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IL-17 protein identified as playing central role in skin ageing

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Wrinkles are a natural part of ageing. But few of us welcome their appearance.

Whilst we may be prepared to embrace the wisdom and experience that comes with age, the same can’t be said of those telltale lines, creases, furrows and folds that so visibly announce to the world that our salad days are behind us.

Such is our horror at quite literally being faced with a face full of crow’s feet and worry lines, that a multi-billion dollar industry has grown up pandering to our frantic attempts to turn back time.

The global anti-ageing market is estimated to be worth more than $60bn US dollars. As society becomes increasingly more beauty-conscious, the market for anti-ageing and skin-changing products is projected to reach a staggering $93bn by 2027.

But a new study conducted by a team of scientists from the Institute for Research in Biomedicine (IRB) and the National Center for Genomic Analysis (CNAG), both in Barcelona, has now identified the protein that plays a key role in skin ageing – opening up the possibility of new therapies being developed targeted at improving skin health.

The study published in the journal Nature Aging and led by Dr Guiomar Solanas and Dr Salvador Aznar Benitah, both of IRB Barcelona, and Dr Holger Heyn at CNAG, reveals that blocking the function of IL-17 delays the appearance of age-related features in the skin.

Skin ageing is characterised by a series of structural and functional changes that gradually contribute to the deterioration and fragility associated with age. Aged skin has a reduced capacity to regenerate, poor healing ability, and diminished barrier function.

Dr Benitah, who is head of the Stem Cells and Cancer laboratory at IRB Barcelona, said: “Our results show that IL-17 is involved in various functions related to ageing. We have observed that blocking the function of this protein slows down the appearance of various deficiencies associated with ageing skin.

“This discovery opens up new possibilities for treating some of the symptoms or facilitating skin recovery after surgery, for example.”

Dr Heyn, head of the Single Cell Genomics laboratory at CNAG, added: “Single cell sequencing has allowed us to dive deep into the complexity of cell types and states forming the skin and how these change during lifespan.

“We did not only find differences in the composition of aged skin, but also changes in cell activity states. Particularly immune cells showed specific age-related profiles, which we could pinpoint by analysing thousands of individual cells one at a time.”

In addition to a wide variety of epithelial cells, hair follicle cells, and other components, the skin is also home to immune cells, which play a crucial role in preventing infection and protecting against different damages.

The groundbreaking researh describes how, during ageing, the presence of some of these immune cells, namely gamma delta T cells, innate lymphoid cells, and CD4+ T cells, significantly increases in the skin. These same cells also start expressing very high levels of the pro-inflammatory cytokine IL-17.

Dr Paloma Solá, first author of the paper, together with Dr Elisabetta Mereu, who is now a researcher at the Josep Carreras Leukaemia Research Institute in Barcelona, said: “Ageing is associated with mild but persistent inflammation and, in the skin, this is characterised by a significant increase in IL-17, which causes skin deterioration.”

Previous studies had described that IL-17 is related to some autoimmune skin diseases, such as psoriasis, and there are existing treatments that block this protein.

The team of researchers studied the response of various aspects to blocking IL-17 activity, including hair follicle growth, transepidermal water loss, wound healing, and genetic markers of ageing.

These four parameters showed an improvement after treatment, as the acquisition of these ageing traits was significantly delayed.

Dr Solanas, associate researcher at IRB Barcelona, commented: “IL-17 protein is essential for vital body functions, such as defence against microbes and wound healing, so permanently blocking it would not be an option. What we have observed is that its temporary inhibition offers benefits that could be of interest at a therapeutic level.”

Future work by the researchers will focus on clarifying the ageing processes that are related to inflammatory states in the skin and how these are linked to IL-17.

The team will also address whether IL-17 is involved in the ageing and deterioration of other tissues and organs.

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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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