Longevity tips and AI startups

Aging

Aging (spelled ageing in British English) is the process of becoming older, that involves a series of functional changes that appear over time and are not the result of illness or accident, but occur as a consequence of accumulating disorders in the body’s structure and functions. It is an unpreventable chronological, social and biological process and is genetically determined and environmentally modulated. Let's see now how aging and life expectancy are affected.

In the case of mammals, life expectancy varies hugely and it ranges from 3–4 years in small rodents to as long as 150–200 years in bowhead whales. As for us humans, we can potentially live for one hundred and twenty years, and just now an international research team has identified more than 2,000 new genes linked to longevity in humans (linked to DNA repair, coagulation and inflammatory response) during an evolutionary comparative genomic study that included 57 species of mammals.

As a matter of fact, different people or different cultures, age at different rates and some tend to age more gracefully than others simply because of their genes and their environment.

But aging is also about time and time perception. Time perception is a construction of the brain. How fast we perceive time to be passing - or mind time - can be manipulated or distorted, and five minutes can be perceived as eternity or just seconds depending on how we feel. 

But what is time?

Time is the indefinite continued progress of existence and events that occur in an apparently irreversible succession from the past, through the present, to the future.

But, while most people think of time as a constant, physicist Albert Einstein showed that time is an illusion. Also according to theoretical physicist Carlo Rovelli, passing time is an illusion: our naive perception of its flow doesn’t correspond to the physical reality. Basically, more and more physicists believe that past, present and future coexist.

They believe that “every moment is co-creating every other moment both forward and backward in time”, meaning that the past influences the future and the future influences the past in an endless feedback loop.

So, if

• “passing time is an illusion”,
• “time perception is a construction of the brain” and
• “every moment is co-creating every other moment both forward and backward in time”…

can we say that our only way out of this loop is by influencing our “future” with thoughts of longevity (i.e. “Can I live to be 150?”), that would eventually “make” our “future” “accept” a mutation that will change our perception of time or/and that will make us more resistant to oxidative stress…so we can live longer?!?

In the end, it is just a mind game and if you think about it, past, present and future actually do coexist. It is just our brain that defines a chronological order and accepts a life span of 70-85 years as normal.

And as Søren Kierkegaard beautifully stated: 

“If you name me, you negate me. By giving me a name, a label, you negate all the other things I could possibly be”.

Anyway, leaving behind us this endless loop of time (whatever time is) and going back to aging, our chronological age (number of years that have passed since we were born or trips we've made around the sun) can differ significantly from our actual biological age (how well we’ve held up during those trips). In fact, the biological age, regardless of how many years ago we were born, occurs as we gradually accumulate damage to various cells and tissues in our body.

For example last year Deep Longevity - a biotechnology company that came out of stealth from Insilico Medicine - anounced that it has developed a new AI system that can predict an individual’s biological age more accurately than conventional methods. Deep Longevity’s team invented the industry’s first-ever aging clock using deep neural networks, by analysing millions of anonymised samples from multiple data types - from blood biochemistry, cell count, protein-coding genes to gut bacteria - and identified aging-related biomarkers for diseases like diabetes, sarcopenia and Nonalcoholic fatty liver disease (Via BusinessWire).

Moreover, the fact that the chronological age and the biological age can differ so much, is probably the indication that the process of aging can be “manipulated” in relation to time or genes or environment or all together. And this “manipulation option” we have, creates a gap where lies our ability to change aging.

In fact, between the question "How long are you going to live?” and the response “I am gong to live 80 yrs!”, there is a gap.

In that gap is our power to choose a new response: "I am going to live 150 yrs".

In our "updated" response lies our growth and our freedom from the physical constraints of our physical reality (Viktor E. Frankl).

And just this week, the newly-created Longevity Science Foundation (based in Switzerland), that plans to extend the human lifespan to more than 120 years, announced channeling over €860M ($1B) into early-stage geroscience research in the next decade. The Longevity Science Foundation will prioritise four areas of research: personalized medicine, therapeutics, AI and predictive diagnostics.

Aging Journey

Let’s begin now this fascinating journey of aging by looking at what is happening inside our cells by following the nine hallmarks of aging (that will give rise eventually to different aging dependent pathologies) - and some potential AI solutions to the aging problem.

1) As we grow old an accumulation of genetic errors due to genomic instability (high frequency of mutations) are accumulating in different parts of our body, contributing to our aging. 

For this reason, headquartered in Toronto, Deep Genomics uses AI and ML to develop life saving drugs by combining DNA, biomarkers and cell machinery. Since its founding in 2015, Deep Genomics has built several predictive systems known as the AI Workbench, and has made billions of predictions across the entire human genome, for millions of genetic variants, and hundreds of millions of novel compounds. On July 28, 2021, they announced the closing of a $180 million Series C financing round, to further validate the significant advances in their AI discovery platform. Moreover, Deep Genomics uses AI and ML to program and prioritise RNA therapeutics for genetic diseases.

2) Telomeres, the nucleotides that live at the end of our chromosomes, are in charge of how quickly our cells age and eventually die, and they are one of the most on the spot indicators of a person’s biological age. So, keep an eye on your telomeres.

On September 28, 2021, Genomic Vision announced the launch of TeloSizer®, for precise detection and quantitative measurement of telomere length. The new TeloSizer service is built on Genomic Vision’s proprietary technology FiberSmart®, of AI automation analysis, to automatically detect, grab images and quantify telomere length on single DNA molecules.

3) Also epigenetic alterations - genes are turned on or off by changing the chemical structure (methylation) of DNA but not changing the DNA coding sequence - have been shown to be correlated with many aging diseases, including autoimmune disorders, neurological disorders as well as Huntington, Alzheimer's, Parkinson's diseases and schizophrenia.

For example, Alzheimer’s disease (AD) is influenced by both genetic and brain epigenomic alterations and Multiple array-based Epigenome-Wide Association Studies - EWASs have identified robust brain methylation changes in AD. For, this reason a group of researchers have developed EWASplus, a computational method that uses a supervised machine learning strategy to extend EWAS coverage to the entire genome. And they have found that genes top in EWASplus loci are enriched for kinases and for genes with evidence for physical interactions with known AD genes (Via Nature July 2021).

For more about epigenetic-startups, StartUs Insights Discovery Platform, a Big Data and AI powered platform covering 2.093.000+ startups and scaleups globally, highlights here the 5 Top Epigenomics Startups out of 170.

4) As we age our mitochondria - that is the powerhouses of our cells - start to decline, and this mitochondrial dysfunction brings lack of energy (ATP). Loss of mitochondrial function is often a sign of aging and other age-related health problems, while on the contrary maintenance of mitochondrial fitness is linked to increased healthspan and longevity.

In 2020, Astellas has acquired the UK Nanna Therapeutics for €80M to boost the development of anti-aging drugs. Through this deal, Astellas will gain access to Nanna’s drug discovery technology - which focuses on drugs that target the mitochondria - developing a treatment for a genetic syndrome called "mitochondrial encephalopathy, lactic acidosis and stroke-like episodes", or MELAS (caused by a change in one of several genes that help build mitochondria, cell structures that convert food into energy). Nanna’s microfluidics-based drug discovery technology was a big attraction for Astellas, since with their high-throughput platform, Nanna can generate, screen and acquire data on billions of small molecules in parallel, producing drug candidates in a matter of months rather than the years it typically takes.

On March 04, 2021, a paper was published on Nature for a ML-based classification of mitochondrial morphology in primary neurons and brain (primary cortical neurons from transgenic mice). This is a semi-automated image analysis for the quantitation of mitochondrial morphology for both in vitro and in vivo applications.

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Telomere damage, epigenetic dysregulation, DNA damage and mitochondrial dysfunction are primary drivers of damage in aging, that can induce senescence. 

Senescence can in turn drive aging in response to damage: stem cell exhaustion and chronic inflammation. Other responses to damage, such as proteostatic dysfunction and nutrient signaling disruption, are also integrally linked with the senescence response.

So, let’s talk about cellular senescence (and immuno-senescence) now.

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5) Normally the body removes the problematic cells with genetic errors via apoptosis (with the help of the immune system), but unfortunately some cells evade apoptosis, taking up space in the tissue. These cells are known as senescent cells, and they pump out pro-inflammatory signals which together form the SASP (senescence-associated secretory phenotype), that is thought to significantly contribute to aging and cancer, by damaging the local tissue. Thus, senolytics (a new class of drugs for the destruction of senescent cells) and the removal of the SASP are a potential strategy for promoting health and longevity.

Professor Shinsuke Yuasa from Tokyo has been focusing on AI drug development in Longevity for many years, by utilising convolutional neural networks (CNN) – deep neural networks commonly applied for visual imagery analysis that expresses how one shape is modified by another. One of it's most recent breakthrough is the development of DeepSeSMo, a CNN based scoring system that was trained to quantify the number of senescent cells based on biological microscopy slides, since they have distinct morphologies with enlarged and flat cell bodies and distinct aggregation heterochromatin, a tightly-packed form of DNA.

This algorithm was tested on tissue treated with various drugs in an attempt to find senolytic or senotherapeutic drugs and four targets were identified: terreic acid, PD-98059, daidzein and Y-27632·2HCl (via Longevity Technology).

In particular,

• the terreic acid (a metabolite with antibiotic properties produced by the fungus Aspergillus terreus) extends yeast’s lifespan,
• the PD-98059 (an inhibitor of mitogen-activated protein kinase kinase) and daizein (a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones) suppresses cellular senescence and associated phenotypes, and
• Y-27632·2HCl (a selective p160ROCK inhibitor) regulates the cell cycle more generally.

Moreover, investigators at Stanford University School of Medicine and the Buck Institute for Research on Aging just published their findings in a paper titled: “An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging” (July 2021). They claim that by using AI they can build an inflammatory-aging clock-iAge predicting how strong or not our immune system is (immune-senescence), since standard immune metrics used to identify individuals most at risk for developing single or even multiple chronic diseases of aging are lacking.

So, while the immune system is important for fighting deseases, it was only in the past few decades that it has become apparent that inflammatory components of the immune system are often chronically elevated in aged individuals and associated with an increased incidence of cancer, cardiovascular disease, neurodegenerative disorders, and this have led to the concept that inflammation plays a critical role in regulating physiological aging.

6) Another thing to “control” during aging is the mechanism in charge of quality control for protein synthesis (proteostasis). Proteostasis means that we have biological pathways within our cells that control the biogenesis, folding, trafficking and degradation of proteins. Any dysfunction in proteostasis can arise from errors in any of the above steps.

On August 24, 2020, Yumanity Therapeutics (a clinical-stage biopharmaceutical company that is accelerating the revolution in the treatment of neurodegenerative diseases) and Proteostasis Therapeutics (a clinical stage biopharmaceutical company developing small molecule therapeutics to treat diseases caused by dysfunctional protein processing) announced that they have entered into a merger agreement, to leverage their common scientific expertise in protein misfolding (Source). Yumanity’s drug discovery platform is designed to enable a rapid screening for potential disease-modifying therapies by overcoming toxicity of misfolded proteins in neurogenerative diseases.

7) Nutrient sensing - cells ability to recognise and respond to fuel substrates such as glucose - is also gradually declining as we age. Current evidence indicates that increased nutrient signalling accelerates aging. While decreased nutrient signalling - achieved with caloric restricted diets - is promoting healthspan and longevity.

On May 2021, Gero announced GeroSense AI to track biological age and resilience via smartphone sensor data. GeroSense is a health app on our smartphone that provides digital biomarkers of health and resilience (the recovery rate after stress such as having a cold, exhausting physical activity etc.). But instead of simply counting the total number of steps taken each day, GeroSense predicts biological age acceleration in years of life gained or lost, due to healthy or unhealthy lifestyle and nutrition choices (Source).

8) The decline in regenerative capability of different tissues with aging - along with a significant reduction in the number, proliferative capacity or differentiation potential of distinct stem cells - has led to the idea that aging is due, at least in part, to the loss of functional adult stem cells needed for tissue repair.

For example, Cellino Biotech is using a unique blend of lasers and ML to transform the manufacturing process of stem cells. They are the only company using this approach, and that convergence lets them produce stem cells in a scalable way for the first time. Cellino uses image-guided ML to characterise the highest quality stem cells. They want to live in a world where it’s possible to make therapies derived from our own stem cells and tissues (because they don’t require immunosuppression), so in order to achieve their goal, they are pursuing collaborations with cell therapy developers to move programs through the clinic very quickly (Source).

9) Finally, altered intercellular communication is another of the integrative hallmarks of aging, but is mainly caused by other hallmarks, particularly cellular senescence and inflammation.

On October 4, 2021, a review on GlyNAC (a combination of Glycine and N-Acetylcysteine) supplementation as a novel nutritional approach to improving declines associated with aging was published, analysing published research on the effects of GlyNAC supplementation on various components of aging, and concluded that emerging evidence supports that GlyNAC could play a role in the overall health of humans as they age (Source).

In particular, emerging evidence from human studies shows that GlyNAC influences five of the nine hallmarks of aging, including mitochondrial dysfunction, altered intercellular communication, dysregulated nutrient sensing, genomic toxicity and cellular senescence.

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