https://www.lifespan.io/ending-age-related-diseases-2023/

 

The good folks from Lifespan.io have asked whether LongeCity would sponsor this event as we have in the past. 

 

The sponsorship would come with a free ticket, but unfortunately, Mind has reported from other conferences cannot attend. 

 

Is there another LongeCity member whom would like to go?

 

- You need to be a member (but if this entices you to join for the first time, that's fine) 

- You promise to write a conference report and share it on this forum 

- If we manage to send you some LC flyers, you promise to hand them out (or at least put them somewhere where people can take them)

 

If you are interested, please use the contact form ("small grants" tab) ASAP 

 

 

View attachment: leafcon.png

We are now looking for early stage contributors and testers for a new community biomarker database LongeCity is developing with OpenCures.

→ https://www.longecity.org/BASE/

We are researching the biomarkers in breath and planning a small pilot study with a handful of volunteers in the San Francisco Bay area.

The attached leaflet explains the background and procedure.
Giving a breath sample (at the SENS Foundation parking lot, in Mountain View) takes five minutes.
Sampling appointments can be booked for any timeslot (including evening and weekends) 01-14th March by emailing: alexandra.stolzing@sens.org

We need volunteers across a wide age range, so please state your age when you make contact and don't be disappointed that we cannot accept everyone.
If there are any questions please feel free to contact: Prof. Alexandra Stolzing at the address above
And please feel free to share this invite with those interested in aging research, especially seniors.

participant information leaflet (.pdf)
link to video about the breath sampler

On May 7, a study was posted on bioRxiv that has all the apprearance of a potential major breakthrough in anti-aging research. The researchers claim they've made a mammal 54% younger with a few simple injections. The internet has been buzzing about the news ever since, with Josh Mitteldorf, who has written two books on aging, writing, "I believe major rejuvenation has been achieved in a mammal, using a relatively benign intervention that shows promise of scaling up to humans. I'm going to stake my reputation on it."
The paper describes treating old rats with injections derived from the blood plasma of young rats. As a result, the old rats showed DNA methylation clocks more typical of younger rats.
bioRxiv is a site for publishing pre-print scientific papers, that is to say, ones that have not finished the process of peer-review. The authors aim to publish the paper in a peer-reviewed journal. In its current form, the paper is missing important data and the experiment cannot be reproduced.
Methylation patterns were rolled back 75% in liver tissue, 66% in blood, 57% in heart tissue, and 19% in the hypothalamus: an average rejuvenation of 54.2% across four tissues. It is notable that not all tissues showed equal improvement on the methylation clock. In particular, the hypothalamus seemed stubborn. However, the treated rats "learned and remembered better" than the controls. Strength was up, fat was down, good cholesterol up, bad cholesterol down, and the biomarkers measured in the blood "were altered towards the values of young rats, without exception."
David Sinclair, a tenured professor at Harvard genetics department and a regular in the media, commented favourably on the paper, saying, "So are the result believable? I see nothing wrong with the epigenetic clock analyses, the stats "Horvath is the best there is. It's also hard to see how the other measures could be messed up."
So far it sounds like we should get pretty excited. Let's take a look at what the theoretical basis of the research, the empirical results, and the pathway from here to human rejuvenation. 

Methylation theory
The researcher, Harold Katcher, made his name as co-discoverer of the breast cancer gene, brca1, in 1994 and has published actively since then. He writes, "I have thousands of citations in the literature, with publications ranging from the discovery of the human 'breast cancer gene', to protein structure, bacteriology, biotechnology, bioinformatics, and biochemistry". 
Another co-author is Steve Horvath, the developer of 'Horvath's clock', a way of measuring the biological age of tissues based on which genes are active, versus which genes have methyl locks on them.
The team and their research represents a mild rebellion in the ranks of aging research. The dominant theory about biological aging  --but not the only respectable one -- is about damage. The body, in its day-to-day running, accumulates damage, much like wear on machine parts. Over time the damage builds up, causing what we know as old age.
Katcher (along with Tom Rando, Michael and Irina Conboy, and others) believe something different. Molecules in the blood give instructions to cells telling them to act young or old, and part of what it means to 'act old' is to lock down some repair mechanisms. They believe that the body has mechanisms capable of repairing the damage, but doesn't use them. 
Gene expression can be locked down by modifications called 'methylation'. For example, in response to fasting, certain genes that control appetite become methylated and switch off. According to the methylation theory of aging, our body's repair mechanisms become methylated over time, leading to the breakdown and age-related diseases.
There is some good evidence backing the methylation theory. By measuring the methylation of DNA, scientists can tell the age of a tissue sample to within 5% accuracy. Factors known to accelerate aging -such as obesity and Down's syndrome-  also accelerate DNA methylation. Katcher presented the argument in a 2013 essay called 'Studies that Shed New Light on Aging', and also in a 2015 paper 'Towards an evidence based theory of aging'.
It would be good news if the methylation theory is true. Repairing cellular damage would be hard, but if cells can be old or young depending on what signals they receive, then we need only identify the signalling molecules and inject them. The race is on. Two years ago, with funding from Akshay Sanghavi, Katcher set up a lab in Mumbai and got busy turning the methylation theory of aging into a practical therapy.

The mysterious 'Elixir'
The current study used six young rats (aged 30 weeks), and 12 old rats (aged 109 weeks), half of whom got the treatment and half of whom did not. The old rats in the treatment group were injected with something derived from the blood plasma of the young rats. What exactly? The paper is thin on details, just calling it "plasma fraction". Until Katcher and his partner Akshay Sanghavi can get a patent, they are keeping the recipe a secret. Katcher has repeatedly stated that he expects the relevant molecules can be synthesised without the need to harvest blood from young people. 
The desire to protect their discovery is understandable, but one could argue that they should have held off on publishing the experiment until their patents were secured. Reproducibility is a key part of the scientific method, and it is impossible to reproduce their study as it stands. (As a side note, the instrument used in DNA methylation profiling also falls short of reproducibility. The paper describes it as a "custom array contains two thousand probes selected from human biomarker studies" without specifying what these probes are.)
The treatment described in the paper is agreeably non-invasive: "Plasma fraction treatment consists of two series of IV injections, four times on alternate days for 8 days. A 2nd series of injections were given 95 days later. In its entirety, the experiment lasted 155 days." Katcher has said that if this becomes a human therapy, it would require a series of injections every few years.
Katcher's initial plan had been to give old rats the whole blood plasma of young rats. But in the current paper, blood plasma per se was not used, but an unknown 'something' from the plasma. The paper says "Although transfusion technologies for humans are well-developed and safe, transfusion of small animals is still at the infancy stage of development, requiring state-of-the-art techniques and remains challenging. We used a unique plasma fraction "Elixir" developed by Nugenics Research." (Nugenics is Sanghavi and Katcher's company.)
David Sinclair comments, "What is in the plasma fraction that helps? Proteins, small chemicals, exosomes?" We don't know, but Katcher's statements that the substance can be synthesised makes exosomes unlikely.

Measuring rejuvenation
Whatever it is, it seems to have worked. The paper reports, "Crucially, plasma treatment of the old rats [109 weeks] reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats [30 weeks]... According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%. In other words, the treatment more than halved the epigenetic age."
The study required a new clock to quantify the age of rats from their DNA methylation. The paper says, "To build the human-rat clock, we analyzed previously generated methylation data from n=850 human tissue samples". It seems unusual to use human tissue as a source of data for studying rat tissues. The paper does not explain why human tissue was used. What's even stranger is that the human tissue samples are from AIDS patients, from the Cape Town Adolescent Antiretroviral Cohort study, and the National NeuroAIDS Tissue Consortium which "collects and distributes well-characterized antemortem and postmortem tissue specimens with clinical and serological data from HIV-infected individuals". Why was methylation data from HIV-infected humans used to train a rat model? Did they only take data from the non-HIV-infected controls? The paper doesn't say. It is likely that using AIDS sufferers rather than healthy people could distort the DNA methylation data.
It wouldn't be that interesting if a fringe group developed a clock not generally thought to be important to aging, and then reset that clock. But that's not the only change measured in the rats. The paper also reports changes in senescence burden, biomarker levels, and behaviour.

Senescent cells
"Plasma fraction treatment reduced the level of senescent cells by a very considerable degree". David Sinclair comments, "senescent cells were reduced "by a very considerable degree". Presumably, the immune system cleared the senescent cells. This is what the field is looking for." Part of what makes this interesting is that senescent cell burden is separate from epigenetic aging; if a treatment directly addresses aging in the methylation paradigm, and somehow leads to senescent cells also being cleared up, that indicates a broad-spectrum rejuvenation. However, the quality of the data on senescent cells is low: the effect is shown by images, with the accompanying statistical analysis notably absent. It is unusual, even for a pre-print awaiting peer review, to be missing this data. Someone familiar with the technique of staining to detect senescence markers notes that there seems to be an unusual amount of blue staining in the brain tissue of the old rat, possibly indicating a methodological error. (Fig 7 of the paper, click for image) 

Outside of the group of scientists who believe that DNA methylation is key to aging, others believe that senescent cells and inflammation are to blame. Katcher's work shows promising results at addressing these problems. The paper says, "Plasma fraction treatment reduced the level of senescent cells by a very considerable degree", and Katcher has commented, "I can definitively say that chronic inflammation due to aging can be reversed with factors present in young blood". As senescent cells and inflammation markers weren't specifically removed by the intervention, it seems to work by flipping epigenetic switches, turning on the body's disposal mechanisms to clear out the trash.

Biomarker results
The paper claims that "accumulation of fat in old tissues was greatly reduced". However, no quantified measures of adipose tissue accompany this claim, as would be expected in the scientific community.
Biomarkers in the old rats "were altered towards the values of young rats, without exception". Biomarkers tested include total bilirubin, direct bilirubin, SPGT (serum  glutamic-pyruvic  transaminase), SGOT (serum glutamic-oxaloacetic transaminase), triglyceride, HDL (high-density lipoprotein), cholesterol, glucose, creatinine, BUN (blood  urea  nitrogen), total protein, IL-6 (a marker of inflammation), and oxidation markers glutathione (GSH) and superoxide dismutase (SOD). Again, the data here leaves something to be desired: it is presented as graphs without detailed numbers or statistical analysis.

Behavioural results
Performance in cognitive tests improved: "it was clear that treated rats remembered the maze much better than the untreated ones". Strength also increased. They write that "At 15 days post-treatment, the strength of plasma fraction-treated old rats was indistinguishable from that of young ones." However, it seems behaviour was not measured under conditions of blinding.

Conclusion
Regardless of what was in the plasma fraction, and regardless of whether this ever scales up to humans, the study is noteworthy for major rejuvenation in a mammal. (Tiny creatures like yeast and nematodes have been rejuvenated before.) It seems likely that the same results could be achieved by taking the blood plasma from a young animal and putting it into an old animal. Early rumours of Katcher's research suggested this. A study published in 'Nature' in 2014, and another in 2016 also lend weight to the rejuvenating powers of young blood.
It's not easy to transfuse plasma in small animals like rats. Blood loss becomes an issue. Mechanically it's easier in humans, but what about morally? The fear of Countess Bathory scenarios where the rich and old need the blood of the young and poor is at the forefront of much popular writing around this area, and dominated the Reddit comments on the research. If Katcher's team have identified and isolated molecules in young plasma that can have the same effect, that is a significant breakthrough that will shape the field in years to come.
Improved physical and cognitive performance are nice, but what would really convince the skeptics is data on how long these rats live. If treated mice lived two years longer than controls, the team will have a promising treatment on their hands. There's no way to get that data but to wait, and restrictions caused by the Covid-19 pandemic are delaying research.
Katcher and Sanghvi have not yet found a suitable partner to provide financing for human trials, and have not yet applied for patents, with Sanghvi commenting, "we plan to file patents worldwide sometime this year". Until the patents are filed, the nature of the treatment will remain a secret. Human trials may also take years to get approved and conducted. In the meantime, none of us are getting any younger.

Initial fundraiser text below
further updates and comments in the corresponding forum thread

For years while Victor pursued his studies he has been active in organizations promoting research and activism for longer and healthier lifespans -- including many contributions to the LongeCity community. After obtaining his degree Victor, originally from Sweden, was thrilled to be recruited to intern at an aging research company in the San Francisco Bay Area. Now, because of COVID19, his engagement had to be terminated and Victor’s visa is in peril.

With the goodwill of supporters, we hope to raise enough funds to enable Victor to stay and work with one of our Affiliate Labs in the area:

OpenCures, the latest venture by our former Director Kevin Perrott helps self-directed researchers access cutting-edge tools such as mass spectrometry to self-evaluate their biomarkers. Classified as an essential biotech, OpenCures is not restricted by the current lockdown provisions. 
At OpenCures, Victor could not only gain valuable experience and training but also help with a key project for LongeCity:
 
Biomarkers of Aging Self Experimentation (BASE) aims to advance longevity science by collating data from scientific sources and personal test results in a curated community format.
The project will empower LongeCity members to analyse and understand their own data, recruit new ‘citizen scientists’ to the community, and provide a valuable open source reference for researchers. 

OpenCures -with Victors input- are the ideal partner for this community initiative.

Fundraiser Goal: $13 000.- 
- LongeCity will MATCH each donation -- for a total of $26K! 

This fundraiser will cover the minimum expenses for Victor’s lawful employment at OpenCures for the remainder of his visa and the technical and conceptual development of the BASE project. Funds will be collected by LongeCity and transferred to OpenCures as a research grant. 

Donations can be made ⇒ here via paypal or credit card.
You do not need a paypal account - but select 'paypal' as payment processor for credit card payments. You also do not have to register or join (but if you are a Member remember to log in first so the donation can be duly credited to you). 
We will gladly issue you with a receipt for tax purposes upon request. You can track the progress from the ⇒forum index page. 


LongeCity (Longecity.org/ImmInst.org) is an international, not-for-profit, membership-based organization (⇒more info) LongeCity’s approach to supporting regenerative science has always been characterized by small-scale, high-impact projects sourced and steered by and in connection with its community. Years before ‘crowdfunding’ and ‘citizen science’ became well known concepts they were practiced at LongeCity. You can read about some of our previous initiatives ⇒here & here 

For any questions please contact info@longecity.org.

SPONSORRED GUEST ARTICLE

Eternus Science

Neurohacker Collective put rigorous research into the formulation of their Qualia nootropic stack products which debuted in 2016. They now have turned their research to the riddle of aging and the decreased cellular energy that initiates many aging symptoms. The result is Eternus, a 36 ingredient formula designed to be the most comprehensive stack on the market for cell energy support, and delaying the effects of aging as long as possible.
Aging begins at the cellular level. The roughly 37 trillion cells in our bodies are performing trillions of metabolic functions each second. Decreases to the efficiency and energy of cellular function, underlies virtually all symptoms we associate with aging, from wrinkling skin and sagging muscles, to greater lethargy and brain fog, to poorer sleep and longer physical recovery times.
Comprehensive support for cell energy and efficiency lies at the bedrock of limiting the effects of the aging process, but it is an incredibly complex challenge. We all age, but the rate of aging and the negative symptoms associated with that process are highly variable. To make the rate and symptoms of aging as slow and subtle as possible, a nutritional formula must account for a broad range of cellular functions simultaneously.
These types of complex formulation requirements are where Neurohacker Collective separate themselves from most stack formulators. They specialize in formulation modeling premised on complex systems science, which incorporates dozens of ingredients dosed in precise synergistic relationships with each other, to support the body’s biochemical pathways to self regulate optimally. This approach is in contrast to a lot of pharma and nutra formulators who override those pathways to achieve an isolated benefit by externalizing side effects to other parts of the body, which can further exacerbate regulatory dysfunction.
The following is a deep dive into Eternus, which addresses cell energy and the aging process in at least 6 distinctive ways.

What is Eternus?

Eternus is a natural cell energy stack designed to comprehensively limit the negative effects of the aging process. It has been formulated by Neurohacker Collective, a San Diego-based company with a mission to create products that improve human performance by supporting our natural complex physiology rather than overriding it.

6 Ways Eternus Supports Cell Energy & Better Aging

1) Promotes a Fitter Mitochondrial Network

If your mitochondria don’t function properly, your cells will struggle to produce energy. With insufficient energy being produced, you’ll feel more tired and lethargic (R).
And poor mitochondrial health doesn’t only cause physical sluggishness.It also is linked to brain fog and neurodegenerative diseases, while improving mitochondrial function may reverse these conditions (R, R, R).
The mitochondria also initiate the production of steroid hormones, including cortisol and all sex hormones. That’s why malfunctioning mitochondria can cause hormone imbalances (R).
Another key function of the mitochondria is to commit cellular suicide – known as apoptosis – in response to excess stress, damage, or mutations. Evolutionarily, it is better for the damaged cells to commit suicide than to spread more oxidative stress, or to go on and damage other cells which can potentially develop into cancers (R).
Supporting the mitochondria and reducing oxidative stress generally protects the neurons by preventing apoptosis. In a small clinical study, a comprehensive natural approach (supplements, diet, lifestyle) sustainably reversed cognitive decline in 10 elderly patients. The program focused on reducing brain inflammation, and supporting the mitochondria and brain plasticity (R).
Eternus has a multitude of ingredients with research correlating to various aspects of improved mitochondrial health and function, including resveratrol (R), lipoic acid (R), n-acetyl-L-cysteine (R), and Coq10 (R).

2) Boosts Production of NAD+ & Optimizes NAD+: NADH Ratio

Nicotinamide adenine dinucleotide (NAD) is a coenzyme that consists of adenine and nicotinamide, and is found in all living cells.
NAD exists in two forms: NAD+ and NADH respectively. NADH contains 2 more electrons than NAD+.
Low NAD+ quickens aging. In mitochondria of young people, NADH can readily donate its electrons to generate NAD+. During the aging process, increased DNA damage reduces NAD+, leading to reduced SIRT1 activity and reduced mitochondrial function (R ).
In addition, during aging, the decline in the function of genes that control circadian rhythm can reduce NAD+ levels (R).
NAD+ also has compelling correlations to cognitive health. In a mouse model of Alzheimer’s disease, increasing NAD+ by supplementing with nicotinamide riboside restores cognitive function by increasing PGC-1alpha levels (R).
Supplementation with NAD+ intermediates, readily increases cellular and mitochondrial NAD+, and reverse many aging or disease processes associated with low NAD+ (R, R2). There is strong evidence that B vitamin levels have direct correlations to NAD+ production (R), with niacinamide (B3) in particular showing a particularly strong correlation (R). Eternus supplies a stack of B1, B2, B3, B5, B7, B9 and B12 vitamins in its formula.
While boosting NAD+ is a useful strategy, it’s also important to increase the NAD+ : NADH ratio. Increasing the cellular consumption of NADH is an additional lever toward that end. Calorie restriction induces an enzyme called Nrf2, which is considered to be a master regulator of cellular defense; it’s responsible for many cellular protection processes and involved in mitochondrial biogenesis (i.e., building new mitochondria). This enzyme then changes how other genes (and the enzymes the genes produce) express themselves, including a cellular detoxification enzyme called NQO1. In order to protect cells from potentially harmful agents, NQO1 uses NADH, resulting in lowering of cellular concentrations and an improved NAD+ : NADH ratio. Upregulating the Nrf2 → NQO1 pathway is the next piece of the puzzle. It’s part of addressing programmed aging.
A host of substances have evidence of boosting Nrf2 which are found in Eternus, such as R-Lipoic Acid (R), rosemary extract (R), french grapes extract (R?)

3) Elevates ATP Levels

Adenosine triphosphate, or ATP, is a cell’s “energy carrier” or “energy store” molecule. This is true of eukaryotic and prokaryotic cells, although the ATP production mechanism differs across the two types. ATP is the main source of energy for most cellular processes.
Low ATP levels are often found in people suffering from Chronic Fatigue Syndrome (R), and even moderate depletions of ATP have been linked to sizable increases in oxidative stress (R), while higher ATP levels have been correlated to increases in muscle mass (R) and increased capacity during high intensity activities (R).
Many ingredients in Eternus have been associated to increasing ATP levels including CoQ10 (R), and Eternus contains elevATP® specifically for that purpose, which contains a combination of trace minerals from ancient peat, including ionized magnesium and apple polyphenols, which has been correlated to increased ATP output in clinical studies (R).

4) Upregulation of Sirtuins

Sirtuins are a family of proteins critical to healthy aging. The regulate cellular health by performing critical biologic functions such as DNA expression.
When proteins are undergoing stress, acetyl groups are added to proteins as a response to changes induced by inflammation and oxidation.
Sirtuins remove these acetyl groups to keep the protein in service longer than usual, while simultaneously stabilizing the charge state of the carbon backbone in protein to resist any further changes in their shape. This allows your cellular proteins to live longer and you can save energy on other processes.
Sirtuins such as SIRT1 protects us from nitric oxide. When you have good SIRT1 levels and activity, nitric oxide will stimulate DNA repair genes (via deacetylation of FoxO1). Otherwise, nitric oxide will stimulate genes that will cause the cell to self-destruct (R).
Sirtuins play a major role in good sleep as well. SIRT1 regulates the strength (amplitude) and the duration of circadian gene expression in the retina by removing acetyl groups from key circadian clock regulators, such as BMAL1 and PER2.
In aged mice, SIRT1 levels in the SCN (circadian command center) are decreased, as are those of BMAL1 and PER2, causing a longer circadian period, a more disrupted activity pattern, and an inability to adapt to changes in the light entrainment schedule. Young mice lacking brain SIRT1 have similar effects to these aging-dependent circadian changes, whereas mice that overexpress SIRT1 in the brain are protected from the effects of aging (R).
Anything that increases NAD+, will increase SIRT1 activity. The relevant ingredients in Eternus which have already been listed to that end, but additionally, there is evidence that SIRT1 and SIRT3 activity increases from supplementation with lipoic acid,also found in Eternus, appearing to do so directly (R).

5) Activation of AMPK

AMPK(5′ AMP-activated protein kinase) is an enzyme that plays a key role in energy balance. All creatures from yeast to humans have this enzyme (R).
AMPK can detect the level of energy (number of ATP molecules) in a cell and helps regulate responses when it gets too low or high.
AMPK is produced in a number of tissues, including the liver, brain, fat cells and muscle (R).
AMPK in the hypothalamus senses our level of energy production in the body (energy in the form of ATP). It increases energy expenditure and can also increase appetite (when increased in the hypothalamus) (R).
When cellular energy is low, AMPK is activated and targets a range of processes, the net response of which is an increase in energy production and a coordinated decrease in energy (ATP) usage (R).
AMPK also inhibits the production of fatty acids, cholesterol, and triglycerides, and instead stimulates fat breakdown (R).
A multitude of ingredients in Eternus have been correlated to increasing the activation of AMPK, including Carnitine (R), gynostemma (R), CoQ10 (R), and resveratrol (R).

6) Support for Insulin Regulation

If you are insulin resistant, your brain will not get the message that insulin is trying hard to convey (that you have high levels of sugar in your bloodstream). In this way, insulin resistance promotes hunger. You eat and insulin is released, but your body tells you to eat some more despite the ability of insulin to act as a satiety hormone. Hence why obesity is linked to brain insulin resistance (R). 
When rats had their brain insulin receptors removed, they ate more, developed insulin resistance, and became obese (R). There is a correlation between insulin resistance and fat accumulation in the liver (R). Beyond a weight loss regimen and regular exercise, both of which can decrease insulin resistance, there are a number of supplement foods found in Eternus which can aid in this as well, such as magnesium (R),resveratrol (R),and lipoic acid (R).

What Makes Eternus A Unique Cell Energy and Aging Formula?

1) Comprehensive Targeting of Multiple Processes that Underlie Cell Energy & Aging

The white paper on Eternus lays out a very balanced, multi-pronged strategy in this formulation for addressing not only the 6 categories listed in this review, but also an accounting for the sub-categories and considerations comprising them. The scientists and medical professionals behind Eternus mapped out all the factors that affect cell health and aging to ensure their formulation addresses them all.

2) Synergistic Ingredients

Synergy is when a combination of ingredients produce an effect greater than the sum of its parts. Many ingredients in Eternus have more than a single positive effect and when you stack them together, some effects become stronger than when they are taken separately.

Eternus Ingredients

The Eternus formulation transparently lists all 38 ingredients comprising it and the dosing of each is consistent with the amounts the benefits that warrant their inclusion.

Positive Subjective Effects From Eternus

You can notice very significant improvements from Eternus within just a few days, such as:
- Noticeable increases in energy and vitality.
- Decreases in brain fog and more sustainable mental energy.
- Quicker recovery times from workouts and activities.
- Decreased pain and discomfort from decreased inflammation.
- Improved sleeping quality and easier transitions to wakefulness.

Bad Side Effects

Common negative side effects include:
- Possible upset stomach if Eternus is not taken with food.
- Potential restlessness if Eternus is taken late in the day.

Who is Eternus For?

Eternus is for anyone looking to maximize nutritional support for cell health and cell energy, particularly for those who are looking to delay the onset of age related decline as significantly and comprehensively as can be done through premium nutrition.The product comes with a 100-Day money back guarantee, and significant subjective improvements to vitality and energy are felt by most within the first week, providing quick evidence that cellular energy and efficiency is improving.

Buy Eternus

You can try Eternus by clicking here. Choosing the subscription option (which you can cancel anytime) gets you 50% off the first month supply, and using coupon code LONGECITY gets you an additional 15% off your first purchase.
A comprehensive cell energy product like Eternus can be a tremendous compliment to the foundations of good diet, exercise, and sleep, in holding back the hands of time for as long as possible, and sustaining a high physical and mental quality of life for decades to come.

Since our founding in 2003 as a small a non-profit community forum we have been excited to watch the emergence of the SENS approach and Foundation leading the fight against the blight of involuntary death. While originally dismissed as ‘too radical’ many of the strategies proposed by Dr.deGrey have since gained widespread recognition in scientific circles. 
The MITOSENS approach has always been among the most ambitious ideas and therefore in special need of community funding. LongeCity is proud to have been the first to organise such funding in 2013 and to contribute to the Lifespan.io inaugural fundraiser for the team in 2015. 
Based on the breakthrough results from these projects, MITOSENS is now on the verge of establishing conclusive proof of principle for the strategy. 



To support this effort, LongeCity will 

A. match any donation up to $1000 by an Immortality Institute member. 
Members who made a donation please post here.    

and 

B. contribute to the fundraiser 
• $30 for a tweet by anyone mentioning @longecity_org and the fundraiser*
• $30 for a post by anyone on the LongeCity facebook page* 
• $300 for each MOUSE 'bought' here with LongeCity ‘community points’
• $800 for each new member of the Immortality Institute (reply ‘mitosens’ to the introductory email)
• $1000 for a new quiz accepted at LongeCity (send us a PM when the quiz was created) 

*(one per person - we'll monitor our twitter/facebook accounts and keep a tally)

Support in each case is at the sole discretion of LongeCity and subject to remaining funds in our community budget.

"Biomarkers of Aging Self Experimentation (BASE)"

This is our current flagship programme in this field. BASE’s goal is to better comprehend aging interventions over time and present this data in a useful way.
We are inviting participants to contribute age biomarker data alongside information about their lifestyle and nutrition.
To participate, anyone may complete the BASE Questionnaire anonymously. Qualifying participants may claim a partial reimbursement. 
Results will be shared internally among participants, with a view towards generating an open source database.
The initiative is at an early stage - parameters are likely to change and we are very open to feedback.
⇒ https://www.longecity.org/base/


"Aging Biomarkers"

We all know that biologically and medically, people age at different rates. Understanding why could be a key part in retarding or reversing aging. However, measuring biological age is far more complicated than counting chronological age. In recent years various new methods have been proposed. 
In 2018 LongeCity started a programme supporting our Members in gaining experience with these tests by granting a subsidy for procuring these tests from selected service providers on the condition that the Members self-report the results and their experiences ⇒ on our internal forum. (link) 
We remain very interested in evaluating new biomarkers of aging. We will follow the results of this initiative and support others like the ⇒ AGEMETER tool.    


"N=1 Experiments" 

Since our founding, this site has attracted individuals who are impatient for the state of medical consensus to advance and are experimenting with supplements, techniques and experimental compounds. This has many pitfalls: first and foremost the risk to the individual, the flavour of chasing ‘magic’ that has always tainted the life-extension field, along with the dreadful folly of ‘testimonials’; the risk of generating the flawed impression that taking life extending supplements must somehow be ‘felt’ quickly; a turning away from the principles of scientific equipoise and the hard truths of evidence-based medicine.
Nonetheless this self-experimentation goes on and has some aspects that are worth celebrating: the intensive and personalised engagement with scientific evidence; the assumption of individual responsibility for health and wellbeing; the ongoing adventure of discovery that would not be possible without plenty of risk-takers. To be clear: Faced with these perspectives, LongeCity as an organisiation maintains absolute neutrality. We do not in any way encourage or promote self-experimentation, nor do we condemn and suppress evidence of it. We do however, wish that some ‘self experiments’ were more responsibly planned, conducted, and reported with a view towards generating the most reliable dataset possible. We have therefore set aside some potential funding to complement those experiments that have the potential to yield insights that could be of generalisable interest to the LongeCity community. 

Generally, the scheme works as follows: 
- An individual (the Subject) develops a supplement or other regimen based on an informed review of the literature, community advice and the available sources. 
- The Subject develops a testing plan that assesses meaningful metabolic parameters at meaningful intervals. 
- The Subject commences the regimen. The Subject pays for all supplies and the baseline test which must be published on LongeCity in annonymised form. 
- LongeCity can be approached to pay for a subsequent test. This does not entail an endorsement of the experiment but simply a desire to further asses some of the safety and efficacy parameters in question.
If you want to participate in this initiative, please ⇒ contact us.

The 18th-century Age of Enlightenment brought forth a paradigm shift in perceptions of the human condition and potential. The thinkers of the Enlightenment systematically articulated the case for rationality, science, and technology dramatically improving human well-being and overcoming what were previously considered to be immutable limitations. Those of us today who support the pursuit of indefinite life extension, rejuvenation biotechnology, and emerging research and its applications in a wide array of transformative fields are essentially continuing the project that the Enlightenment philosophers began. Although they had a much more rudimentary toolkit at their disposal, the most visionary minds among them were remarkably able to anticipate many aspects of our contemporary world and even to see beyond it. 
One such individual was Marie-Jean-Antoine-Nicolas de Caritat, Marquis de Condorcet (1743-1794), among the most talented polymaths, philosophers, economists, political scientists, mathematicians, administrators, and authors of the 19th century – a man who unfortunately lived far ahead of his time and whose life was claimed by the tumult of the French Revolution in 1794. Condorcet died in prison under mysterious circumstances, after running afoul of the murderous Jacobin faction that seized power in 1793-1794 and perpetrated a Reign of Terror that subverted the ideals of the Enlightenment. Shortly beforehand Condorcet completed a work that set forth the blueprint for human progress to come – the Esquisse d'un tableau historique des progrès de l'esprit humain (Outlines of a historical view of the progress of the human mind), published posthumously in 1795. At the end of this work, Condorcet briefly but insightfully articulated much of the terminology and conceptual framework that characterize many thoughts in the life-extension movement today. 

Condorcet divides human history into ten epochs, the first nine of which bring the human species to the era of the French Revolution; the tenth epoch is Condorcet’s vision for humankind’s future. Much of what Condorcet articulated has already come to pass – including dramatic improvements in agricultural and industrial processes, broadening of education, major progress toward gender equality, and decreases in the average number of children per family as economic development, education, and living standards have improved. Condorcet even posited an early version of what is today known as the “law of accelerating returns” (a phrase popularized in our era by Ray Kurzweil):

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All the causes which contribute to the improvement of the human species, all the means we have enumerated that insure its progress, must, from their very nature; exercise an influence always active, and acquire an extent for ever increasing. The proofs of this have been exhibited, and from their development in the work itself they will derive additional force: accordingly we may already conclude, that the perfectibility of man is indefinite. (Condorcet 289-290)

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Regarding improvements in longevity, our era already features some of the developments that Condorcet anticipated. In Condorcet’s time, most people still did not die of biological “old age”; average life expectancy in France remained below age 30 for much of the 18th century (ref), and rich and poor alike often fell victim to infectious diseases, warfare, political turmoil, and poor lifestyle habits before reaching any advanced age – and high rates of reproduction accompanied (and were in part motivated by) devastatingly high rates of infant mortality. For Condorcet, bringing average life expectancies into the late seventies and early eighties, as is the case for virtually all “developed” countries today, would have constituted astonishing progress. Condorcet focused first on the major proximate causes of mortality in his time – malnutrition, lack of sanitation, poor living conditions, unhealthy work environments, and life-shortening vices – including lack of physical exercise and the indolence that he associated with the luxury of the aristocracy. Regarding the overcoming of these perils, Condorcet observed: 

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This law [of the perfectibility of organic life] extends itself to the human race; and it cannot be doubted that the progress of the sanative art, that the use of more wholesome food and more comfortable habitations, that a mode of life which shall develop the physical powers by exercise, without at the same time impairing them by excess; in fine, that the destruction of the two most active causes of deterioration, penury and wretchedness on the one hand, and enormous wealth on the other, must necessarily tend to prolong the common duration of man’s existence, and secure him a more constant health and a more robust constitution. (Condorcet 290)

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The methods of human rationality, as directly accessible to the mind and capable of being implemented through societal reforms, could achieve the kinds of lifestyle-related improvements Condorcet described. But he ventured further to address the even more significant potential lifespan extension that medical progress could unlock: 

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It is manifest that the improvement of the practice of medicine, become more efficacious in consequence of the progress of reason and the social order, must in the end put a period to transmissible or contagious disorders, as well to those general maladies resulting from climate, aliments, and the nature of certain occupations. Nor would it be difficult to prove that this hope might be extended to almost every other malady, of which it is probable we shall hereafter discover the most remote causes. (Condorcet 290-291)

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Condorcet’s prognostications directly address the question of what will remain once the most proximate 18th century causes of death and disease (infections, poor climate, bad working conditions) are greatly diminished. In our time, this has essentially happened, and heart disease, cancer, and degenerative illnesses of the brain have become the most common killers (and even the rates of death from some of these ailments are in decline). Condorcet’s contemporaries did not understand the causes of these then-rarer ailments (since most did not live long enough to get them), but we now know them all to be consequences of the degenerative processes of biological aging at the cellular and molecular levels. Condorcet recognized that the mindsets and methods of Enlightenment rationality could be applied to identify and defeat these maladies as well – and the outcome would be indefinite longevity:

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Would it even be absurd to suppose this quality of melioration in the human species as susceptible of an indefinite advancement; to suppose that a period must one day arrive when death will be nothing more than the effect either of extraordinary accidents, or of the slow and gradual decay of the vital powers; and that the duration of the middle space, of the interval between the birth of man and this decay, will itself have no assignable limit? Certainly man will not become immortal; but may not the distance between the moment in which he draws his first breath, and the common term when, in the course of nature, without malady or accident, he finds it impossible any longer to exist, be necessarily protracted? As we are now speaking of a progress that is capable of being represented with precision, by numerical quantities or by lines, we shall embrace the opportunity of explaining the two meanings that may be affixed to the word indefinite. (Condorcet 291)

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The distinction between “indefinite life extension” as the prolongation of lifespans without a fixed upper bound and “immortality” in the sense of indestructability or invulnerability is important for advocates of longevity today and have been repeatedly articulated to persuade the general public to recognize that the life-extension project is the logical continuation of the improvements in medicine, lifestyle, and environment which have already brought about major lifespan increases during the past two centuries. Condorcet was the first to articulate that distinction; when we speak of indefinite life extension, we are indeed building upon Condorcet’s vision and carrying it forward using the next generation of medical technologies. 

Condorcet did not definitively posit whether or not there is some remoter upper bound to possible lifespans, but he did explore both possibilities: 

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In reality, this middle term of life, which in proportion as men advance upon the ocean of futurity, we have supposed incessantly to increase, may receive additions either in conformity to a law by which, though approaching continually an illimitable extent, it could never possibly arrive at it; or a law by which, in the immensity of ages, it may acquire a greater extent than any determinate quantity whatever that may be assigned as its limit. In the latter case, this duration of life is indefinite in the strictest sense of the word, since there exist no bounds on this side of which it must necessarily stop. And in the former, it is equally indefinite to us; if we cannot fix the term, it may for ever approach, but can never surpass; particularly if, knowing only that it can never stop, we are ignorant in which of the two senses the term indefinite is applicable to it: and this is precisely the state of the knowledge we have as yet acquired relative to the perfectibility of the species. (Condorcet 291-292)

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Whatever other limits, if any, humans might come to face if they live centuries or longer, Condorcet convincingly demonstrates that we will never be certain that such limits have been reached – so the possibility of indefinite longevity and the striving toward it are always the appropriate working hypothesis and practical approach. Condorcet’s empirical prediction, which has held true thus far (with temporary aberrations in times of major warfare or societal turmoil), is that mean life expectancy will continue to increase without end:

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we are bound to believe that the mean duration of human life will for ever increase, unless its increase be prevented by the physical revolutions of the system; but we cannot tell what is the bound which the duration of human life can never exceed; we cannot even tell, whether there be any circumstance in the laws of nature which has determined and laid down its limit” (Condorcet 292).

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It is fitting for Condorcet to conclude his treatise – the last work of his life – by pointing to a gloriously open-ended future, where the same miseries and oppressions that shortened his own life need not befall future generations. A great mind born too soon, Condorcet could not prevent his own death but could bestow a vision for us to implement:

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This sentiment is the asylum into which he retires, and to which the memory of his persecutors cannot follow him: he unites himself in imagination with man restored to his rights, delivered from oppression, and proceeding with rapid strides in the path of happiness; he forgets his own misfortunes while his thoughts are thus employed; he lives no longer to adversity, calumny and malice, but becomes the associate of these wiser and more fortunate beings whose enviable condition he so earnestly contributed to produce. (Condorcet 294)

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Many in life extension may feel called by this heroically ambitious, boldly optimistic project for the transformation of humankind – whose epitome and, indeed, the central aim, is the extension and expansion of lifespans without bounds.

Background

LongeCity.org has long been a hotbed of information exchange and discussion about various methods of slowing or reversing the process of aging. An incredible number of supplements have been tried, exercise routines employed, and eating patterns explored.
Is it any of it working? Have LongeCity members succeeded in slowing aging and remaining healthier than their contemporaries?
Precious few people maintain a regular schedule of objective testing for health and aging biomarkers. Even fewer make those results public. LongeCity aims to change this state of affairs. 
In order to foster a ‘citizen scientist’ culture of objective self-monitoring and knowledge sharing LongeCity is supporting all Immortality Institute Members in procuring tests for next-generation biological age markers.


Which tests are supported?

Generally, tests that rely on epigenetic aging markers to give a ‘biological age’ profile and are easily obtainable through reputable third-party testingproviders.

    Currently the following commercially available tests are supported:
     • Epimorphy (https://www.mydnage.com/)
     • Osiris Green (https://www.osirisgreen.com/)
     • TeloYears (https://www.teloyears.com/)

While these tests fit the above description, they are quite different in what they measure. Make sure you use the resources on longecity and elsewhere to make an informed decision which test to choose. Further reading.
Currently our subsidy programme combined with a provider discount means that one of these tests is available to Immortality Institute Members for free or at a substantial discount.
Members can suggest other tests to be included in the list. Contact us with suggestions and references.


Steps for Participants

STEP 1. You need to be a Member of the Immortality Institute. (If you are not yet a member - it may well be worth joining since the discount for the test more than covers your membership donation.)

STEP 2. Register your interest here. (Do not just go and order your test! Wait until you get the ‘all clear’and discount code from the Membership Secretary via forum PM.)

STEP 3. Order the test from the provider using the discount code provided. (Please note that this will involve paying the provider upfront and making sure that you collect your biological samples as instructed and mail them back to the provider) 

STEP 4. Post your results here. The minimum information required is your real (calendar) age and your biological age as determined by the test. However, we’d really like you to share as much information as you think may be pertinent regarding lifestyle, diet, supplementation etc. that might shine a light on your results for further analysis. You don’t have to disclose your name and address).

STEP 5. LongeCity will reimburse you the costs of the test up to a maximum of $150 via paypal to your registered email address.

Note The support programme is a voluntary community effort. Particants in the programme do so at their own risk and responsibility. Any arrangements with third party testing services are private contracts between the service providerand the individual participants. LongeCity makes no guarantees regarding thequality, safety and reliability and utility of any third party tests. Financial support is provided at LongeCity's sole discretion, is not guaranteed and subject to available funds.