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Hallmarks of Aging: Epigenetic Alterations – Article by Steve Hill

Hallmarks of Aging: Epigenetic Alterations – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses one of the hallmarks of aging – in this case, Epigenetic Alterations. It is part of a paper published in 2013. It divides aging into a number of distinct categories (“hallmarks”) of damage to explain how the aging process works and how it causes age-related diseases [1]. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                        ~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 18, 2017

What are epigenetic alterations?

The DNA in every one of our cells is identical, with only small variations, so why do our various organs and tissues look so different, and how do cells know what to become?

DNA is modified by the addition of epigenetic information that changes the pattern of gene expression in a cell, suppressing or enhancing the expression of certain genes in a cell as the situation demands. This is how a cell in the liver knows that it needs to develop into a liver cell; the epigenetic instructions make sure that it is given the right orders to become the correct cell type.

At a basic level, these epigenetic instructions make sure that the genes needed to develop into a liver cell are turned on, while the instructions specific to other types of cells are turned off. Imagine if a heart cell was given the wrong instructions and became a bone cell!

How epigenetic alterations accumulate

The aging process can cause alterations to our epigenome, which can lead to alterations in gene expression that can potentially change and ultimately compromise cell function. As an example, epigenetic alterations of the immune system can harm activation and suppress immune cells, thus causing our immune system to fail and leaving us vulnerable to pathogens.

Inflammation is implicated in epigenetic alterations, and studies show that caloric restriction slows the rate of these epigenetic changes [2]. Metabolism and epigenetic alterations are closely linked with inflammation, facilitating a feedback loop leading to ever-worsening epigenetic alterations. Alterations to gene expression patterns are an important driver of the aging process. These alterations involve changes to DNA methylation patterns, histone modification, transcriptional alterations (variance in gene expression) and remodeling of chromatin (a DNA support structure that assists or impedes its transcription).

In the cell, gene expression is activated by hypomethylation (a loss of methylation) or silenced by hypermethylation (an increase of methylation) at a gene location. The aging process causes changes that reduce or increase methylation at different gene locations throughout the body. For example, some tumour suppressor genes become hypermethylated during aging, meaning that they cease functioning, which increases the risk of cancer [3]. Post-translational modifications of histones regulate gene expression by organizing the genome into active euchromatin regions, where DNA is accessible for transcription, or inactive heterochromatin regions, where DNA is compacted and less accessible for transcription. The aging process causes changes to these regions, which changes gene expression.

The aging process also causes an increase in transcriptional noise, which is the primary cause of variance in the gene expression happening between cells [4]. Researchers compared young and old tissues from several species and identified age-related transcriptional changes in the genes encoding key components of inflammatory, mitochondrial, and lysosomal degradation pathways [5].

 Finally, chromatin remodeling alters chromatin from a condensed state to a transcriptionally accessible state, allowing transcription factors and other DNA binding proteins to access DNA and control gene expression.

Conclusion

If we can find ways to reset age-related epigenetic alterations, we can potentially improve cell function, thus improving tissue and organ health.

One potential approach is the use of reprogramming factors, which reset cells to a developmental state, thus reverting epigenetic changes. We have been doing this for over a decade to create induced pluripotent stem cells, and recent work has seen a therapy based on that technique applied to living animals to reset their epigenetic alterations [6]. This reversed a number of age-related changes, and work is now proceeding with the goal of translating this to humans.

Epigenetic alterations might be considered like a program in a computer, but in this case, it is the cell, not a computer, being given instructions. Ultimately, damage causes changes that contribute to the cell moving from an efficient “program” of youth to a dysfunctional one of old age. If we can reset that program, we can potentially address this hallmark of aging, and a number of researchers are working on that right now.

 

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Maegawa, S., Lu, Y., Tahara, T., Lee, J. T., Madzo, J., Liang, S., … & Issa, J. P. J. (2017). Caloric restriction delays age-related methylation drift. Nature Communications, 8.

[3] Maegawa, S., Hinkal, G., Kim, H. S., Shen, L., Zhang, L., Zhang, J., … & Issa, J. P. J. (2010). Widespread and tissue specific age-related DNA methylation changes in mice. Genome research, 20(3), 332-340.

[4] Bahar, R., Hartmann, C. H., Rodriguez, K. A., Denny, A. D., Busuttil, R. A., Dollé, M. E., … & Vijg, J. (2006). Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature, 441(7096), 1011-1014.

[5] De Magalhães, J. P., Curado, J., & Church, G. M. (2009). Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics, 25(7), 875-881.

[6] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell, 167(7), 1719-1733.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Hallmarks of Aging: Genomic Instability – Article by Steve Hill

Hallmarks of Aging: Genomic Instability – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses one of the hallmarks of aging – in this case, Genomic Instability. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 17, 2017

What is genomic instability?

The cells of your body produce a constant flow of proteins and other materials; these are built according to the blueprints contained in our DNA and are vital to cell function and survival. A large amount of information contained in the DNA is ignored during this process, and this is thought to be junk DNA, remnants of our evolutionary past that are no longer used.

However, if a part of the DNA important to cell function mutates or is damaged, the cell can experience a loss of proteostasis, in which the cell produces misfolded proteins. These misfolded proteins can be very harmful, such as when neurons in the brain produce masses of the toxic amyloid beta protein, as seen in Alzheimer’s disease.

Now, the odd dysfunctional cell is not really a huge problem; however, as we get older, an increasing number of cells succumb to this damage and begin to accumulate in tissue over time. Eventually, the number of these damaged cells reaches a point where tissue or organ function is compromised. Normally, the body removes these problem cells via a self-destruct sequence known as apoptosis, a sort of kill switch that senses the damage and destroys the cell in conjunction with the immune system.

Unfortunately, some cells evade apoptosis, taking up space in the tissue and pumping out inflammatory signals that damage the local tissue. These cells are known as senescent cells, and we will be covering them in a later Hallmarks article.

Another possible outcome of damaged DNA is cells that mutate and do not become senescent cells or destroy themselves via apoptosis. These cells continue to replicate, becoming more mutated each time they divide, and if a mutation damages the systems that regulate cell division or switches off the safety mechanisms against tumor formation, this can lead to cancer. The unchecked and rampant cell growth of cancer is probably the most well-known result of genomic instability.

How DNA damage accumulates

There are many ways for DNA to become damaged. UV rays, radiation, chemicals, and tobacco are all examples of environmental stressors that can damage the genome. Even chemotherapy agents designed to kill cancer can also potentially cause DNA damage and senescent cells, leading to later relapse [2].

Finally, even if we avoided all the external threats to our DNA, the body still damages itself. Reactive oxygen and nitrogen species produced during the operation of normal metabolism can damage both DNA and mitochondrial DNA.

Thankfully, we have evolved a robust network of repair systems and mechanisms that can repair most of this damage. We have enzymes that can detect and repair broken strands of DNA or reverse alterations made to base pairs. This repair process is not perfect, and sometimes the DNA is not repaired. This can lead to the cell replication machinery misreading the information contained in the DNA, causing a mutation.

As mutations are passed to daughter cells, the cell tries to prevent this from happening by checking DNA integrity before and after replication. Unfortunately, some cells do manage to slip through the net.

The consequences of DNA damage

A large number of age-related diseases are linked to damaged DNA or faulty DNA repair systems. Alzheimer’s, Parkinson’s, Lou Gehrig’s disease (ALS), and cancer are all the result of genomic instability.

Another example are the progeric diseases. Progerias are congenital disorders that result in rapid aging-like symptoms and a dramatically shortened lifespan, with Hutchinson-Gilford progeria syndrome (HGPS) probably being the most well known. The disease is caused by a defect in Lamin A, a major component of a protein scaffold on the inner edge of the nucleus called the nuclear lamina. The lamina helps organize nuclear processes, such as RNA and DNA synthesis, and lamins are responsible for supporting key proteins in the DNA repair process.

This defect leads to HGPS sufferers only living until their early 20s and developing atherosclerosis, stiff joints, hair loss and wrinkles, and other accelerated aging-like characteristics.

Conclusion

Despite the various repair systems we have evolved, our body is constantly being assaulted from exposure to environmental stressors and even damaged through its own metabolic processes. Coupled with this, our repair systems also decline in effectiveness over time, meaning that DNA damage and mutations are inevitable.

There is some evidence to suggest that caloric restriction may help combat this, but as of now, no drugs or therapies are available yet that can prevent or repair DNA damage. The good news is human trials for DNA repair are launching this year at Harvard, and Dr. David Sinclair and other researchers are also working on their own solutions.

For the time being, the best we can do is to avoid risks, such as excessive sun exposure, industrial chemicals, smoking, and, of course, staying away from radioactive waste; there are no comic-book superpowers from these mutations!

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Demaria, M., O’Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., … & Alston, S. (2017). Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer discovery, 7(2), 165-176.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Good Sides of Aging? – Article by Nicola Bagalà

The Good Sides of Aging? – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: Nicola Bagalà in this guest article elaborates upon aging as a topic distinguished in terms of Chronological Aging and Biological Aging. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 17, 2017

Sometimes, and especially in articles aimed at mitigating people’s fear of aging, it is said that aging doesn’t come just with downsides, such as frailty and diseases, but also with upsides — for example, wisdom and a long life experience.

It is often subtly implied that these two very different aspects are two sides of the same coin, that you can’t have one without the other, and perhaps even that the ill health of old age is a fair price to pay for the benefits that also come with it.

Nothing could be further from the truth.

Setting the record straight

There are plenty of good reasons to be afraid of aging, because the diseases and disabilities it causes are very real and far from being observed only in exceptional cases. It would be foolish not to fear cancer, for example, because it is an extremely serious and often fatal condition; in the same way, and for the same reasons, it is foolish not to fear aging; perhaps, an even stronger fear is justified, because aging can and does give rise to many diseases, including cancer itself.

There’s nothing wrong with fearing aging, because it may help us steer clear from its inherent dangers, just like the fear of any other harmful thing keeps us away from it. This is true so long as by ‘aging’ we mean biological aging, which is not at all the same as chronological aging. It is very important to draw a line between the two so that we don’t end up accepting the downsides of the former, which are neither necessary nor sufficient to enjoy the benefits of the latter.

What’s the difference?

Chronological aging is a rather fancy term to indicate a very mundane thing, namely the passing of time. For as long as time will keep passing, everything will age chronologically. This is obviously a good thing because if time did not pass, the universe would stand still and nothing at all, including ourselves, would ever happen.

However, it is easy to see how chronological and biological aging are not the same thing by means of a simple observation: Although time runs essentially uniformly everywhere on Earth, different life forms have different health- and lifespans. If time passes at the same rate for me and for a cat, and yet I’m (biologically) old at age 80 while a cat is (biologically) old already at age 15, clearly there must be something else than just the passing of time that accounts for this discrepancy.

This ‘something else’ is metabolism—the intricate set of chemical reactions the bodies of living creatures perform on a daily basis for the very purpose of staying alive. As we have discussed in other articles, what we call biological aging is really just a process of damage accumulation; this damage, which eventually leads to pathologies, is caused by metabolism itself, and therefore a faster metabolism means faster aging. Different species have different metabolic rates; as a rule of thumb, the smaller the species, the faster its metabolism and thus its aging, leading to shorter health- and lifespan. This is, in a nutshell, why a cat ages faster than I do.

As a confirmation of this fact, one may observe that species in a regimen of caloric restriction tend to live longer (sometimes much longer) than their normal lifespan, and the insurgence of age-related diseases is delayed accordingly: A lower caloric intake causes metabolism to slow down; consequently, the aging process follows suit.

Interestingly, some lucky species, the so-called negligibly senescent organisms, don’t show any signs of biological aging at all with the passing of time.

At this point, you don’t have to be clairvoyant to see that biological aging implies chronological aging, but not vice-versa. No chronological aging means no time passing, and no time passing means nothing takes place, metabolism included. However, since different creatures age differently (or not at all) despite time passing at the same rate for all of them, chronological aging doesn’t imply biological aging. Quite simply, they’re not the same thing.

Render unto Caesar the things which are Caesar’s

Having cleared the difference between chronological and biological aging, we must now correctly attribute the aforementioned pros and cons of old age to each of them.

From the very definition of biological aging above, it’s clear that it is the culprit responsible for the cons—the diseases of old age.

Speaking of the pros, all possible benefits of old age—life experience, wisdom, sense of accomplishment—certainly do not come from the damage that metabolism has wrecked throughout your body over the years. Clearly, they depend on the events of your life, and thus they’re not at all granted to happen, no matter how long you live. If you spent your life in isolation doing nothing, avoiding new experiences, and not learning anything new, your wisdom as an eighty-year-old would hardly compare to that of a well-traveled, seasoned scientist or philosopher of the same age, for example. Ultimately, the benefits traditionally attributed to old age obviously depend on the passing of time (i.e., chronological aging), and most of all on the use you made of your time. Just because you’re old, you’re not automatically wise, accomplished, or well-learned.

What’s more, the debilitation that comes with biological aging makes it harder for you to relish and expand the wisdom and experience you’ve accrued over the years. So, not only does biological aging bring no benefits; it is a hindrance as well.

In conclusion, the pros and cons of old age are due to different causes, and, as such, they aren’t interdependent. The diseases of old age are not a currency you can use to buy yourself the wisdom of the aged, and thanks to the emergence of rejuvenation biotechnologies, you might relatively soon be able to enjoy the pros of old age without having to pay any undue and unfair tolls.

 

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age-related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them—which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Jim Mellon Announces Launch of New Book – Juvenescence: Investing in the Age of Longevity – Press Release by Biogerontology Research Foundation

Jim Mellon Announces Launch of New Book – Juvenescence: Investing in the Age of Longevity – Press Release by Biogerontology Research Foundation

Biogerontology Research Foundation


London, UK: Biogerontology Research Foundation Trustee Jim Mellon announces the publication of his newest book, Juvenescence: Investing in the Age of Longevity.

The book is a comprehensive summary of the emerging longevity industry, including profiles of longevity companies, investment opportunities, and aims to chart the major ideas of the geroscience’s thought-leaders and the vast implications this will have on economies and societies.

Often referred to as the British Warren Buffett, Billionaire Jim Mellon is well known for identifying major emerging trends before they become mainstream. Mellon made his wealth by investing in emerging markets throughout the 1990s. After many years of research and investing in the life science sector, Jim announced his vision for the emergence of the nascent longevity industry at Master Investor, one of the UK’s leading investor show in March of 2017, which was attended by over five thousand investors and entrepreneurs.

“The Biogerontology Research Foundation is proud to support what we feel will come to be seen as a landmark publication in the modern history of biogerontology. Jim has put an enormous amount of thought and effort into this new book, and has interviewed many of the field’s leading scientists in his research. The field of geroscience and the emerging longevity industry are both sure to prosper from very well-respected business personalities like Jim Mellon championing the longevity industry and projecting that it will become the world’s largest industry. Further, governments and policy makers should note the pressing need for a paradigm shift in medicine and healthcare away from ‘sick care’ toward comprehensive and disease-preventative healthspan extension. We are proud to have Jim as a Trustee of the Biogerontology Research Foundation and look forward to helping him lend mainstream credibility to the field and actionability to the dawning longevity industry” said Franco Cortese, Deputy Director & Trustee of the Biogerontology Research Foundation.

In 2012, Jim published his best-seller Cracking the Code, which summarized his vision for the future of the life science sector. In 2017, he announced his intention to focus much of his time and assets on the emerging longevity industry and make substantial investments into this area.

Jim and long-time co-author Al Chalabi toured many academic institutions, biopharmaceutical companies, and Silicon Valley tech companies to learn about the latest research and to understand the rapidly advancing field of longevity. Juvenescence highlights the technologies they deem the most likely to generate substantial longevity dividends and create sustainable and profitable industries. They travelled through the US and Europe, interviewing geroscience’s leading scientists and thought-leaders and provide an objective survey of their findings well as a detailed vision for the industry’s future and the most appropriate investment opportunities within the dawning longevity industry.

 

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Earlier this year Jim Mellon announced the formation of Juvenescence Limited, a company investing in the longevity biotechnology. Since then the company announced investments in several high-profile longevity companies including Insilico Medicine, Inc, a Baltimore-based leader in artificial intelligence for drug discovery, biomarker development, and aging research.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

Our Moral Obligation to Cure Aging – Aubrey de Grey Interviewed by Why? Radio

Our Moral Obligation to Cure Aging – Aubrey de Grey Interviewed by Why? Radio

Dr. Aubrey de Grey

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Dr. Aubrey de Grey in this interview explains and advocates for curing of aging, i.e., rejuvenation of the old to become youthful; preventing the youth from being old biologically, and other related points.

Aubrey de Grey is the U.S. Transhumanist Party’s Anti-Aging Advisor. He is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging.

This interview was conducted by Why? Radio, a program of the Institute for Philosophy in Public Life. You can also find it here.

 

 

 

Biogerontology Research Foundation Launches Campaign for Photographic Biomarkers of Age

Biogerontology Research Foundation Launches Campaign for Photographic Biomarkers of Age

Biogerontology Research Foundation


Thursday, August 31st, 2017, London, UK: The Biogerontology Research Foundation announces the launch of a crowdfunding campaign, MouseAge, to develop and test photographic biomarkers of ageing in mice in collaboration with scientists from Harvard University, University of Oxford, Youth Laboratories and Insilico Medicine. The project’s aim is to develop novel biomarkers of ageing in mice for the purposes of testing the effect of healthspan and lifespan-extending interventions. The project is now live at Lifespan.io, a crowdfunding platform for ageing research institutions that has launched several successful campaigns for SENS Research Foundation, International Longevity Alliance and CellAge.

“One of the most fundamental challenges in ageing research today is the development of robust and reliable biomarkers of ageing to serve as the basis by which the efficacy of lifespan and healthspan-extending interventions can be tested. Humans live a long time, and testing the effect of geroprotective interventions in humans using lifespan gains as the main criterion for success would be wildly impractical, necessitating long and costly longitudinal studies. By developing accurate biomarkers of ageing, the efficacy of potential geroprotective interventions could instead be tested according to changes in study participants’ biomarkers of ageing. While significant attention is paid to the development of highly accurate biomarkers of ageing, less attention is paid to developing actionable biomarkers of ageing that can be tested inexpensively using the tools at hand to the majority of researchers and clinicians. The Biogerontology Research Foundation chose to support MouseAge.org because photographic biomarkers of ageing represents a highly actionable alternative to more expensive measures of biological age.” said Franco Cortese, Deputy Director & Trustee of the Biogerongology Research Foundation.

The project utilizes Insilico Medicine’s novel deep learning platforms to correlate changes in physical appearance with biological and chronological age. Insilico is leading the pack in the intersection of deep learning and ageing research, and is well known for its use of advances in genomics, big data analysis, and deep learning for in silico drug discovery and drug repurposing for ageing and age-related diseases. The Biogerontology Research Foundation has collaborated with Insilico Medicine in the development of actionable and practical biomarkers of ageing before through their Ageing.AI project, and both organizations hope that MouseAge is the next in a long line of continuing research into the development of actionable biomarkers of ageing via the intersection of longevity research and deep learning.

“There are many experiments conducted around the world that examine lifespan in mice. The artificially intelligent MouseAge system will help determine which interventions make mice look younger. The plan is to develop an accurate predictor of mouse biological age based on images of mice and then apply transfer learning techniques to other datasets and data types,” said Vadim Gladyshev, MouseAge Research Lead and Professor of Medicine at Brigham and Women’s Hospital, Harvard Medical School.

Milestones for the project include the design of standardized protocols for creating photos and videos of mice, developing a mobile app and server infrastructure for image data collection, developing and testing the project’s main algorithm for mouse age prediction, optimizing feature extraction to investigate visual biomarkers of ageing in mice, creating a central data repository for the project’s data, utilizing transfer learning techniques to make these methods applicable to other model organisms, and ultimately using transfer learning techniques to develop photographic biomarkers of ageing in humans. The project’s principal investigator is Anastasia Georgievskaya, co-founder of Youth Laboratories, a company working at the intersection of ageing research, AI and machine vision, with the ultimate goal of using facial imageing data to predict patient health status.

The ultimate end-goal of MouseAge is to develop an intuitive mobile app to be used by researchers across the globe free of charge, where users can take images of model organisms and have the project’s DP-based algorithms perform age-assessment of images uploaded by users of the app. Both the organizations and researchers behind MouseAge are united in their belief in the promise of AI to accelerate ageing research and to streamline the development of effective healthspan-extending interventions for use in human patients, and hope that MouseAge comes to be remembered as an important landmark in the ongoing paradigm shift away from costly and inefficient sick-care and toward morbidity compression and effective healthspan extension for the benefit of all.

“Ageing research is the most altruistic cause that can generate billions of quality-adjusted life years over time and save the global economy. We are very happy to contribute to and support the MouseAge project. Our Young.AI system for tracking multiple biomarkers during human ageing is currently in the alpha stage and is launching in the fall. However, the biological relevance of many of the biomarkers and interventions is yet to be established, and the MouseAge project contributes to the body of fundamental science required to bridge AI and longevity research. Please support the MouseAge project on LifeSpan.io to contribute to this grand effort”, said Alex Zhavoronkov, PhD, Chief Science Officer of the Biogerontology Research Foundation.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

MouseAge: Using Artificial Intelligence to Determine Age and Assess Therapies Against Aging – Project by Lifespan.io

MouseAge: Using Artificial Intelligence to Determine Age and Assess Therapies Against Aging – Project by Lifespan.io

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United States Transhumanist Party


According to Article 3, Section V of the Constitution of the United States Transhumanist Party:

“The United States Transhumanist Party supports concerted research in effort to eradicate disease and illness that wreak havoc upon and cause death of sapient beings. We strongly advocate the increase and redirection of research funds to conduct research and experiments and to explore life, science, technology, medicine, and extraterrestrial realms to improve all sentient entities.”

Which is why the U.S. Transhumanist Party is pleased to announce the official launch of the fundraising campaign for the MouseAge project. MouseAge is a longevity-based project started by one of our Allied Organizations, Lifespan.io, of which we’ll provide relevant information below:

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Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

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Biogerontology Research Foundation


Scientists at the Biogerontology Research FoundationFeinberg School of Medicine at Northwestern University and Swammerdam Institute of Life Sciences at the University of Amsterdam have published a paper on a proposed method of in situ tissue regeneration called Induced Cell Turnover (ICT) in the journal Human Gene Therapy. The proposed therapeutic modality would aim to coordinate the targeted ablation of endogenous cells with the administration of minimally-differentiated, hPSC-derived cells in a gradual and multi-phasic manner so as to extrinsically mediate the turnover and replacement of whole tissues and organs with stem-cell derived cells.

“One of the major hurdles limiting traditional cell therapies is low levels of engraftment and retention, which is caused in part by cells only being able to engraft at locations of existing cell loss, and by the fact that many of those vacancies have already become occupied by ECM and fibroblasts (i.e. scar tissue) by the time the cells are administered, long after the actual occurrence of cell loss. The crux underlying ICT is to coordinate endogenous cell ablation (i.e. induced apoptosis) with replacement cell administration so as to manually vacate niches for new cells to engraft, coordinating these two events in space and time so as to minimize the ability for sites of cell loss to become occupied by ECM and fibroblasts. This would be done in a gradual and multi-phasic manner so as to avoid acute tissue failure resulting from the transient absence of too many cells at any one time. While the notion of endogenous cell clearance prior to replacement cell administration has become routine for bone marrow transplants, it isn’t really on the horizon of researchers and clinicians working with solid tissues, and this is something we’d like to change,” said Franco Cortese, Deputy Director and Trustee of the Biogerontology Research Foundation, and lead author on the paper.

Cell-type and tissue-specific rates of induced turnover could be achieved using cell-type specific pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic AAV-delivered suicide genes driven by cell-type specific promoters. Because these sites of ablation would still be “fresh” when replacement cells are administered, the presumption is that the patterns of ablation will make administered cells more likely to engraft where they should, in freshly vacated niches where the signals promoting cell migration and engraftment are still active. By varying the dose of cell-type targeted ablative agents, cell type and tissue-specific rates of induced turnover could be achieved, allowing for the rate and spatial distribution of turnover to be tuned to the size of the tissue in order to avoid ablating too many cells at once and inadvertently inducing acute tissue failure.

“Cell therapies are limited by low levels of engraftment, and in principle their ability to improve clinical outcomes is limited by the fact that they can only engraft at locations of existing cell loss. Conversely, therapeutic tissue and organ engineering requires surgery, is more likely to introduce biochemical and mechanical abnormalities to tissue ultrastructure through the decellularization process, and is fundamentally incapable of replacing distributed tissues and structures with a high degree of interconnectivity to other tissues in the body. The aim of ICT is to form a bridge between these two main pillars of regenerative medicine, extending the efficacy of cell therapies beyond a patch for existing cell loss and accomplishing the aim of tissue and organ engineering (i.e. the replacement and regeneration of whole tissues and organs) while potentially remaining free of some of their present limitations,” said Giovanni Santostasi, co-author on the paper and a researcher at the Feinberg School of Medicine, Northwestern University.

While future iterations of the therapy could use patient-derived cells, such as ESCs derived via somatic cell nuclear transfer (SCNT) or iPSCs derived from nuclear reprogramming, shorter-term applications would likely use existing stem cell lines immunologically matched to the patient via HLA matching. The authors contend that the cloning of adult organisms with normal lifespans from adult somatic cells testifies to the fact that adult cells can be rejuvenated and used to produce a sufficient quantity of daughter cells to replace the sum of cells constituting adult organisms, and that serial cloning experiments (in which this process is done iteratively, using an adult cell of each subsequent generation to derive the next) attests to this fact even more strongly.

“ICT could theoretically enable the controlled turnover and rejuvenation of aged tissues. The technique is particularly applicable to tissues that are not amenable to growth ex vivo and implantation (as with solid organs) – such as the vascular, lymphatic, and nervous systems. The method relies upon targeted ablation of old, damaged and/or senescent cells, coupled with a titrated replacement with patient-derived semi-differentiated stem and progenitor cells. By gradually replacing the old cells with new cells, entire tissues can be replaced in situ. The body naturally turns over tissues, but not all tissues and perhaps not optimally. I am reminded of the quote attributed to Heraclitus: ‘No man ever steps in the same river twice, for it’s not the same river and he’s not the same man,'” said Sebastian Aguiar, a coauthor on the paper and researcher at the Swammerdam Institute of Life Sciences, University of Amsterdam.

“Reversing aging in humans will require a multi-step approach at multiple levels of the organismal organization. In situ targeted ablation of the senescent cells and regeneration will be an important component of comprehensive anti-aging therapies,” said Alex Zhavoronkov, Chief Science Officer of the Biogerontology Research Foundation.

The researchers originally proposed ICT in 2016 in the context of biomedical gerontology as a possible means of preventing and/or negating age-related phenotypic deviation for the purposes of healthspan extension, and in this new paper they refine the methodological underpinnings of the approach, take a closer look at potential complications and strategies for their deterrence, and analyze ICT in the context of regenerative medicine as an intervention for a broader range of conditions based on disease or dysfunction at the cellular and intercellular level, with potential utilities absent from traditional cell therapies and tissue/organ engineering, the two main pillars of regenerative medicine. The intervention is still very much conceptual, and any potential utilities over other therapeutic modalities within regenerative medicine would need to be verified via preclinical studies, but their hope is to stimulate further research at this interface between geroscience and regenerative medicine.

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The paper is available here.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

LEAF Interview with Dr. Aubrey de Grey: Controlling the Main Aging Damages

LEAF Interview with Dr. Aubrey de Grey: Controlling the Main Aging Damages

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Aubrey de Grey and Life Extension Advocacy Foundation


The U.S. Transhumanist Party is pleased to feature this interview of Dr. Aubrey de Grey, the Transhumanist Party’s Anti-Aging Advisor, conducted by Elena Milova of the Life Extension Advocacy Foundation (LEAF), one of the Transhumanist Party’s most active Allied Organizations. You can also see this interview on YouTube here.

Description by LEAF: Please enjoy this interview with Dr. Aubrey de Grey, Chief Science Officer and Co-founder of SENS Research Foundation — one of the most successful advocacy and fundraising initiatives supporting breakthrough research on the main mechanisms of aging and age-related diseases.

In this video Dr. de Grey speaks about the progress in developing interventions to tackle age-related damages identified by SENS as the main ones.

Interviewer – LEAF/Lifespan.io Board member Elena Milova.

Dr. de Grey received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. He is Editor-in-Chief of Rejuvenation Research , is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organizations.

Subscribe to Lifespan.io’s YouTube channel for more.

This interview is presented by LEAF. Please support its work by becoming a “Lifespan Hero“.

Why I Fear Aging – Article by Hayley Harrison

Why I Fear Aging – Article by Hayley Harrison

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Hayley Harrison


My mother had leukemia. I really loved her, and she really loved me. When I went to the supermarket at night, she asked me to hurry back, and said she was worried about me. She really enjoyed my company and talking to me. She could talk to me about things she couldn’t tell anyone else. It was like we were best friends. Even though my mom was 74 when she died. I was adopted when my mom was 51 and my dad was 57, so they were already older.

I was closer to her than to any member of my family. Since I lost her, I feel like I’ve lost everything. Aging made her really sick. I found out that the AML leukemia that my mom had mostly affects the elderly.

My father has been in hospital nearly two weeks. He had an operation to remove something on his lung. He’s been unwell for a few weeks now. His appetite has gone right down. He kept sleeping in the chair a lot because of the infection. He’s 81. He’s had tests to see if he has cancer, but we don’t know the results yet.

My friend told me that if my father hadn’t have had the biopsy, his chest infection would have turned into pneumonia, and that would have killed him. The antibiotics have not worked yet. So I keep thinking, “What’s going to happen to him?”. I love my father, too.

If anti-aging medicine were available now, the doctors could have treated my mother as well as my father. My mother’s leukemia was caused by aging, as I discovered. I’d love to be able to talk with my mother and father again.

I don’t want to get old, because I don’t want to get decrepit and sick. The thought of me being so shrivelled up like my parents have got terrifies me.

This is why I’m so motivated to cure aging. I’m trying to do everything I can. I keep hearing a lot that science to cure aging is underfunded. I share science articles and promote science. I’m writing this article to get the message out to all the people about getting aging under medical control.

There’s quite a few people trying to solve the aging problem. Aubrey de Grey and SENS are working on rejuvenation biotechnology. They are doing this by solving the seven deadly causes of aging. These include cell loss, junk inside and outside the cell, extracellular crosslinks, death-resistant cells, and cancerous cells.

Imagine a world where nobody gets old anymore, where everyone is young and healthy. Some people would like to do their favorite sports again, and currently they cannot because of aging.

If I lived forever, I would look to have more confidence. I would try to not be scared of people anymore.

If I were to live longer, I’d imagine I could hang out with a few of my friends in America. I enjoy fashion. I have always wanted to look like a model. I would have the time to select the best clothing and look fantastic.

Hayley Harrison is an Allied Member of the United States Transhumanist Party and the Nevada Transhumanist Party. She resides in the United Kingdom.