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 .
~ 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 . 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 . 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 . 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 .
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 . 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.
 López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
 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.
 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.
 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.
 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.
Gennady Stolyarov II
Gennady Stolyarov II, Chairman of the United States Transhumanist Party, discusses why longevity research is crucial, and how our generation stands on the threshold of finally dealing a decisive blow to the age-old enemies of aging and death, which have destroyed great human minds since the emergence of our species.
This video is part of the #IAmTheLifespan campaign, coordinated by Lifespan.io and the Life Extension Advocacy Foundation (LEAF) for Longevity Month, October 2017. Read more about this campaign here.
Become a member of the U.S. Transhumanist Party for free, no matter where you reside. Fill out our Membership Application Form here.
Become a Foreign Ambassador for the U.S. Transhumanist Party. Apply here.
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:
Elena Milova and Keith Comito
The U.S. Transhumanist Party is pleased to share this infographic from our friends at the Life Extension Advocacy Foundation (LEAF), one of the Transhumanist Party’s most active Allied Organizations. Life-extension advocates Elena Milova and Keith Comito have compiled a set of tips for communicating ideas regarding the progress of medical science and technology, for the pursuit of healthy life extension, in such a manner as to enable many in the general public to understand and sympathize with our goals and the science behind them. We encourage you to distribute this infographic to any activists and advocates who you think would benefit from the advice therein.
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“.
Lifespan.io and CellAge
The Transhumanist Party supports Lifespan.io and CellAge in their work towards groundbreaking scientific life-extension research. Finding a way to repair age-related damage to senescent cells would be a fundamental breakthrough for transhumanism, and we offer our best wishes and support for those striving towards these new technologies.
Here is an update from Lifespan.io and CellAge:
If you haven’t already noticed, our latest Campaign, CellAge, has been having a bit of difficulty in reaching its funding goal. So, in order to solve that problem, we asked all our backers from previous campaigns for feedback on how we can improve the current CellAge campaign.
We’ve gotten a staggering number of responses (which we’re still personally replying to) and have compiled all the reasons into one big, dramatic “what could have gone better” spreadsheet.
One of those reasons was that CellAge did not have a fund match.
CellAge is now endorsed by LongeCity. And they’re running a Fund Match up to $3000.
For those who don’t know, LongeCity is one of the oldest, most respected international pro-longevity organizations. Their exclusive forum boasts thousands of individuals learning, discussing and sharing latest breakthroughs of anything that has to do with slowing down aging.
Apart from generously contributing $800 right away, LongeCity is also running an internal fund match: anything donated via this special page before the 18th of February, will be doubled up to $3000.
To have them support CellAge means that they understand the significance of its success.
What makes this even more exciting is that CellAge has managed to secure additional external funding for their project, which means that they will be able to achieve the same goals even sooner.
The initial goal will now be $20,000, with all stretch goals being reduced as well.
Having raised over $15,000 so far, along with the fund match, means we’re incredibly close to successfully funding CellAge’s exciting research.
Just a quick refresher: CellAge is using customised synthetic biology to develop cutting edge ways to detect and destroy senescent cells, which contribute to age-related diseases. By developing this technology we will be able to give researchers a superior tool for finding senescent cells, and improving the quality of stem cell therapies.
Ultimately this will lead to a better way to remove problem senescent cells without the side effects traditional small molecules inevitably cause. In short, this technology can help start a revolution in medical research and a leap in how we treat age-related diseases for a healthier future.
If you’re still undecided, remember, every dollar you put into the LongeCity match will become two for CellAge.
-The Lifespan Team