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Have scientists finally found the cure for ageing?

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Cleopatra is said to have favoured asses’ milk, the ancient Greeks olive oil and yoghurt, Elizabethan women slices of raw meat, the Georgians mature wine, and the Victorians honey, oatmeal and egg yolks.

The above may read like a catalogue of fashionable foods from an historical grocery list or the latest fad diet. But in their day these mixed bag of ingredients were considered to be cutting-edge anti-ageing cures.

The fight against wrinkles and lines has been preoccupying humans if not quite from the dawn of time, from at least 2500BC when the people of the Indus Valley Civilisation are known to have developed powders and herbal remedies to improve not just their complexion but prevent thinning tresses and the appearance of grey hair.

The desire to turn back the human biological clock and stay forever young has become the  modern day Holy Grail. According to industry research company IMARC Group, the global anti-ageing market was worth US $67.2bn in 2022. That figure is predicted to swell to a staggering US $98.6bn by 2028 on the back of a rising awareness of the plethora of anti-ageing products now on the market, the increased consciousness among individuals about their physical appearance, and the growing popularity of non-surgical procedures and treatments designed to counter the process of becoming old.

Reversing or slowing down the effects of ageing isn’t just pre-occupying the beauty industry and the billions around the world slavishly buying into medical procedures and over-the-counter remedies promising to restore a youthful body and complexion.

Research scientists too are captivated with finding an answer to the centuries old question of how the brakes can be applied to ageing.

And not necessarily for the sake of our vanity. Ageing is the most debilitating problem humans face. Sadly, getting old can open a Pandora’s box of unpleasant health issues, from cancer to dementia, mobility problems, hearing loss, diabetes, pulmonary disease and depression.

According to the latest figures from the EU, 84.9% of all deaths in 2020 across European Union countries occurred in people over the age of 65. Of those, just over a third (35%) of deaths were caused by diseases of the circulatory system. Nearly one in three of these (11%) were as a result of ischaemic heart disease.

The second most common cause of death among elderly people was cancer at 20.5%.

But a growing number of scientists claim it doesn’t have to be like this and are seeking ways of rebooting the body.

According to João Pedro de Magalhães, a professor of Molecular Biogerontology in the Institute of Inflammation and Ageing at the University of Birmingham in the UK, most mechanistic explanations of ageing put forward that it’s caused by the accumulation of one or more forms of molecular damage.

But Professor Magalhães thinks otherwise. He believes ageing could be seen as an error in the software that guides how our bodies regulate themselves. In other words, ageing is a software design flaw, and to understand the process scientists need to decode human genetic software.

Professor Magalhães has been exploring the question of why ageing happens uniformly, when current models work on the assumption that we accumulate ‘damage’ randomly, and has recently had a review published on the subject in the open access scientific journal, Genome Biology.

“If we imagine that the human body is a bit like a computer, the paper suggests that ageing is not an accumulation of damage to the hardware, but a process driven by design flaws in the software, a radical departure from damage-based theories that until now have prevailed in ageing research,” he explained.

“Ageing is inherent to all human beings. It is widely thought that ageing occurs due to the accumulation of various forms of molecular damage. What if, however, ageing changes are not primarily a result of a build-up of stochastic, random damage but are rather a product of regulated processes?

“In other words, what if we age not because of inevitable damage to the hardware but rather because of the software, defined as the DNA code that orchestrates how a single cell develops into an adult organism? As a result, we could see ageing is an information problem.”

He suggests that medical interventions to combat ageing could be based on a faulty premise and needs to be reconsidered in light of the uniform, DNA-encoded nature of ageing.

Professor Magalhães compares the challenge of understanding ageing to how a computer system functions, likening cells and their components to computer hardware, and genetic information to software.

He argues that interventions akin to a computer restart, such as cell reprogramming, which is also known as epigenetic rejuvenation, could hold clues for future interventions to promote healthy ageing.

In addition, Professor Magalhães warns that existing treatments which work on the basis that ageing is an accumulation of cell damage over time, are unlikely to lead to broad positive impacts.

He said: “Seeing ageing as the outcome of ‘flaws’ in our software has important implications for studying and developing interventions for ageing. Traditional anti-ageing interventions targeting damage, like oxidative damage and telomere shortening, will have limited success.

“By contrast, ageing therapies will only be effective if targeting the software rather than the hardware. Seeing ageing as a programmed process would transform our perception of the ageing process with multiple and profound implications.”

Professor Magalhães believes understanding the biology of ageing would shed important light on the cause of age-related diseases. He said: “I suggest that design flaws in the developmental software program contribute to the development of many age-related diseases. Even cancer, which is largely due to molecular damage, is influenced by ageing processes.”

Professor Magalhães is not alone in his thinking. A 13-year study by researchers at Harvard University has also shown that the modification of gene expression can lead to cell ageing.

The study, published in the journal Cell, suggests it is the way DNA is governed that drives ageing.

Put simply. the Harvard study is suggesting that ageing doesn’t mean that cells are damaged and incapable of behaving like young cells, but that something has got lost in translation in their genetic make-up.

The researchers say that in theory, if epigenetic (the study of stable changes in cell function that do not involve alterations in the DNA sequence) interventions are used to get cells back on the right track, they can ‘remember’ how to be young and fully functioning again, effectively reversing the ageing process.

In the main experiment using mice, the scientists at Harvard mimicked breaks in chromosomes that cells experience every day in response to things such as breathing, exposure to sunlight and contact with certain chemicals.

They ensured these breaks did not occur in the coding regions of the DNA so mutations were prevented from occurring over time. The team noticed that the epigenome grew disorganised leading to more aged looks and behaviour.

Next, they delivered gene therapy to reverse the changes and found the organs and tissues had resumed their youthful state.

The paper’s senior author, David Sinclair, a professor of genetics in the Blavatnik Institute at Harvard Medical School and co-director of the Paul F Glenn Center for Biology of Aging Research, said: “It’s like rebooting a malfunctioning computer,” explaining that the therapy “set in motion an epigenetic programme that led cells to restore the epigenetic information they had when they were young. It’s a permanent reset.”

Dr Sinclair hopes the work inspires other scientists to study how to control ageing to prevent and eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty.

“These are all manifestations of ageing that we’ve been trying to treat with medicines when they arise, which is almost too late,” he said.

Co-first author Jae-Hyun Yang, a research fellow in genetics in the Sinclair lab. added: “We expect the findings will transform the way we view the process of ageing and the way we approach the treatment of diseases associated with ageing,”

The ultimate goal, Dr Sinclair  concluded, would be to address the root causes of ageing to extend human health span: the number of years that a person remains not just alive, but well.

Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But, Dr Sinclair said, scientists should think big and keep trying to achieve such dreams.

“We hope these results are seen as a turning point in our ability to control aging,” said Dr Sinclair. “This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will.

“We’re talking about taking someone who’s old or sick and making their whole body or a specific organ young again, so the disease goes away. It’s a big idea.”

 

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Tai chi outperforms conventional exercise for seniors

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New findings from 12 studies involving 2,901 participants have demonstrated that tai chi outperforms conventional exercise in improving mobility and balance in seniors.

While tai chi is understood to be beneficial for functional mobility and balance in older adults, such benefits are not well understood due to large variance in research study protocols and observations.

This new review and analysis has now shown that tai chi can induce greater improvement in functional mobility and balance in relatively healthy older adults compared to conventional exercise.

The findings showed the following performance results:

  • The time to complete 50-foot walking was 1.84 seconds faster. 
  • The time to maintain a one-leg stance was 6 seconds longer when eyes were open and 1.65 seconds longer when eyes were closed. 
  • Individuals improved their timed-up-and-go test performance by 0.18 points, indicating quicker standing, walking, and sitting.
  • Individuals taking the functional reach test showed significant improvement with a standardised mean difference of 0.7, suggesting a noteworthy positive impact on the ability to reach and perform daily activities.

Secondary analyses revealed that the use of tai chi with relatively short duration of less than 20 weeks, low total time of less than 24 total hours, and/or focusing on the Yang-style of this ancient form of Chinese martial arts were particularly beneficial for functional mobility and balance as compared to conventional exercise.

“This systematic literature review and meta-analysis are exciting because they provide strong evidence that tai chi is a more efficient strategy to improve functional mobility and balance in relatively healthy older adults, as compared to conventional exercise,” said Brad Manor, Ph.D., director of the Mobility and Falls Program at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, and associate professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center.

“This research suggests that tai chi should be carefully considered in future studies and routines of rehabilitative programs for balance and mobility in older adults,” said Bao Dapeng, professor at Beijing Sport University.

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New standards for biomarkers of ageing

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A paper has put forward a new framework for standardising the development and validation of biomarkers of ageing to better predict longevity and quality of life.

Led by Harvard researchers, the team has zeroed in on biomarkers of ageing using omic data from population-based studies. 

The team included ageing and longevity expert Alex Zhavoronkov, PhD, founder and CEO of AI-driven drug discovery company Insilico Medicine, and the findings appeared in Nature Medicine

Ageing is associated with a number of biological changes including increased molecular and cellular damage, however, researchers do not yet have a standardised means to evaluate and validate biomarkers related to ageing. 

In order to create those standards as well as actionable clinical tools, the team analysed population-based cohort studies built on omic data (data related to biological molecules which can include proteomics, transcriptomics, genomics, and epigenomics) of blood-based biomarkers of ageing. The researchers then compared the predictive strength of different biomarkers, including study design and data collection approaches, and looked at how these biomarkers presented in different populations. 

In order to better assess the impact of ageing using biomarkers, the researchers found that clinicians needed to expand their focus to consider not only mortality as an outcome, but also how biomarkers of aging are associated with numerous other health outcomes, including functional decline, frailty, chronic disease, and disability. They also call for the standardisation of omic data to improve reliability. 

“Omics and biomarkers harmonisation efforts, such as the Biolearn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics. 

Biolearn is an open-source project for biomarkers of aging and is helping to harmonise existing ageing biomarkers, unify public datasets, and provide computational methodologies.

The team also emphasised the importance of continued collaborations among research groups on “large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations”, and that further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.

“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of ageing,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. 

“We hope that our framework will help prioritise the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”

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Healthy aging research to receive $115 million

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Global non-profit Hevolution Foundation has announced $115 million in funding that makes up 49 new awards under its Geroscience Research Opportunities (HF-GRO) programme.  

As part of Hevolution’s mission to catalyse the healthspan scientific ecosystem and drive transformative breakthroughs in healthy aging, HF-GRO is funding promising pre-clinical research in aging biology and geroscience. 

Through this first wave of HF-GRO awards, Hevolution will invest up to $115 million in this first cohort of 49 selected projects over the next five years. Its second call for proposals under HF-GRO will be announced later this year, offering an additional $115 million to address the significant funding gaps in aging research.  

Dr. Felipe Sierra, Hevolution’s Chief Scientific Officer stated: “These 49 important research projects represent a significant step forward in deepening our understanding of healthy aging. Hevolution’s prime objective is to mobilise greater investment around uncovering the foundational mechanisms behind biological aging. 

“We are steadfast in our belief that by examining the root causes of aging, rather than solely focusing on its associated diseases, we can usher in a brighter future for humanity.” 

HF-GRO awardees include researchers at prestigious institutions across the United States, Canada, and Europe, including the U.S. National Institute on Aging, Brigham and Women’s Hospital, the Buck Institute, the Mayo Clinic, New York University, and the University of California San Francisco, among many others. 

The American Federation for Aging Research is providing programmatic support for the HF-GRO program, with grantees selected through a rigorous two-stage peer-review process involving 100 experts in aging biology and geroscience. 

Dr Berenice Benayoun, an HF-GRO grant recipient at the University of Southern California, stated: “I am extremely honored and excited that Hevolution selected our project for funding. This is a project close to my heart, which aims at understanding why and how the female and male innate immune aging differs. 

“This funding will support us as we start laying the foundation for a lasting improvement of women’s health throughout aging.” 

To date, Hevolution has committed approximately $250 million to transform the healthy aging sector, including the $40 million for specialised research and development in healthspan science recently announced at Hevolution’s Global Healthspan Summit. 

Hevolution is ramping up its investments to enable healthier aging for all and is now the second largest funder of aging biology research worldwide.  

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