LongeCityNews Last Updated: 25 December 2024 - 12:28 PM

Stroke is the blockage or rupture of a blood vessel in the brain, leading to significant damage to brain tissue and consequent loss of function. Beyond the immediate harm it is now well known that stroke leads to accelerated cognitive decline over time following the event. This is perhaps mediated by increased inflammation leading to degeneration of the thalamus, a central node in communication between brain regions. This accelerated brain-wide neurodegeneration caused by stroke is not as well understood as the mechanisms driving the immediate damage and aftermath of a stroke, however.

In today's open access paper, researchers consider an increased burden of cellular senescence in the brain resulting from a stroke as a possible contributing factor to further declining function over time. Senescent cells cease to replicate and secrete a pro-inflammatory mix of signals. In the short term the presence of senescent cells and their signaling helps to coordinate regeneration from injury, to the degree that the brain is capable of such regeneration. Over the long term, however, the sustained inflammatory signaling generated by senescent cells is disruptive to tissue structure and function. In this way, lingering senescent cells are a cause of degenerative aging, in the brain and elsewhere in the body.

Cellular senescence as a key contributor to secondary neurodegeneration in traumatic brain injury and stroke

Traumatic brain injury (TBI) and stroke pose major health challenges, impacting millions of individuals globally. Once considered solely acute events, these neurological conditions are now recognized as enduring pathological processes with long-term consequences, including an increased susceptibility to neurodegeneration. However, effective strategies to counteract their devastating consequences are still lacking.

Cellular senescence, marked by irreversible cell-cycle arrest, is emerging as a crucial factor in various neurodegenerative diseases. Recent research further reveals that cellular senescence may be a potential driver for secondary neurodegeneration following brain injury. This review offers critical insights into the role of cellular senescence in secondary neurodegeneration following TBI and stroke. A growing body of evidence underscores a strong connection between cellular senescence, inflammation, and neurodegeneration. Notably, senescent cells, a common pathological feature, are present in the brain after TBI or stroke.

Although the precise vulnerability of different cell types to senescence and their interactions remain underexplored, the targeted elimination of these cells has yielded promising preliminary results in mitigating brain injury-induced neuronal degeneration. These findings highlight a novel therapeutic target for addressing secondary neurodegeneration following brain insult. From a translational standpoint, further rigorous investigation into the safety and efficacy of senolytic agents is imperative, as it holds the potential to open new avenues for managing the long-term consequences of brain injury.

The research noted here, showing that innate immune responses are regulated by circadian rhythm, is interesting in the context of aging. Aging is characterized by both a complex disruption of circadian rhythm, alongside a growing state of constant inflammation, some of which is generated by maldaptive innnate immune reactions to the molecular damage that becomes more prevalent with age, such as mislocalized mitochondrial DNA resulting from mitochondrial dysfunction. To what degree is the chronic inflammation of aging made worse by issues with regulation of circadian rhythm? This is a question yet to be definitively answered.

New research the link between the immune system and the body's circadian rhythms often referred to as the body clock. Macrophages, immune cells that detect and respond to harmful substances, are able to trigger inflammation as a defence mechanism by assembling large complexes known as inflammasomes. Inflammasomes could be compared to 'smoke detectors' that will then alert the immune system of danger.

Activation of an inflammasome called NLRP3 was not found to be constant throughout the day but was regulated by the body's 24-hour circadian clock. This daily rhythm determines when macrophages are most efficient at detecting threats and when their energy levels peak to mount a response. The research also highlights a key role for mitochondria, the cell's energy producers, in driving these daily changes in immune activity. The study has significant implications for understanding and treating inflammatory diseases, such as arthritis, where overactive inflammasomes play a key role. Symptoms of such diseases often worsen in the morning, something this research may help explain.

Link: https://www.rcsi.com/dublin/news-and-events/news/news-article/2024/12/rcsi-research-reveals-how-the-body-clock-regulates-inflammation

Early multicellular organisms must have fairly quickly evolved mechanisms to eliminate damaged or otherwise unfit cells during development. Some of those mechanisms continue throughout life. We might expect to find that genes involved in these elimination processes affect the pace of aging, as should anything that reduces damage and increases robustness. Here researchers show that the known longevity-associated gene FOXO3 is an important player in the processes of cell competition that operate during early development, removing unfit cells to ensure that viable, functional tissues are generated. One might look at analogous work on the role of azot in fruit flies, also a longevity-associated gene involved in elimination of unfit cells.

In this study, we identified a previously unknown universal cell competition marker in vertebrates and elucidated the novel roles and mechanisms of physiological cell competition during organogenesis - the Shh-unfitness-driven cell competition. In zebrafish spinal cord and muscle development regulated by Shh morphogen gradients, unfit cells with abnormal Shh activity spontaneously appear and distort the morphogen gradient. Subsequently, unfit cells alter membrane N-cadherin levels, activate the Smad-Foxo3-ROS axis, and undergo apoptosis through communication with neighbouring normal cells. In zebrafish and mouse, Foxo3 is upregulated in cells with abnormal morphogen signalling and in various less-fit cells, which are eliminated through cell competition. Thus, Foxo3 can be a common marker of cell competition in vertebrates.

Artificially introduced cells with abnormal Myc or Axin2 activity trigger competitive communication with neighbouring normal cells in developing mouse organs (i.e. the heart, skin, and brain). These facts suggest that developing tissues can eliminate unfit cells through cell competition. However, whether unfit cells are generated and drive cell competition during physiological organogenesis is poorly understood. This is partly due to the inherent difficulty in capturing spontaneously arising abnormal cells. In our zebrafish model, which is well-suited for imaging analyses, we previously captured the emergence of unfit cells during embryogenesis. In this study, we visualised abnormal cell appearance and endogenous cell competition in vertebrate organogenesis and elucidated their regulatory mechanisms. Furthermore, we demonstrated that eliminating these unfit cells is essential for proper organogenesis. Thus, we have revealed the physiological significance of cell competition during organogenesis.

Link: https://doi.org/10.1038/s41467-024-55108-x

The nights are the longest of the year, the holidays are drawing near, and we are back with a festive edition of the Lifespan.io editorial. This time, we bring you some of this year’s highlights and talk about what the future holds for our content.

Lifespan.io and SENS Research Foundation merge

Regulars will recall that Lifespan Extension Advocacy Foundation and SENS Research Foundation merged in October. We are now the Longevity Research Institute (LRI), an organization focused on rejuvenation biotechnology research and news.

The two organizations have combined to pursue the goal of healthier and longer lives for all. Keith Comito, President of the Board, had this to say about the merge:

“Lifespan.io and SRF have shared a rich legacy in the battle against age-related diseases, driven by passion and purpose in both advocacy and research. Today, we unite these powerful forces to forge an organization uniquely equipped to identify and advance the most transformative projects in our field. Together with you, the Lifespan Research Institute will work to create a future where vitality and long-lasting health are within reach for everyone.”

Lifespan.io will continue to bring you the latest longevity news from the same website, so there’s no need to change your bookmarks!

Celebrating a decade of independent non-profit journalism

Lifespan.io has been one of the top sources for non-profit aging research news for the last decade. Here are some of the things we have achieved:

• 10 years of independent journalism.
• 270 news articles published this year so far!
• 160 longevity topics and growing.
• 147 leading researchers interviewed since 2014.

Not bad for a small non-profit organization that started with a handful of people, right? We think so, and it has been an awesome experience supporting the aging research field over this last decade.

This field is a very unique one, and it is both a challenge and privilege to focus our journalism on it. Since we started 10 years ago, there has been a significant change in the field. This field of research, which a significant part of the public had considered to be fringe, is steadily growing in credibility and respect.

Hucksters peddling unscientific nonsense continue to harm our field’s reputation, but things are starting to improve. In recent years, real science has started to take the spotlight.

Many rejuvenation treatments are in or near human trials, and the science is gaining traction as its credibility increases. While there is still much work to be done, there is reason for optimism and hope that longer, healthier lives are something that we can achieve in the near future.

Independent journalism is at risk

Dear readers, I am Steve Hill, Editor-in-Chief of Lifespan.io, and I need to tell you about the crisis happening right now in journalism.

The anti-competitive practices of big tech firms are an existential threat to independent journalism. Companies like Google and Meta are effectively gatekeepers of online content, deciding what internet users see. While this has long been the case, the level of control they have is now extreme.

Facebook, Linkedin, X, and other social media are increasingly trying to keep users on their platforms. They have made social media into a walled garden: a place where external content is consumed without any benefits for its creators, such as independent journalists.

The emphasis on paying to be seen on social media, even by your own followers, has gotten completely out of hand. This hurts content creators who are struggling to be seen, doubly so for non-profit organizations like us.

Non-profit content makers like us are increasingly being pushed out of internet search results. This is in part thanks to sweeping changes that Google has made to its search algorithm.

The risks from AI-generated content are greater than ever before, too. Often, such AI content is filled with misinformation and cannot be a trusted source. On top of that, Google’s clumsy attempts to stem the tide of low-quality AI content with changes to its search algorithm has damaged many legit content creators too.

Finally, the use of AI search overlays means that content creators like us are effectively having our content stolen, repackaged, and served up by Google as their own work. All of this is done without any acknowledgement or reward for content creators’ efforts!

All of this means that it’s become harder to reach people and tell them about the amazing work happening in our field. It is absolutely vital, now more than ever before, for independent voices to be heard.

Why independent longevity journalism is important

We are an important voice for the aging and rejuvenation research field. Our ethics code of longevity journalism is what makes us stand out from our competitors and makes us a source of information you can trust.

Our non-profit status means thaat our news remains free from government and commercial influence and will always be free. This is because we believe in sharing knowledge and a world where science is not locked behind paywalls.

But, it’s like the old saying goes: “Use it or lose it!” Put simply, without the support of the community, we cannot continue to be your trusted source for longevity news. If you value independent journalism that isn’t motivated by profit, please consider supporting us this holiday season!

How you can support independent longevity journalism

If you like what we do and you want to help us to keep doing it, I would like to ask you to support us in one or more ways:

• Donate: No matter how big or small, every little bit helps us to keep creating content for you. Help us by making a donation today.
• Be a Hero: The most important way you can support our work is by becoming one of our monthly patrons: the Lifespan Heroes.
• Stay informed: Keep up to speed about what is happening in the exciting world of rejuvenation research by joining our monthly newsletter.
• Follow us: We are on Facebook, Instagram, Linkedin, and X.

With your support, independent journalism can continue to thrive, and we can keep bringing you the best in independent journalism covering aging, longevity, and rejuvenation.

Best wishes to you and your family for the holidays and a happy new year.

Now, on to more positive things as we take a look at this year’s top stories and future plans for content here on the news outlet.

Success in the lab for the Longevity Research Institute

2024 was a year to celebrate our organization’s success in the lab. Researchers at the Longevity Research Institute (LRI) published results in December showing they had achieved the expression of an essential mitochondrial gene in the nucleus and proper functioning of the protein.

This important research builds on years of work towards finding a solution to age-related mitochondrial dysfunction. The mitochondria are the power stations of our cells. Unfortunately, as we age, they get increasingly damaged and unable to function.

To combat this, LRI aims to make copies of the mitochondrial genes inside the safety of the cell nucleus. This research brings us another step closer to that final goal. If we can keep our mitochondria healthy and functional as we age, it could have big implications for our health and longevity.

“This work represents the culmination of more than a decade’s worth of effort to provide a genetic backup system for mitochondrial DNA in mammals, for which inherited mutations cause disease in nearly 1 in 200 people,” said Dr. E. Lillian Fishman, Director of Research and Education at LRI.

This line of research could help combat diseases such as age-related muscle loss, Parkinson’s, and Alzheimer’s. It might also be used to potentially treat mitochondrial diseases that cause seizures and blindness.

Top stories of 2024

It’s been a busy year packed with great stories, but as is customary for this time of year, here are some of the best ones from 2024.

I Dined with Bryan Johnson and Didn’t Die

Journalist Arkadi Mazin was invited to Bryan Johnson’s home for one of his famous “Don’t Die Dinners”.

Johnson has been hosting these dinners for a few years. His guests often include celebrities and key figures in longevity research and important figures in the longevity research field.

Johnson is a somewhat controversial figure in the longevity community. His efforts to improve his health and extend his life have sparked much discussion. In this interview, Arkadi delves into what drives him to do the things he does for longevity.

Whether his approach is right or wrong is a subjective opinion, and you may or may not agree with his methods. However, we believe you will enjoy this interview either way.

Have We Maxed Out on Life Expectancy Gains?

One research paper that seems to have ruffled quite a few feathers in the community suggested that radical life extension was all but impossible in this century.

Often, predictions like these are followed by a demonstration that the said impossible thing is in fact possible. The Wright Brothers are an example of that: they demonstrated that heavier-than-air flight was perfectly possible despite experts at the time saying it was not.

However, what seems to have escaped quite a few people about this paper was that Jay Olshanky and the other authors did not discount the possibility that radical life extension may be achieved if breakthroughs in rejuvenation biotechnology were to occur.

It really is the case that nature is not going to solve aging and that life expectancies are no longer rising as they have in previous decades. It says everything about what nature will do, but puts no limits on what we might achieve through science.

Mehmood Khan on Aging Policy and Collaboration

Recently, Arkadi did an interview with Dr. Mehmood Khan about aging policy and how reframing the goal of rejuvenation biotechnology might help to drive progress forward faster. Longevity apparently means something quite different to high-level policy makers than it might for most people.

To these policymakers, it isn’t about people living longer for the sake of living longer but about productivity. This is why we need people like Khan advocating for our field and being able to speak the language policymakers want to hear to unlock funding for longevity research.

As sad as it is that we need to argue for the right to live longer and healthier lives through science, this is the reality of things. We think this interview might be an interesting read and help you understand what we are up against when it comes to advocacy and making policy work for us, not against us.

AI in Longevity: The Reality Today

Lifespan.io journalist Maria Isabella brought us an overview of the role of AI in longevity research and how it is being used in healthcare today.

Patient data analysis is a currently popular use case for AI, and a number of companies are involved in this. AI isn’t without its potential issues though, and we take a look at some of these in this article.

We are planning to delve deeper into the emerging use of AI in relation to aging and rejuvenation research in the future, but for now, we think you should enjoy this high-level summary of the technology.

Peter Diamandis: “Stay Healthy, Anti-Aging Tech is Coming”

In August, Peter Diamandis shared his thoughts on the aging and rejuvenation field with Arkadi.

Diamandis is an influential figure in the aging and rejuvenation world. He is an entrepreneur and investor in several fields, including commercial space flight and rejuvenation biotechnology.

During this fascinating interview, he shares his insights into how to encourage high-net-worth investors to get into the longevity space and why it is such a challenge to do so.

While there are a number of challenges our field faces in both progressing the research and funding for that research, Diamandis offers an overall message of hope and positivity for the future that we think you will enjoy.

These are just some of the great articles Lifespan.io has published this year, and we hope you continue to enjoy reading more in 2025.

Future improvements to our content

Our commitment to bring you the best in independent journalism will continue in 2025. In fact, we are scaling up what we plan to offer in the new year in order to bring you even more quality content.

Earlier this year, we did an audience survey, and the results were amazing! We asked you what you wanted to see us focusing on, you told us, and we listened. So, for 2025, we are going to be exploring new and exciting content and bringing you more of the things you asked for.

• Based on your feedback, we are going to be publishing more interviews, op-eds (opinion pieces by leading external researchers), special reports, feature pieces, and more!
  • The ethics of launching a supplement based on your research (op-ed) – We’ll invite a leading expert to speak about the perils and positives of researchers who opt to launch supplements following their initial research. Is it ethical or harmful to perception and progress in the field?
  • The hype and reality of the field (op-ed) – While we should be committed to the defeat of aging, it is important to ensure we remain grounded and realistic. A leading expert (probably Matt K) will discuss the field in a sober and realistic manner.
  • The reality of AI in research (op-ed) – We’ll invite a leading expert to talk about how exactly AI is being used in the research setting, its potential, and its limitations. There is a lot of misconception around what AI is likely to achieve in the context of aging research, so it’s important to have a grounded discussion about it.
  • Reviewing progress in the field (review) – We’ll publish a high-level report on where we are in the context of achieving damage repair. We used to do a yearly report called “SENS – Where are we now?” This will be similar but with a wider Hallmarks of Aging focus to match our excellent Rejuvenation Roadmap.
• We will be exploring the world of longevity investment and business and taking deep dives into the things investors want to know about the field:
  • Lifespan prediction – We’ll look at capabilities of AI in this area, companies working in this field, actual technology, and why finance companies may be interested (spoiler: it’s medical and pension costs).
  • AI and Longevity – We’ll take a look at the reality of solutions and perspectives, including external expert commentary.
  • DeSci and longevity – How much funding has DeSci/crypto really generated? We’ll analyze the impact of DeSci on the field and asking the question: Has DeSci been a success or failure in driving progress? We’ll look at the biggest funding of the year, research, what has been learned, and what could be ahead in 2025 for DeSci.
  • Thinking of doing research? – We’ll discuss funding, including crypto, along with the reality of application procedures, including commentary from internal and external experts.
  • Economics of living longer – Are we ready? We’ll discuss infrastructure, finance, health and planning.
• Expanding the Rejuvenation Roadmap –  We aim to continue to grow the Rejuvenation Roadmap. We are currently tracking 224 rejuvenation biotech interventions and biomarkers, and we want to increase that to 300+ in the next year.

There is plenty to look forward to in the new year, and we hope you will continue to visit us for your aging research news. Finally, we wish you Happy Holidays from the Lifespan.io team!

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If you want to keep up with the latest research news, then feel free to join our newsletter. We will see you in the next editorial with more updates and news on what our new organization has been doing to defeat age-related diseases.