 and 55, had higher levels of several bacterial species that produce molecules called secondary bile acids. Secondary bile acids are generated by microbes in the colon and are thought to help protect the intestines from pathogens and regulate the body’s immune responses.
Next, the researchers treated common infection-causing bacteria in the lab with the secondary bile acids that were elevated in the centenarians. One molecule, called isoalloLCA, was found to strongly inhibit the growth of the antibiotic-resistant bacterium Clostridioides difficile. Feeding mice infected with C. difficile diets supplemented with isoalloLCA similarly suppressed levels of the bacteria. The team also found that isoalloLCA potently inhibited or killed many other gram positive pathogens, suggesting that isoalloLCA may play a role in keeping the delicate equilibrium of microbial communities in a healthy gut.
“The ecological interaction between the host and different processes in bacteria really suggests the potential of these gut bugs for health maintenance,” said Plichta, a computational scientist at the Broad.
Additional studies from different regions around the world with more participants and longer duration could help find a causal link between longevity and bile acids. The bacteria identified in this study could help researchers in the meantime discover how to treat infections caused by antibiotic-resistant bacteria by manipulating bile acid.
“A unique cohort, international collaboration, computational analysis, and experimental microbiology all enabled this discovery that the gut microbiome holds the keys to healthy aging,” said co-first author Xavier, core institute member at the Broad. “Our collaborative work shows that future studies focusing on microbial enzymes and metabolites can potentially help us identify starting points for therapeutics.”
The University of Surrey has developed an artificial intelligence (AI) model that identifies chemical compounds that promote healthy ageing, which could help the development of pharmaceuticals for human lifespan extension.
In a paper published in Scientific Reports, a team of chemists from Surrey built a machine learning model based on the information from the DrugAge database to predict whether a compound can extend the life of Caenorhabditis elegans, a translucent worm whose metabolism is similar to humans. Because the worm has such a short lifespan, the researchers were able to test the effectiveness of the compounds.
The AI model identified three compounds that have an 80 percent chance of increasing the lifespan of elegans:
flavonoids (anti-oxidant pigments found in plants that promote cardiovascular health, examples include certain spices and herbs),
fatty acids (such as omega 3), and
organooxygens (compounds that contain carbon to oxygen bonds, such as alcohol).
Co-author Sofia Kapsiani, final year undergraduate student at the University of Surrey, said: “Ageing is increasingly being recognized as a set of diseases in modern medicine, and we can apply the tools of the digital world, such as AI, to help slow down or protect against ageing and age-related diseases. Our study demonstrates the revolutionary ability of AI to aid the identification of compounds with anti-aging properties.”
Commenting on the research, lead author Dr Brendan Howlin, Senior Lecturer in Computational Chemistry at the University of Surrey, said: “This research shows the power and potential of AI, which is a specialty of the University of Surrey, to drive significant benefits in human health.”
Journal information: “Random forest classification for predicting lifespan-extending chemical compounds” by Sofia Kapsiani and Brendan J. Howlin, 5 July 2021, Scientific Reports. DOI: 10.1038/s41598-021-93070-6
Findings from a new study into ‘junk DNA’ have brought scientists one step closer to solving the mysteries of ageing and cancer.
Jiyue Zhu, a professor in the College of Pharmacy and Pharmaceutical Sciences, led a team which recently identified a DNA region known as VNTR2-1 which seems to drive activity of the telomerase gene, which has been shown to prevent ageing in certain types of cells. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).
The telomerase gene controls the activity of the telomerase enzyme, which helps produce telomeres, the caps at the end of each strand of DNA that protect the chromosomes within our cells and which shorten over time until cells are no longer able to divide.
However, in certain cell types, such as reproductive cells and cancer cells, the telomerase gene’s activity ensures that telomeres are reset to the same length when DNA is copied. This is essentially what restarts the aging clock in new offspring but is also the reason why cancer cells can continue to multiply and form tumors.
Understanding how the telomerase gene is regulated and activated and why it is only active in certain types of cells could someday be the key to understanding how humans age, as well as how to stop the spread of cancer. That is why Prof Zhu has focused the past 20 years of his career as a scientist solely on the study of this gene.
Zhu said that VNTR2-1’s discovery is especially noteworthy due to the type of DNA sequence it represents.
“Almost 50% of our genome consists of repetitive DNA that does not code for protein,” noted Prof Zhu. “These DNA sequences tend to be considered as ‘junk DNA’ or dark matter in our genome, and they are difficult to study. Our study describes that one of those units actually has a function in that it enhances the activity of the telomerase gene.”
In previous work, deleting the DNA sequence from human and mouse cancer cells caused telomeres to shorten, cells to age, and tumours to stop growing. They conducted a subsequent study measuring the length of the sequence in DNA samples taken from Caucasian and African American centenarians and control participants in the Georgia Centenarian Study, a study that followed a group of people aged 100 or above between 1988 and 2008. The researchers found that the length of the sequence ranged from as short as 53 repeats of the DNA to as long as 160 repeats.
“It varies a lot, and our study actually shows that the telomerase gene is more active in people with a longer sequence,” Prof Zhu said.
Since very short sequences were found only in African American participants, they looked more closely at that group and found that there were relatively few centenarians with a short VNTR2-1 sequence as compared to control participants. However, Prof Zhu said that a shorter sequence does not necessarily translate to a shorter lifespan, since the telomerase gene is less active with possibly a shorter telomere length which could reduce cancer risk.
“Our findings are telling us that this VNTR2-1 sequence contributes to the genetic diversity of how we age and how we get cancer,” Prof Zhu said. “We know that oncogenes–or cancer genes–and tumor suppressor genes don’t account for all the reasons why we get cancer. Our research shows that the picture is a lot more complicated than a mutation of an oncogene and makes a strong case for expanding our research to look more closely at this so-called junk DNA.”
Prof Zhu observed that many African Americans in the United States for generations have Caucasian ancestry, which could have added this sequence. So he and his team hope to next be able to study the sequence in an African population.
Researchers have discovered a link between cognitive decline and accelerated bone loss, and found that cognitive decline over five years increased future fracture risk in women. There was a less strong association in men.
The 16-year study enrolling individuals aged 65 and over was led by the Garvan Institute of Medical Research and , and has uncovered a potential new approach to help identify older people who may be at risk of fracture. “Bone loss and cognitive decline are major public health issues, but both are ‘silent diseases’ that can go undetected and untreated for long periods, often until the conditions are severely progressed,” says Professor Jacqueline Center, Head of the Clinical Studies and Epidemiology lab at Garvan, endocrinologist at St Vincent’s Hospital and senior author of the findings published in the Journal of Bone and Mineral Research.
“Our study has revealed a link between the two in women, which suggests that cognition should be monitored together with bone health, as a decline in one could mean a decline in the other. These findings may help refine best practice guidelines of how cognition and bone health are monitored in older age, to ensure appropriate treatment can be more effectively administered.”
A growing problem with an ageing population
Osteoporosis affects some 200 million people worldwide, and more than 35 million for dementia — numbers set to double over the next 20 years due to rising life expectancy.
“Cognitive decline and bone loss both result in increased disability, loss of independence and an increased risk of mortality. There is some evidence that older individuals with dementia have a higher risk of hip fractures, but whether the decline of both bone and cognitive health are linked over time has not been studied,” said first author Dr Dana Bliuc from the Garvan Institute.
“We set out to understand the long-term association, with our study the first to investigate both cognitive and bone health data over more than 15 years.”
Data was drawn from the Canadian Multicentre Osteoporosis Study (CaMos), which has monitored skeletal health in community-dwelling people since 1995. The researchers examined cognitive and bone health measurements of 1741 women and 620 men aged 65 years and older, who were free of cognitive decline symptoms at the study outset.
Cognition link to bone health
“After adjusting for all other variables, we observed a significant link between a decline in cognitive health and bone loss in women. This association was weaker and not statistically significant in men,” said Dr Bliuc.
“Interestingly, we also saw that cognitive decline over the first five years was associated with a 1.7-fold increase in future fracture risk in women in the subsequent 10 years. This was independent of the level of bone loss,” Dr Bliuc added.
“While this study could not identify a causal link – whether a decline in cognitive function leads to a decline in bone loss, or vice versa – it suggests that cognitive decline should be monitored along with bone health, as a decline in one may signal the need for increased vigilance in the other,” said Professor Center.
The researchers add that the link could potentially be mediated by a third factor, such as oestrogen deficiency, linked to bone loss and cognitive decline. This research also opens the door for additional studies into what the link between these two common conditions may be.
“What our study highlights is that cognitive health is potentially an important factor for providing more information to individuals and their health professionals on fracture risk, and ultimately improve health outcomes for our older population,” said Professor Center.
Journal information: Bliuc, D., et al. (2021) Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study. Journal of Bone & Mineral Research. doi.org/10.1002/jbmr.4402.
Contrary to previously held scientific belief, the declining sense of smell in older people is not uniform, and their liking of many smells remains the same. Researchers at the University of Copenhagen reached this conclusion after examining a large group of older Danes’ and their intensity perception of common food odours.
The decline in smell has been demonstrated scientifically. Sense of smell gradually begins to decline from about the age of 55, and 75% of those over 80 show major olfactory impairment. While it was previously believed that one’s sense of smell broadly declined with increasing age, a study from the University of Copenhagen reports that certain food odours are significantly more affected than others.
Eva Honnens de Lichtenberg Broge and her fellow researchers tested the ability of older Danes to perceive everyday food odours. The researchers measured how intensely older adults perceived different food odours — as well as how much they liked the odours.
“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 odour is not necessarily dependent on theintensity perception,” observed Eva Honnens de Lichtenberg Broge.
For example, liking seemed to be largely unaffected for fried meat, onions and mushrooms, despite the largest decline in intensity perception was seen for these specific odors. 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 younger group consisting of 92 people between the ages of 20 and 39.
Everyday food odours
Instead of using odours of chemical origin, which is commonly the procedure when testing the sense of smell, Eva Honnens de Lichtenberg Broge developed a test kit including 14 natural food odours familiar from everyday life, including bacon, onions, toast, asparagus, coffee, cinnamon, orange and vanilla. The odours, mainly made from essential oils, were presented to participants by sniffing sticks.
The food odours were chosen based upon commonly consumed foods and dishes that older people often eat and enjoy most according to meal plans and surveys from a Danish catering company that provides food for the elderly.
What’s the story?
The researchers can only speculate as to why the declining sense of smell in older adults seems to be odours specific, especially for savoury food smells and why, in some cases, liking is largely unaffected.
“This may be due to the fact that these are common food odours in which saltiness or umami is a dominant taste element. It is widely recognised that salty is the basic taste most affected by aging. Since taste and smell are strongly associated when it comes to food, our perception of aroma may be disturbed if one’s taste perception of saltiness is impaired to begin with,” Eva Honnens de Lichtenberg Broge suggested.
Nutriton and quality of life
The researchers hope that their findings will help improve nutrition for the elderly. While the sense of smell is important for stimulating appetite and our serotonin levels as well, according to Eva Honnens de Lichtenberg Broge, their study demonstrates that the sensitivity of one’s sense of smell need not be decisive — participants’ liking of certain foods remained unchanged.
“Our results show that as long as a food odour is recognisable, its intensity will not determine whether or not you like it. So, if one wants to improve food experiences of older adults, it is more relevant to pay attention to what they enjoy eating than it is to wonder about which aromas seem weaker to them,” concluded Eva Honnens de Lichtenberg Broge.
Journal information: de Lichtenberg Broge, E.H., et al. (2021) Changes in perception and liking for everyday food odors among older adults. Food Quality and Preference. doi.org/10.1016/j.foodqual.2021.104254.
A team of researchers have found evidence of mouse and human germline cells that suggest they can reset their biological age.
As animals age, cell divisions run into replication errors and other external factors (such as exposure to pollutants) lead to gradual decay in cell quality; all of this is part of the natural ageing process. Eventually, cells become senescent and no longer able to divide in response to injury or wear and tear. In a new effort to understand this, researchers have found evidence that shows germline cells have a mechanism to effectively reset this process, enabling offspring to reset their ageing clocks.
Germline cells pass on genetic material from parent to offspring during the reproductive process. For many years, scientists have wondered why these cells do not inherit the age of their parents. And for many years, they assumed that the cells were ageless, but recent work has shown that they do, in fact, age. So that raised the question of how offspring are able to begin their lives with fresh cells.
To find out, the researchers at Brigham and Women’s Hospital and Harvard Medical School used molecular clocks to track the ageing process of mouse embryos. These clocks measure epigenetic changes in cells, and using them, the researchers continuously compare the biological age of embryos (apparent age based on reactions to epigenetic changes) with their chronological age. They found that the biological age of the mouse embryos remained constant through initial cell division after an egg was fertilised. However, about a week later, after embryo implantation in the uterus, the biological age of the embryos dropped. Some mechanism, it seems, had reset the biological age of the embryo back to zero.
Turning to human embryos, the team was unable to track ageing in human embryos because ethics rules forbid such research, but they still managed evidence suggesting that human embryos also reset their clocks. They plan to continue seeking the mechanism behind the reset process. The team’s findings were published in the journal Science Advances.
Researchers have discovered that failing to dispose of old photoreceptor cells leads to age-related macular degeneration.
The estimated number of people worldwide with age-related macular degeneration in 2020 was 196 million, increasing to 288 million in 2040. Though more than 50 genes are associated with the condition, the precise mechanism is unknown. Most people have a form of the condition, for which there are no known effective treatments.
In order to develop new therapies to treat the disease, University of Maryland School of Medicine (UMSOM) researchers are starting to understand what goes wrong in the disease. Using human and mice tissue, researchers showed that the process which removes the eye’s old, damaged light sensors is disrupted in macular degeneration.
Previously, the lead researcher had found out that many families with hearing disorders had genetic mutations in the gene for the CIB2 protein, and later work also showed that CIB2 was needed for vision in a large human family, as well as in zebrafish. Now, in this latest study, his team built on that previous work to dissect the intricate cell mechanisms behind retinal degeneration.
The team compared healthy mouse eyes to those from a mouse with the CIB2 protein genetically deleted. These CIB2 mutant mice were not disposing of their old light sensor proteins, called photoreceptors, like healthy mouse eyes did.
“Photoreceptors continue growing in tiny columns in the eye, but over time, light damages the photoreceptors. To combat this, support cells in the eye slowly munch on the old, damaged photoreceptors, keeping the columns the correct length,” explained first author Saumil Sethna, PhD, at the University of Maryland School of Medicine. “If the photoreceptors are not removed, or if the process is backed up due to slow digestion by the support cells, like in the CIB2 mutant mice, the undigested material builds up over time, which may contribute to blindness.”
The researchers then identified several components in this photoreceptor recycling process, including a group of proteins collectively called mTORC1, which is involved in many human diseases, including cancer, obesity, and epilepsy.
Since mTORC1 (part of a family called mTOR) is a decision-maker for many cellular functions including cleaning up cellular debris, the researchers examined mTORC1’s activity in the CIB2 mutant mice and saw that it was overactive. mTORC1 was also found to be overactive in eye tissue of people with a form of age-related macular degeneration. The findings therefore indicate that drugs against mTORC1 may be effective treatments for the most common type of age-related macular degeneration, according to the researcher. “Researchers have tested many small molecules directed at mTORC1 to treat various diseases, but the problem is that mTOR is needed for so many other cell functions that there are major side-effects when you tinker with it,” said senior author Zubair M Ahmed, PhD, Professor of Otorhinolaryngology-Head & Neck Surgery and Ophthalmology at the University of Maryland School of Medicine. “In our study, we found a backdoor way to regulate mTORC1, which may bypass many of the unpleasant side-effects that normally occur with suppressing mTORC1. We think we may be able to use our new knowledge of this mechanism to develop treatments for age-related macular degeneration and other diseases as well.”
A new study for the first time provides quantitative evidence linking psychological stress to greying hair in people.
Greying of hair, a phenomenon still poorly understood in humans, first starts in white individuals at 34, while black individuals only start greying around 44. While it may seem intuitive that stress can accelerate greying, the researchers were surprised to discover that hair colour can actually be restored when stress is eliminated, a finding that contrasts with a recent study in mice that suggested that stressed-induced grey hairs are permanent.
The study holds clues to understanding ageing beyond just confirming the old tale about stress and ageing, said the study’s senior author Martin Picard, PhD, associate professor of behavioral medicine (in psychiatry and neurology) at Columbia University Vagelos College of Physicians and Surgeons.
“Understanding the mechanisms that allow ‘old’ grey hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human ageing in general and how it is influenced by stress,” Prof Picard said.
“Our data add to a growing body of evidence demonstrating that human ageing is not a linear, fixed biological process but may, at least in part, be halted or even temporarily reversed.”
Hair can help understand ageing
“Just as the rings in a tree trunk hold information about past decades in the life of a tree, our hair contains information about our biological history,” Picard said. “When hairs are still under the skin as follicles, they are subject to the influence of stress hormones and other things happening in our mind and body. Once hairs grow out of the scalp, they harden and permanently crystallise these exposures into a stable form.”
Though it has long been believed by people that psychological stress can increase grey hairs, it has remained a matter of scientific debate due to a lack of sensitive methods that can precisely correlate times of stress with hair pigmentation at a single-follicle level.
Splitting hairs to document hair pigmentation
Ayelet Rosenberg, first author on the study and a student in Picard’s laboratory, developed a new method for making high resolution images of tiny slices of human hairs to measure the extent of pigment loss — greying — in each of those slices. Each slice, about 1/20th of a millimetre wide, represents about an hour of hair growth.
“If you use your eyes to look at a hair, it will seem like it’s the same color throughout unless there is a major transition,” Picard says. “Under a high-resolution scanner, you see small, subtle variations in color, and that’s what we’re measuring.”
For the study 14 volunteers were asked to review their calendars and rate each week’s level of stress in a stress diary. Analysing individual hair samples, the researchers compared the results with each volunteer’s stress diary.
Right away, it was noticed that some grey hairs naturally regain their original color, which had never been quantitatively documented, Picard said.
When hairs were aligned with stress diaries, it revealed striking associations between stress and hair greying and, in some cases, a reversal of greying with the lifting of stress.
“There was one individual who went on vacation, and five hairs on that person’s head reverted back to dark during the vacation, synchronized in time,” Picard said.
Blame the mind-mitochondria connection
Measuring levels of different proteins in the hairs and how protein levels changed over the length of each hair, the researchers came up with a model showing that mitochondria were responsible for greying.
“We often hear that the mitochondria are the powerhouses of the cell, but that’s not the only role they play,” Picard said. “Mitochondria are actually like little antennas inside the cell that respond to a number of different signals, including psychological stress.”
The mitochondria connection between stress and hair colour is a different mechanism than found in a recent study of mice, where stress-induced greying was caused by an irreversible loss of stem cells in the hair follicle.
“Our data show that greying is reversible in people, which implicates a different mechanism,” said co-author Ralf Paus, PhD, professor of dermatology at the University of Miami Miller School of Medicine. “Mice have very different hair follicle biology, and this may be an instance where findings in mice don’t translate well to people.”
Hair re-pigmentation possible only for some
Stress reduction is a good idea, but it won’t necessarily get rid of your grey hairs.
“Based on our mathematical modeling, we think hair needs to reach a threshold before it turns grey,” Picard said. “In middle age, when the hair is near that threshold because of biological age and other factors, stress will push it over the threshold and it transitions to grey.
“But we don’t think that reducing stress in a 70-year-old who’s been grey for years will darken their hair or increasing stress in a 10-year-old will be enough to tip their hair over the grey threshold.”
Researchers have discovered that the pituitary gland in mice ages due to an age-related form of chronic inflammation — which raises the possibility of slowing or even partially repairing this process.
The pituitary gland is a small, globular gland located underneath the brain that plays a major role in the hormonal system, explained Professor Hugo Vankelecom, a stem cell biologist from the Department of Development and Regeneration at KU Leuven. “My research group discovered that the pituitary gland ages as a result of a form of chronic inflammation that affects tissue and even the organism as a whole,” he said. “This natural process usually goes unnoticed and is referred to as ‘inflammaging’ — a contraction of inflammation and ageing. Inflammaging has previously been linked to the ageing of other organs.”
Because of the pituitary’s pivotal role in the body, its ageing may contribute to the reduction of hormonal processes and hormone levels in our body – such as in menopause.
The study also provides significant insight into the stem cells in the ageing pituitary gland. In 2012, Prof Vankelecom and colleagues showed that a prompt reaction of these stem cells to injury in the gland leads to repair of the tissue, even in adult animals.
“As a result of this new study, we now know that stem cells in the pituitary do not lose this regenerative capacity when the organism ages. In fact, the stem cells are only unable to do their job because, over time, the pituitary becomes an ‘inflammatory environment’ as a result of the chronic inflammation. But as soon as the stem cells are taken out of this environment, they show the same properties as stem cells from a young pituitary.”
Could damage be repaired?
This insight opens up a number of potential therapeutic avenues: would it be possible to reactivate the pituitary? This wouldn’t just involve slowing down hormonal ageing processes, but also repairing the damage caused by a tumour in the pituitary, for example.
“No fewer than one in every 1000 people is faced with this kind of tumour — which causes damage to the surrounding tissue — at some point.
“The quality of life of many of these patients would be drastically improved if we could repair this damage. We may be able to do so by activating the stem cells already present — for which our present study also provides new indications — or even by transplanting cells. That said, these new treatment options are not quite around the corner just yet, as the step from fundamental research to an actual therapy can take years to complete. For the time being, our study sets out a potential direction for further research.”
The study also brings up another interesting approach: using anti-inflammatory drugs to slow down pituitary ageing or even rejuvenate an ageing pituitary. “Several studies have shown that anti-inflammatory drugs may have a positive impact on some ageing organs. No research has yet been performed on this effect in relation to the pituitary.”
From mice to humans
Since Prof Vankelecom and colleagues studied the pituitary of mice, further research is required to demonstrate whether their findings also apply to humans. Prof Vankelecom cautioned, however: “Mice have a much greater regeneration capacity than humans.
“They can repair damaged teeth, for instance, while humans have lost this ability over the course of their evolution. Regardless, there are plenty of signs suggesting that pituitary processes in mice and humans are similar, and we have recent evidence to hand that gene expression in the pituitaries of humans and mice is very similar. As such, it is highly likely that the insights we gained will equally apply to humans.”
Source: KU Leuven
Journal information: Vennekens, A., et al. (2021) Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2100052118.
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