Highlights from longevity research, trials and funding in January 2021
Hundreds of companies are working to develop treatments to slow down aging and increase healthy longevity.
Researchers are publishing important advances, scientists are reporting remarkable results in clinical trials, and companies are raising significant funding.
This article includes highlights from longevity research, clinical trials and funding published in January 2021.
In 2020 MIT Technology Review selected Anti-Aging Drugs as one of 10 Top Breakthrough Technologies expected to make the biggest impact toward solving the most important problems facing humanity. Although no longevity therapeutics have gained regulatory approval yet, promising potential drugs have passed phase I and II clinical trials and some are in phase III clinical trials. Some of these therapeutics may be granted approval and become available within five years. Research is underway in many areas of aging and we expect a series of near-term breakthroughs. Current progress in aging research, complemented by increases in funding, could deliver significant near-term treatments and aging without illness could become a reality in our lifetime. Over the coming months I will explore important advances in the longevity industry in Longevity Technology. These are ten companies and organisations that I’m looking forward to writing about in 2021.
For thousands of years, doctors and indigenous healers have treated disease by adding molecules to people’s bodies in the form of pharmaceuticals, herbs and nutrients. Today a pioneering nanomedicine company is taking a very different approach. Nanomedicine company NaNotics is building subtractive nanoparticles called NaNots to deplete pathogenic targets from the human body – without adding molecules. NaNots are biochemically programmed to absorb pathogenic targets and then excrete them from the human body. They can be programmed to absorb specific targets that drive diseases ranging from cancer to sepsis to aging. NaNots can be thought of as the world’s smallest, most specific, biocompatible sponges.
Oisin Biotechnologies is doing something that would be impossible using traditional pharmaceutical drugs. Their breakthrough gene therapy platform treats disease using a software program written in DNA that can be programmed to kill senescent or cancer cells. Their approach is predicated on the idea that damaged cells “know” that they are damaged – and that this knowledge can be exploited to coax them into killing themselves. In this article I share highlights from their impressive results in mouse studies. 1) a single injection resulted in 90% reduction in solid tumours in 48 hours 2) age-related bone density loss was effectively prevented in male mice 3) treated mice lived 20% longer even when treatment was started in old age 4) after a single treatment senescent cell removal rates reached as high as 70%.
Scientists at the Buck Institute for Research on Aging have published a new study that found that a compound that extends lifespan in worms also slows bone loss in aging mice. These findings are relevant to humans and could lead to interventions that slow decline in tissue and organ functions and protect people from age-related disease. This multi-year study, which involved five labs at The Buck Institute and over 700 mice, provides a treasure trove of data for researchers who are working to develop therapeutics for age-related diseases. In the study, fractures occurred in 2.5% of the mouse population which is similar to the 1-2.7% incidence of hip fractures in humans over age 65. Benzoxazole slowed bone aging by up to 31% over the course of a year’s treatment in the mice. The study was published in the Journal of Bone and Mineral Research Plus.
New research from the Buck Institute for Research on Aging published in Cell Reports provides new insights into the immune system and opens up possibilities for new immunotherapeutics and a new biomarker of aging. The paper describes how mechanical force primes and likely controls immunology during acute and chronic disease because it readies the immune system in the face of danger. The association between tissue stiffness and aging is well known. For example, as people age their lungs and the blood vessels in their lungs become stiffer. Some people’s lungs double in stiffness as they age. This research suggests that tissue stiffness may initiate an inflammatory loop that leads to chronic inflammation which accelerates biological aging and drives many age-related diseases, and the genes that are activated via cellular tension are potential targets for immunotherapeutics.
This is a special issue of eLife with recent breakthroughs in aging research and interventions that extend longevity. 1) Rapamycin rejuvenates oral health in aging mice 2) Mortality: The challenges of estimating biological age 3) Aging: Searching for the genetic key to a long healthy life 4) Longitudinal trajectories, correlations and mortality associations of 9 biological ages across 20-years follow-up 5) Pan-mammalian analysis of molecular constraints underlying extended lifespan 6) Germline burden of rare damaging variants negatively affects human healthspan and lifespan 7) mRNA decapping is an evolutionarily conserved modulator of neuroendocrine signalling that controls development and ageing 8) Opposing p53 and mTOR/AKT promote an in vivo switch from apoptosis to senescence upon telomere shortening in zebrafish 9) Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity 10) Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice 11) Ovariectomy uncouples lifespan from metabolic health and reveals a sex-hormone-dependent role of hepatic mTORC2 in aging.
Superagers are people aged 80+ who retain cognitive and episodic memory performance equal to people 30 years younger. How does a person become a superager? Studies show that superagers have a significantly thicker brain cortex compared with their same-aged peers. Elucidating the genetic and metabolic factors that drive superagers’ ability to retain exceptional cognitive performance will enable researchers to find novel methods to prevent cognitive decline. Evidence for cognitive aging found in the genes of superagers could provide vital insight into preventing Alzheimer’s disease and dementia.
A new study from the University of Oxford and University College London explores the link between heart health and brain health. 1) arterial stiffening is a marker for increased cardiovascular disease risk, myocardial infarction, heart failure, stroke, dementia, and renal disease 2) arterial stiffness also impacts cognition and dementia 3) researchers investigated 542 older adults, measuring aortic stiffness at 64 years and 68 years 4) subsequent MRI scans assessed size, connections and blood supply of different brain regions 5) the study found that faster aortic stiffening in mid-life was linked to poorer brain health, including a lower brain blood supply, reduced structural connectivity between different brain regions and a worse memory 6) reduced connectivity between brain regions is an early marker of neurodegenerative diseases such as Alzheimer’s 7) preventing these changes by reducing or slowing down the stiffening of our body’s large blood vessels may be one way to maintain brain health and memory as people age 8) medical interventions and changes of lifestyle made earlier in life could help to slow down arterial stiffening.
New evidence brings an already-established alternative splicing mechanism back to light with reignited importance for senescence and human longevity. The removal of senescent cells through senolytic drugs is at the forefront of the longevity market. But there’s a less invasive approach called senotherapeutic interventions. Senotherapeutic interventions aim to prevent cells from entering senescence.
Deep in the labs of the world-renowned Buck Institute for Research on Aging a company is growing. Gerostate Alpha, founded by senior Buck scientists Simon Melov Gordon Lithgow and Mark Lucanic, is focused on the developing new drugs that target aging. Gerostate Alpha has constructed a platform to identify interventions that attenuate or halt multiple aging indications simultaneously to improve healthspan, function, and perhaps even increase lifespan. The company is targeting 6 major areas of unmet medical need: the CNS, muscle decline, pulmonary decline, skeletal decline, cardiovascular, and metabolic. The founders are targeting aging in a very genuine, robust and rigorous way, but they are also targeting it through the prism of commercialisation.
Gerostate Alpha was founded by three senior scientists at the Buck Institute for Research on Aging Simon Melov Gordon Lithgow and Mark Lucanic so the infrastructure has been built up at the Buck Institute over many decades. This would cost tens of millions of dollars if a start-up were to attempt to replicate it. They have already screened small molecule libraries on 60,000 compounds and identified over 30 hits that have been validated. Some of the best hits are resulting in 40% lifespan extension in Caenorhabditis which is high for a pharma intervention. They’re now prepping to move into preclinical mouse models. They’ve had some really interesting hits and they’re conducting follow up experiments on the pathways involved in those and the efficacy of those compounds, in those specific tissues. Gerostate Alpha is currently seeking additional seed funding of $3 million to take the company into 2022, at which point it expects to raise a series A round.
Harvard spin-off Cellvie has closed a $5M seed round led by KIZOO Technology Capital. The company addresses mitochondria dysfunction which has been tied to Parkinson’s, Alzheimer’s, heart attacks, strokes, and age-related degeneration and on ischemia reperfusion injury which occurs when blood flow to a part of the body is interrupted and subsequently reintroduced as in heart attacks, strokes and organ transplantation. The potential of the technology was recently demonstrated in a clinical investigation at Boston Children’s Hospital. Paediatric patients on heart-lung-support after suffering a cardiogenic shock received the treatment to revitalise their heart muscle. 80% of these children experienced myocardial recovery, which compares with an expected 29%. The implications of the findings are ground-breaking and will be published in The Journal of Thoracic and Cardiovascular Surgery.
Two companies in the mitochondrial transfusion space have raised funding: Cellvie has raised a seed round for its therapeutic mitochondria transfer treatment, and Mitrix and secured $250,000 in pre-seed funding to embark on its mission to develop a whole body mitochondrial transfusion technology. Mitrix is the first investment of Ronjon Nag’s R42 Group AI and Longevity Fund, which split the round 50/50 with Petr Sramek’s Longevity Tech Fund. The decline of mitochondria over time is one of the primary factors in aging and their dysfunction is linked to a wide range of diseases, from Parkinson’s and Alzheimer’s to heart attacks and strokes. The idea behind Mitrix is to extract and grow young mitochondria in external bioreactors, and then transfuse them into the body in later life, enabling the regeneration of cells to youthful state. We have blood banks today so in theory we could have mitochondria banks in the future.
Clene Nanomedicine is targeting neurodegenerative disease with gold nanocatalyst technology. The company went public last week. With a unique technology addressing a class of neurodegenerative disease that the World Health Organization predicts will become the second most prevalent cause of death within the next 20 years, Clene is a company on a mission to change how we treat diseases of the brain. The company has several products in Phase 2 and one in Phase 3 trials for diseases including multiple sclerosis, Parkinson’s and amyotrophic lateral sclerosis. Clene completed a $42 million Series D financing last summer. The company was contemplating an IPO in 2021, when the opportunity arose to move more quickly via a SPAC which saw the company go public by merging with Tottenham Acquisition I Ltd. The transaction raised approximately $31.9 million.
Longeveron a longevity biotech company that develops cellular therapies for age-related conditions, filed the first longevity biotech IPO of 2021 with the SEC to raise up to $30 million. The Miami based company is developing cellular therapies to treat specific aging-related and life-threatening conditions. Its lead product, Lomecel-B; this a cell-based therapy derived from culture-expanded medicinal signalling cells which have been sourced from the bone marrow of young, healthy, adult donors. The company is also currently sponsoring Phase I and II trials in Alzheimer’s disease, aging frailty, metabolic syndrome, Acute Respiratory Distress Syndrome and hypoplastic left heart syndrome. The company which was founded in 2014 booked $6 million in revenue in 2020.
Professor Katrin Andreasson, MD and colleagues at Stanford University found that blocking certain interactions on immune cells reverses age-related mental decline in older mice. The researchers have published a new study in Nature, which shows that restoring the metabolism of certain immune cells reverses cognitive decline in aging mice. In the study, manipulation of myeloid cells was able to restore the youthful metabolism and placid temperament of cells in living mice. This process also reversed age-related mental decline in older mice, restoring their recall and navigation skills to those exhibited by young mice. This study suggests that if you adjust the immune system, you can de-age the brain. Experiments on cells in the lab indicate that similar rejuvenation may be possible in humans.
The world of longevity-specific investment funds just got bigger. R42 Group, the investment group of Dr Ronjon Nag, has launched its first fund this week. The R42 AI and Longevity Fund is a $14 million seed fund targeting early stage investments in companies “at the intersection of mathematics and biology.” In this article, we speak exclusively to Ronjon Nag about his first fund, targeting seed investments in Longevity AI and biotech. Ronjon Nag is already well-known for making early investments in longevity, but this is the first time he’s put together a fund.
Turn Biotechnologies announced that it has acquired the global rights for new technology that reprograms cells to undo many of the effects of aging. The company’s epigenetic reprogramming of age ERA technology uses mRNA to deliver transcription factors to the cells’ epigenome which controls cellular activity. The transcription factors – which can be delivered in a variety of combinations to target different cells – revitalise the epigenome and restore the cells’ ability to behave more youthfully. The company licensed ERA technology from Stanford University where it was developed by the three researchers who founded Turn.
This nanomedicine delivery system – with unprecedented penetration across the blood brain barrier – is being developed to treat neurological disorders created by a research team at Brigham and Women’s Hospital and Boston Children’s Hospital. This radically simple approach is applicable to many neurological disorders where delivery of therapeutic agents to the brain is desired it was therapeutically effective and could eventually lead to treatments for numerous neurological disorders. Previous research has identified biological pathways leading to neurological disorders and has developed promising molecular agents to target them as a result. However, translating these discoveries into clinically approved treatments has been hampered by the challenges scientists face in delivering therapeutics across the blood-brain barrier (BBB) and into the brain.
Senolytics is a hot area for longevity investment and Rubedo Life Sciences is clearly a very interesting player in this field. We recently spoke with the company’s CEO and co-founder Dr Marco Quarta to learn more about Rubedo’s origins and where the company is headed. Late last year the company secured a seed funding round of $12 million to develop senolytic therapies that selectively target and clear senescent cells from aged or pathological tissues. The company is now conducting preparatory work for IND-enabling studies, ahead of moving to Phase 1 clinical trials, potentially as early as 2022. Senescent cells are cells that “forget” to die at the end of their lifespan, but remain metabolically active even though they have stopped replicating and growing. They play a key role in the progression of chronic disorders, so targeting and eliminating these cells is thought to have potential for longevity benefits in humans.
A long-awaited AI approach can now be implemented in screening for anti-senescence drug candidates. Professor Shinsuke Yuasa and his team at the Keio University School of Medicine in Tokyo are using AI to develop drugs for healthy longevity. Their most recent breakthrough is the development of DeepSeSMo, a CNN scoring system that was trained to quantify the number of senescent cells based on biological microscopy slides. Their algorithm could further longevity research though elucidation of senescent mechanisms, and since Deep-SeSMo picks up characteristics unique to senescent cells, it can be trained to identify how and when they will arise, as well as exploring the senescence threshold. DeepSeSMo is part of a machine-learning boom within aging research.
The lung has always been known to contain a great variety of cells, but scientists are only beginning to understand exactly how many after a breakthrough study found 14 types of lung cells that were previously unknown to science. It is now hoped the creation of a new, extensive lung map by researchers at Stanford University could pave the way for better understanding and treatment for lung disease as well as, potentially, Covid-19. A team of molecular biologists at Stanford University have created the most extensive map of the lungs ever made. The new lung atlas has broad implications for medicine and provides insight into the functions, regulation and interactions of known and new cell types. This detailed map could hold the key to the creation of new therapies to boost longevity.
This is an article about a study by Professor Leocardio Rodriguez-Mañas and his team at the Fundación para la Investigación Biomédica del Hospital Universitario de Getafe on telomere length, frailty and lifespan. Findings: telomere length lacked association with aging, telomere length lacked association with frailty, telomere length did not predict frailty, telomere length did not predict mortality, frailty was a better predictor of mortality than telomere length, this study suggests that telomere length may not be a reliable biomarker of functional age.
The European Patent Office has granted BioArctic a patent for novel antibodies for Alzheimer’s therapy that could be developed into a treatment for Alzheimer’s disease. The patent focuses on novel antibodies which target pE3-Ab, a specific truncated form of amyloid beta. Monomers of pE3-Ab are highly prone to aggregate, leading to the formation of harmful soluble Ab aggregates which cause debilitating cognitive and other symptoms in Alzheimer’s disease. This patent is good news for Alzheimer’s disease research. More than 30 million people around the world live with Alzheimer’s disease. BioArctic, founded in 2003 based on innovative research from Uppsala University in Sweden, focuses on disease-modifying treatments and reliable biomarkers and diagnostics for neurodegenerative diseases.
The potential longevity benefits of spermidine have already led to a number of supplements appearing on the market. With a strong focus on the science, and on proving the efficacy of its products in humans, Longevity Labs, Inc. is an interesting player in this space. The company seeks to validate efficacy of spermidine supplement through clinical studies. Drawing from scientific research conducted at the University of Graz, Longevity Labs has already launched its first product, spermidineLIFE. The daily dietary supplement is based on a spermidine-rich wheat germ extract that supports cell renewal by regulating autophagy. With an initial study already showing that spermidineLIFE is both safe and well-tolerated in older adults, a clinical study is now being conducted to assess the supplement’s efficacy in patients with cognitive decline. At the core of Longevity Labs’ story is its close ties with the University of Graz, and Professor Frank Madeo, who discovered spermidine’s properties as an autophagy trigger and age-protective substance in 2009. The company was founded in 2016, with the goal of commercialising Madeo’s work.
Finding a protein as a marker for aging could allow for better monitoring of biological age, aid in aging clocks development, and improve our understanding longevity. Protein turnover decreases with age to preserve metabolic costs, especially in longer-lived organisms such as humans. Every protein has a certain lifetime ranging from minutes to years. After a period of time, a protein is degraded and replaced by a newly synthesised version. This cellular process is known as protein turnover (PTO). The PTO of a protein generally depends on the cell type, organism and a plethora of environmental factors. On a cellular level, specific genetic motifs, protein folding state and cellular proteolytic pathways involved define PTO rate. Within the longevity field, there is significant interest in understanding the relationship between changes in PTO, its kinetics and proteostatic distribution during aging. There is evidence suggesting that slower PTO rates may be associated with lower protein quality control and diminished proteostasis during aging.
Professor James Kirkland and colleagues at the Mayo Clinic conducted research to establish if clearance of senescent cells would improve cognitive function. Their proof-of-concept study shows that removal of senescent cells in the hippocampus of mice leads to improved cognitive responses. This opens up a potential therapeutic avenue for alleviating age-associated cognitive impairment. Most neurodegenerative diseases have established correlations with aging, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, so affecting these diseases has an impact on longevity. Senolytic intervention could become a preventative solution to a problem currently lacking successful interventions.