An exhaustive four year-long study has shown that metformin reduces the effect of ageing. Using a wide array of ageing indicators, the researchers found that metformin resulted in about six year regression in brain ageing. They reported their findings in Cell.
Prior research and anectodal evidence suggested that metformin had an anti-ageing effect. Given to flies, worms and rodents, the drug showed evidence of rejuvenation. People taking metformin also reported feeling younger the longer they took it for.
In a rigorous 40-month study, the researchers gave metformin to 12 elderly male cynomolgus macaques and 18 other cynomolgus monkeys the drug daily. They were aged 13–16 years, equivalent to 40–50 in human years. A control group was used, as well as middle-aged and younger controls to account for ageing effects.
The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin’s influence on delaying age-related phenotypes at the organismal level.
Tissue samples were taken at regular intervals, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin’s effects on ageing.
The results highlighted a significant slowing of aging indicators. A number of organs that seemed to benefit included the kidneys, lungs and the skin. The greatest effect was seen in the brain, however. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. In this case, treated monkeys had brain activity comparable to those six years younger.
The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. The researchers say that this work pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.
The researchers have also started a much larger phase 2 human trial, with 120 participants.
A team at Kumamoto University has made a ground-breaking discovery in the field of aging and inflammation. The research focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging. This cellular state, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.
The researchers found that ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, plays a critical role in activating SASP. This discovery was made using advanced sequencing and bioinformatics analyses on human fibroblasts, a type of cell found throughout the body. They demonstrated that blocking ACLY activity, either genetically or with inhibitors, significantly reduced the expression of inflammation-related genes in aging cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.
Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that DNA wraps around, allowing the chromatin reader BRD4 to activate inflammatory genes. By targeting the ACLY-BRD4 pathway, the researchers were able to suppress inflammation responses in aged mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.
This discovery opens new avenues for developing treatments that specifically target the harmful aspects of aging cells without removing them, offering a promising strategy for managing aging and age-related diseases. The research provides a stepping stone toward therapies that can control cellular aging, promoting longer, healthier lives.
Those who wish to live to 100 cannot rely on chance. Instead, it is essential to keep biomarkers associated with ageing and disease in check. By the age of 60, it may already be too late.
Text by: Maja Lundbäck, first published in Medical Science No 3 2024
Swedes are increasingly living to older ages. Thirty years ago, 85-90- year-olds were rare, but now the majority reach that age ‒ and two percent even get to see 100 candles on their birthday cake.
“Centenarians are the age group that is increasing the most now,” says Karin Modig, Associate Professor at the Institute of Environmental Medicine at Karolinska Institutet, who researches ageing and health.
In a study published in the journal GeroScience, she and her colleagues show that it is possible to predict who has the greatest chance of becoming very old already during early ageing. The study is based on approximately 44 000 Swedes who underwent health examinations between 1985 and 1996, aged between 64 and 99. Of these, 1224 individuals lived to 100.
“The results suggest that becoming very old is not solely a matter of chance; it also seems to be linked to lifestyle,” says Karin Modig.
Known biomarkers
By looking at known biomarkers previously associated with ageing and disease, the researchers found that the centenarians had better health than their peers already in their 60s. All but two of twelve biomarkers examined could be linked to increased chances of reaching 100 years. Low iron levels reduce the chance, as does low total cholesterol, which can be a marker of disease processes in the body.
Four of the biomarkers stood out as particularly important: creatinine levels, which indicate kidneys health, were almost always normal at age 60 in those who lived to 100. The same was true for liver markers and uric acid levels, a marker for inflammatory processes. Individuals with the lowest uric acid levels had a four percent chance of living to 100, while those with the highest levels had a 1.5 percent chance. Blood sugar levels were also rarely above 6.5mmol/litrw.
The results suggest that it may be possible to increase one’s chances of living to 100 by changing your lifestyle, she believes.
“At the same time, life is not about living according to an algorithm; everyone must find their own balance between risk factors and health factors,’ she says.
A new study has revealed that common breast cancer treatments, including chemotherapy, radiation, and surgery, may accelerate the biological aging process in breast cancer survivors. The findings, published in the Journal of the National Cancer Institute, show that markers of cellular aging, such as DNA damage response, cellular senescence, and inflammatory pathways, significantly increased in all breast cancer survivors, regardless of the type of treatment received. This suggests that the impact of breast cancer treatments on the body is more extensive than previously thought.
“For the first time, we’re showing that the signals we once thought were driven by chemotherapy are also present in women undergoing radiation and surgery,” said study lead author Judith Carroll, an associate professor of psychiatry and biobehavioural sciences at UCLA. “While we expected to see increased gene expression linked to biological aging in women who received chemotherapy, we were surprised to find similar changes in those who only underwent radiation or surgery.”
Advances in cancer therapies have greatly improved survival rates, with an estimated 4 million breast cancer survivors in the US today and over 6 million expected by 2040. However, breast cancer is linked to accelerated aging, impacting physical abilities, independence, and lifespan. Biological aging processes, which drive conditions like fatigue, cognitive decline, frailty, and cardiovascular disease, appear to be a major factor. Evidence suggests that cancer treatments, like chemotherapy, can increase the risk of earlier onset of these aging-related conditions, making it crucial to understand the specific pathways involved to better target and manage them.
To examine how gene expression related to aging changes over time in women diagnosed with breast cancer, the team conducted a two-year longitudinal study that tracked women undergoing breast cancer treatment prior to receiving treatment and again following treatment to see how their biological aging markers evolved.
The team tracked the gene expression in their blood cells using RNA sequencing, focusing on markers that signal biological aging, including a process known as cellular senescence, which is when cells stop dividing but don’t die. These so-called “zombie cells” accumulate over time and can release harmful substances that damage nearby healthy cells, contributing to aging and inflammation.
The data was then analysed using statistical models to help identify aging-related changes.
The team found that regardless of treatment type there was an increase in expression of genes that track cellular processes involved in biological aging. Specifically, genes that capture cellular senescence and the inflammatory signal from these cells, indicating that their immune cells were aging faster than normal.
They also saw increases in DNA damage response genes, which are genes that are expressed when there is DNA damage. Although chemotherapy did have a slightly different pattern, similar to what others have shown, they also noted changes in women who did not receive chemotherapy.
“The results suggest women who receive treatment for breast cancer have a pattern of gene expression that indicates increased DNA damage and inflammation, which could be important targets for recovering from cancer and having a better quality of life in survivorship,” said senior author of the study Julienne Bower(Link opens in new window), professor of psychology in the UCLA College and psychiatry and biobehavioural sciences and member of the UCLA Health Jonsson Comprehensive Cancer Center.
“We’ve only just begun to understand the long-term consequences of cancer therapy and these findings are a critical step toward understanding the biological pathways that drive many post-treatment symptoms in breast cancer survivors,” added Carroll. “Our goal is to find ways to improve survivorship, not just in terms of years lived, but also in quality of life and overall health.”
The team is now exploring a new biomarker that measures a woman’s biological age and the pace at which she is aging. This could help determine whether the aging signals detected during cancer treatment have a long-term effect on biological age. The team plans to investigate factors that may influence this, with a focus on protective behaviours such as exercise, stress management and healthy sleep patterns.
Muscle activation in people suffering from hip osteoarthritis might be a case of ‘mind over matter’, new research from Edith Cowan University (ECU) has shown.
Research undertaken by ECU post-doctoral research fellow Dr Myles Murphy investigated muscle function in people with hip osteoarthritis and found that these patients were unable to activate their muscles as efficiently. The findings are published in Sports Medicine and Health Science.
“Previous research has well established that the degree to which a joint degenerates is not directly related to the amount of pain a person with arthritis will experience. In fact, the stronger your muscles are, the more protected your joint is, and the less pain you will experience.
“Our research has shown that people with hip osteoarthritis were unable to activate their muscles as efficiently, irrespective of strength.”
As part of this research, Dr Murphy and his team studied the brain function of people with hip arthritis, finding that the mind played an enormous part in this equation.
“Basically, people with hip arthritis are unable to activate their muscles properly because the brain is actively putting on the brake to stop them from using the muscle. We don’t know why that is, yet. But the brain seems to really be hampering the progress of rehabilitation and the muscles to protect the joint,” Dr Murphy said.
“We suspect that it is a short-term, protective response gone wrong. Unlike a rolled ankle or a hurt knee, chronic pain like osteoarthritis tends to hang around for a long time. Instead of being a protective response in the short term, the brain’s protective response becomes a really problematic and maladaptive response in the long term.”
Hip osteoarthritis is more prevalent in people over the age of 45, and women are much more like to develop the condition. People who have reported previous joint damage, from a sports injury or accident, are more likely to present with hip osteoarthritis, as are those with joint abnormalities, such as developmental dysplasia of the hip.
People living with hip arthritis often presents with different walking patterns than those without and could struggle with everyday activities like getting out of a chair, or vehicle.
“The impact on their daily lives is the biggest burden of osteoarthritis. The condition also results in substantial time-loss from work, and is associated with a high economic cost,” Dr Murphy said.
“The level of disability for normal activity within our study cohort was about 25%, compared to the 0% reported in our healthy control group.”
Dr Murphy is currently investigating novel ways in which to overcome this automatic muscle inhibition to effectively rehabilitate patients.
In the meantime, those living with hip osteoarthritis have been urged to continue strength training and to work with a qualified physiotherapist or exercise physiologist.
“You will need to work quite hard to build the strength in those muscles, but it can be done. There is no quick fix. Staying strong is something that people with hip osteoarthritis will need to actively keep working on,” he said.
Life expectancy increased dramatically over the 19th and 20th centuries, thanks to improvements such as healthier diets and medical advances. But after nearly doubling over the course of the 20th century, the rate of increase has slowed considerably in the last three decades, according to a new study led by the University of Illinois Chicago.
Despite frequent breakthroughs in medicine and public health, life expectancy at birth in the world’s longest-living populations has increased only an average of six and a half years since 1990, the analysis found. That rate of improvement falls far short of some scientists’ expectations that life expectancy would increase at an accelerated pace in this century and that most people born today will live past 100 years.
The Nature Aging paper offers new evidence that humans are approaching a biologically based limit to life. The biggest boosts to longevity have already occurred through successful efforts to combat disease, said lead author S. Jay Olshansky of the UIC School of Public Health. That leaves the damaging effects of aging as the main obstacle to further extension.
“Most people alive today at older ages are living on time that was manufactured by medicine,” said Olshansky, a professor of epidemiology and biostatistics. “But these medical Band-Aids are producing fewer years of life even though they’re occurring at an accelerated pace, implying that the period of rapid increases in life expectancy is now documented to be over.”
That also means extending life expectancy even more by reducing disease could be harmful, if those additional years aren’t healthy years, Olshansky added. “We should now shift our focus to efforts that slow aging and extend healthspan,” he said. Healthspan is a relatively new metric that measures the number of years a person is healthy, not just alive.
Life expectancy increased rapidly through the 19th century and first half of the 20th century. In 1990, some scientists predicted those rapid gains would continue, leading to “radical life extension.” But a new analysis proposes that we may be nearing the limit of human longevity. (Strategic Marketing and Communications / UIC)
The analysis, conducted with researchers from the University of Hawaii, Harvard and UCLA, is the latest chapter in a three-decade debate over the potential limits of human longevity.
In 1990, Olshansky published a paper in Science that argued humans were approaching a ceiling for life expectancy of around 85 years of age and that the most significant gains had already been made. Others predicted that advances in medicine and public health would accelerate 20th-century trends upward into the 21st century.
Thirty-four years later, the evidence reported in the 2024 Nature Aging study supports the idea that life expectancy gains will continue to slow as more people become exposed to the detrimental and immutable effects of aging. The study looked at data from the eight longest-living countries and Hong Kong, as well as the United States – one of only a handful of countries that has seen a decrease in life expectancy in the period studied.
“Our result overturns the conventional wisdom that the natural longevity endowment for our species is somewhere on the horizon ahead of us – a life expectancy beyond where we are today,” Olshansky said. “Instead, it’s behind us – somewhere in the 30- to 60-year range. We’ve now proven that modern medicine is yielding incrementally smaller improvements in longevity even though medical advances are occurring at breakneck speed.”
While more people may reach 100 years and beyond in this century, those cases will remain outliers that won’t move average life expectancy significantly higher, Olshansky said.
That conclusion pushes back against products and industries, such as insurance and wealth-management businesses, which increasingly make calculations based on assumptions that most people will live to be 100.
“This is profoundly bad advice because only a small percentage of the population will live that long in this century,” Olshansky said.
But the finding doesn’t rule out that medicine and science can produce further benefits, he said. There may be more immediate potential in improving quality of life at older ages instead of extending life, the authors argue. More investment should be made in geroscience – the biology of aging, which may hold the seeds of the next wave of health and life extension.
“This is a glass ceiling, not a brick wall,” Olshansky said. “There’s plenty of room for improvement: for reducing risk factors, working to eliminate disparities and encouraging people to adopt healthier lifestyles – all of which can enable people to live longer and healthier. We can push through this glass health and longevity ceiling with geroscience and efforts to slow the effects of aging.”
When older people lose their balance, they often struggle to recall the circumstances, making studying this phenomenon challenging. Now, a Virginia Tech study using wrist-worn voice recorders concludes that voice recorders are effective at capturing the circumstances and context in which they lost their balance and potentially fell, without relying on recall later. The findings were recently published in the Journal of American Geriatrics Society.
The study, led by Michael Madigan in the College of Engineering, builds on years of his own foundational work and prior research conducted by the University of Michigan Medical School. “In the past, researchers would ask participants to recall what they were doing when they lost their balance, but memory can be unreliable,” said Madigan. “With this new method, participants record their experiences immediately after an incident, providing much more accurate and detailed information.”
Real-world insight
In this study, 30 participants, who averaged around 72 years of age, wore voice recorders on their wrists over the course of three weeks, and in the event of balance loss, turned them on to record answers to these key questions:
When and where did the balance loss occur?
What were they doing at the time?
How did they attempt to regain their balance – did they grab a railing, take steps, or sit down?
Why do they think they lost their balance?
Did they fall?
This immediate, self-reported data was analysed by Madigan and his team. Instead of waiting to meet with researchers after losing their balance, participants could reflect on what happened in the moment.
“We’re trying to better understand the circumstances in which people lose their balance,” Madigan said. “This process doesn’t require people to think back weeks or months to an incident, especially when memory can be unreliable.”
Participant experience
Maria Moll, a retired epidemiologist and study participant, found the research particularly meaningful, especially as someone in her 70s who remains physically active. After a friend experienced a fall, Moll became more interested in contributing to balance-loss prevention research.
“I’ve always been interested in physical fitness and balance, especially as I age,” said Moll. “This study made me more mindful of my movements, particularly during more challenging activities like hiking.”
The future of real-world data collection
Looking ahead, the team plans to expand the study to larger groups and combine the data with other lab-based measurements. By doing so, they hope to identify individuals who are most at risk of balance loss and develop strategies to proactively address those risks.
“We want to give clinicians the tools to intervene before a fall occurs,” said Madigan. “This method can provide more reliable, detailed information that helps us understand not just how people lose their balance, but why.”
As we celebrate Carer’s Week, an annual campaign recognising the invaluable work of caregivers, it’s essential to highlight the critical role they play in supporting the elderly and their families. In South Africa, the growing number of elderly individuals has created a pressing need for qualified caregivers.
Given the deep-rooted relationships between many domestic helpers and their employers, formally training these helpers to become specialised caregivers presents a promising solution. This approach not only ensures consistent care but also respects the deep connection between employer and helper, facilitating a smooth transition into a new phase of support and companionship.
Through specialised training, domestic workers can acquire the necessary qualification to provide professional elderly care within a three-month timeframe, while also enhancing their long-term career prospects.
Setting the stage for specialised care In South Africa, the Older Persons Act is clear that caregivers for the elderly must possess formal qualifications to ensure the provision of quality care. Temporary Employment Services (TES) offer a practical solution to this growing need, providing training and up-skilling of helpers to become qualified caregivers. Through focused instruction and hands-on learning, helpers gain formal proficiency in addressing the unique needs of the elderly, including wound care, palliative care, medication management, and mental health support.
The benefits of training domestic helpers Investing in training toward a formal qualification for domestic helpers has broader implications beyond immediate caregiving. For the helpers, it enhances their job prospects and ensures their continued employment security. Importantly, it equips them with the skills needed to navigate the changing terrain of elder care with assurance and proficiency.
In this way, empowering domestic helpers with specialised skills addresses the growing demand for quality elder care while contributing to the professional development and well-being of a dedicated workforce capable of caring for society’s most vulnerable.
The importance of trust and training The combination of trust and training serves as a cornerstone in elder care. The deep-rooted relationships between domestic helpers and their employers provide a foundation of trust and understanding, facilitating effective communication and collaboration.
When coupled with specialised training, these relationships become even more valuable, ensuring that the elderly receive personalised and compassionate care from individuals who genuinely care about their well-being.
TES providers can play a vital role in facilitating this transition, providing the necessary training and support to equip domestic helpers with the skills and knowledge required to become competent caregivers. Accredited training programs ensure that helpers are equipped to handle the challenges and responsibilities associated with elder care.
Benefits for the elderly and their families Beyond the immediate benefits, investing in training for domestic helpers can also contribute to the overall well-being of the elderly population. When the elderly receive care from trusted individuals who are familiar with meeting their specific needs, they are more likely to experience improved quality of life, reduced stress, and increased feelings of security and belonging. This can have a positive impact on their physical and mental health, leading to better overall outcomes.
As the elderly population grows, demand for quality elder care services will only increase. By empowering domestic helpers to take on caregiver roles, it is possible to meet this demand and reduce the strain on families who may be struggling to balance their own responsibilities with the needs of caring for their elderly loved ones.
Benefits for the caregiver and community In addition to the benefits for the elderly and their families, training domestic helpers for specialised elderly care can also have a positive impact on the broader community. Investing in the professional development of domestic helpers contributes to the growth and development of a skilled workforce. This can have long-term economic benefits for the country, as it can help to create jobs and boost the economy.
Training as a caregiver and receiving a formal qualification offers numerous benefits for domestic workers. This training enhances their job security, increases their earning potential, develops new skills, and helps to provide a sense of personal satisfaction and fulfilment. A caregiver qualification can open doors to a wider range of job opportunities, improve career prospects, and provide extensive opportunities for overseas employment.
A care transition that makes sense for everyone Empowering domestic helpers for specialised elderly care is a win-win situation. It addresses the growing demand for quality elder care, ensures continuity of care for the elderly, and provides opportunities for professional advancement for domestic helpers. As South Africa’s population ages, training domestic helpers to become specialised caregivers is a practical and effective approach to addressing the growing need for quality elder care.
This initiative not only benefits the elderly and their families but also empowers domestic workers and contributes to the development of a skilled and qualified caregiving workforce. By recognising the value of caregivers during Carer’s Week, we can highlight the importance of investing in their training and support.
Photo by Mikhail Nilov: https://www.pexels.com/photo/a-couple-doing-yoga-at-home-7500701/
Flexibility exercises are often included in the exercise regimens of athletes and exercisers. New research in the Scandinavian Journal of Medicine & Science in Sports suggests that levels of flexibility may affect survival in middle-aged individuals.
After analysing data on 3,139 people (66% men) aged 46–65 years, investigators obtained a body flexibility score, termed Flexindex. This score was derived from a combination of the passive range of motion in 20 movements (each scored 0–4) involving 7 different joints, resulting in a score range of 0–80.
Flexindex was 35% higher in women compared with men. During an average follow-up of 12.9 years, 302 individuals (9.6%) comprising 224 men and 78 women died. Flexindex exhibited an inverse relationship with mortality risk and was nearly 10% higher for survivors compared with non-survivors in both men and women.
After taking age, body mass index, and health status into account, men and women with a low Flexindex had a 1.87- and 4.78-times higher risk of dying, respectively, than those with a high Flexindex.
“Being aerobically fit and strong and having good balance have been previously associated with low mortality. We were able to show that reduced body flexibility is also related to poor survival in middle-aged men and women,” said corresponding author Claudio Gil S. Araújo, MD, PhD, of the Exercise Medicine Clinic – CLINIMEX, in Rio de Janeiro, Brazil.
He added that as flexibility tends to decrease with aging, it may be worth paying more attention to flexibility exercises and routinely including assessments of body flexibility as part of all health-related physical fitness evaluations.
Researchers from the Center for Healthy Aging, Department of Cellular and Molecular Medicine at the University of Copenhagen have made a breakthrough in lifespan research. They have discovered that a particular protein known as OSER1 has a great influence on longevity.
”We identified this protein that can extend longevity. It is a novel pro-longevity factor, and it is a protein that exists in various animals, such as fruit flies, nematodes, silkworms, and in humans,” says Professor Lene Juel Rasmussen, senior author behind the new study.
Because the protein is present in various animals, the researchers conclude that new results also apply to humans:
”We identified a protein commonly present in different animal models and humans. We screened the proteins and linked the data from the animals to the human cohort also used in the study. This allows us to understand whether it is translatable into humans or not,” says Zhiquan Li, who is a first author behind the new study and adds:
“If the gene only exists in animal models, it can be hard to translate to human health, which is why we, in the beginning, screened the potential longevity proteins that exist in many organisms, including humans. Because at the end of the day we are interested in identifying human longevity genes for possible interventions and drug discoveries.”
Paves the way for new treatment
The researchers discovered OSER1 when they studied a larger group of proteins regulated by the major transcription factor FOXO, known as a longevity regulatory hub.
“We found 10 genes that, when – we manipulated their expression – longevity changed. We decided to focus on one of these genes that affected longevity most, called the OSER1 gene,” says Zhiquan Li.
When a gene is associated with shorter a life span, the risk of premature aging and age-associated diseases increases. Therefore, knowledge of how OSER1 functions in the cells and preclinical animal models is vital to our overall knowledge of human aging and human health in general.
“We are currently focused on uncovering the role of OSER1 in humans, but the lack of existing literature presents a challenge, as very little has been published on this topic to date. This study is the first to demonstrate that OSER1 is a significant regulator of aging and longevity. In the future, we hope to provide insights into the specific age-related diseases and aging processes that OSER1 influences,” says Zhiquan Li.
The researchers also hope that the identification and characterization of OSER1 will provide new drug targets for age-related diseases such as metabolic diseases, cardiovascular and neuro degenerative diseases.
“Thus, the discovery of this new pro-longevity factor allows us to understand longevity in humans better,” says Zhiquan Li.
