Fight Aging! Newsletter, March 13th 2023

Ageing is associated with increased inflammation and activation of the innate immune system. This condition is known as "inflamm-ageing" and is characterised by chronic activation of JAK-STAT signalling in the circulating immune cells of elderly patients, activation of the NLRP3 inflammasome, and higher circulating levels of inflammatory mediators such as C-reactive protein, IL-6, and fibrinogen. A leading hypothesis for the origin of "inflamm-ageing" is the build-up of senescent cells with ageing, and the consequent production of a systemic senescence-associated secretory phenotype (SASP). An important support for this hypothesis comes from experiments in which aged mouse blood is transferred to young animals, which results in features of accelerated ageing. Interestingly, previous treatment of the old donors with senolytic agents reduced "inflamm-ageing" after blood exchange, and the old blood lost its pro-ageing activity. In humans, senolytic treatments also reduce the "inflamm-ageing" of patients suffering from lung fibrosis or chronic kidney disease.

Importantly, mitochondria of senescent cells are known to play a key role in triggering the SASP. In particular, depriving senescent cells of mitochondrial DNA or mitochondria altogether seriously compromises the SASP. The detailed mechanisms connecting the mitochondria of senescent cells with the SASP are still unknown. We speculate that they could be similar to the mechanisms connecting dysfunctional mitochondria with inflammation. These may include the release of cytosolic and/or extracellular mitochondrial DNA (mtDNA), mitochondrial double-stranded RNA, N-formyl peptides (a sub-product of mitochondrial protein translation), and phospholipid species such as cardiolipin, enriched in the inner mitochondrial membrane . The most studied of these components is mtDNA.

Taken together, the evidence presented in this review shows that mitochondria dysfunctions have a close relationship with ageing and cellular senescence. Several mitochondrial pathways have already been taken into consideration as potential therapeutic targets for ageing-associated diseases, and promising compounds have been developed. Future research will have to answer numerous open questions including: is it possible to completely restore mitochondrial function in senescent and aged cells? Which age- or senescence-associated aspects are the primary drivers of mitochondrial dysfunction and vice-versa? Which ones are targetable therapeutically? Answering some of these questions could get us closer to healthy ageing, with countless medical, social and economic benefits.

Although investments from the private sector are at all-time highs and foundations such as Hevolution and Impetus Grants are committing millions of dollars to aging research every year, the amount of funding that longevity and other preventative healthcare organizations receive is still a far cry from the more traditional fields of medicine. For context, when picking apart the 2023 Presidential Budget Request, a rough measure showing how much government capital is provided to the National Institutes of Health (NIH), and more specifically to the National Institute of Aging (NIA), we found that only 0.54% of the entire NIH annual budget request was dedicated towards Aging Biology.

This week, A4LI, a 501c4 non-profit proudly announced the launch of the Longevity Science Caucus - an initiative, years in the making, to help educate members of Congress about the growing field of longevity biotech and promote initiatives aimed at increasing the healthy average lifespan of all Americans. While there are numerous ways Congress can help propel this industry forward, such as making an easier FDA approval process specifically for longevity medicines, the newly launched caucus will primarily focus on increasing funding efforts to start.

Congressman Gus Bilirakis (R-FL) and Congressman Paul Tonko (D-NY) are proud to announce the formation of the Congressional Caucus for Longevity Science. The "Longevity Science Caucus" aims to educate Members about the growing field of aging and longevity biotechnology, and promote initiatives aimed at increasing the healthy average lifespan of all Americans. Along with Bilirakis and Tonko, Representatives Dan Crenshaw (R-TX), Michael Burgess (R-TX) and Anna Eshoo (D-CA) are founding members of the newly created caucus. "Increasing life expectancy and promoting positive health outcomes are important priorities, and the formation of this caucus is an important step toward achieving those goals. I believe in promoting individual responsibility and supporting innovation in the pursuit of scientific discoveries that will enable Americans to live happier and longer lives. I am honored to co-chair this bipartisan effort with my colleague, Congressman Tonko. We will work with our colleagues in an effort to make a significant impact on the future health and wellness for our constituents."

Aging generates specific changes associated with a process called cellular senescence. This permanent state of cell cycle arrest promotes tissue remodelling during development but leads to the declined tissue regenerative potential and function after injury, and activates inflammation and tumorigenesis in aged organisms. Senescence promotes the production of cytokines, chemokines, proteases, and growth factors some of which are known as senescence-associated secretory phenotype (SASP). Recent studies demonstrates that chromatin is instrumental in regulating SASP and inflammation through the innate immune cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) which can be activated upon DNA sensing.

Inflammasomes are intracellular protein complexes involved in almost all human aging-associated complications such as cancer, cardiovascular, metabolic, and neurodegenerative diseases through the production of interleukin-1β (IL-1β) and IL-18. These protein platforms comprise sensing proteins of the NOD-like receptor (NLR) family, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and procaspase-1. Upon sensing of pathogen-associated molecular patterns (PAMPS) or damage-associated molecular patterns (DAMPS), some NLRs such as NLRP3 and NLRP1 to some extent associate with ASC, a response that leads to the recruitment and activation of the cysteine protease, caspase-1. Active caspase-1 cleaves pro-IL-1β, pro-IL-18, and GSDMD, thereby facilitating the secretion of IL-1β and IL-18 through plasma membrane pores formed by the N-terminal fragments of GSDMD. These pores can also release IL-1α and cause pyroptosis. Despite scientific advances in the biology of the NLRP1 and NLRP3 inflammasomes, the role that these proteins play in senescence remain controversial.

Irradiation of cells or tissues is a widely used model of stress-induced senescence, which we used to determine the role of the NLRP1 and NLRP3 inflammasomes in this process. We found that irradiation induced the expression of NLRP1, NLRP3, and SASP. Notably, inhibition of the NLRP1 inflammasome but not NLRP3 inflammasome attenuated the expression of senescence markers, responses that were GSDMD- and cGAS-dependent.

An appealing alternative to reducing calories may be manipulating dietary macronutrients. Contrary to the conventional wisdom that calories from different sources are equivalent, a number of retrospective and prospective clinical trials have found that eating diets with lower levels of protein is associated with lower rates of age-related diseases including cancer and diabetes, and an overall reduction of mortality in those under age 55. While the effect of long-term protein restriction (PR) on human aging has not been tested in a randomized clinical trial (RCT), short-term RCTs in overweight or diabetic humans has found that protein restriction (PR) promotes metabolic health. Finally, PR diets have been repeatedly shown to increase the healthspan and lifespan of model organisms, including flies and rodents.

We and others have shown that much like calorie restriction (CR), restriction of specific nutrients, including total protein, the three branched-chain amino acids leucine, isoleucine, and valine, or isoleucine alone, can promote lifespan and metabolic health in animal models. While CR is less efficacious when starting in late life, the effects of interventions restricting amino acids in late life on healthy aging is unknown. Here, we investigate the metabolic, molecular, and physiological effects of consuming diets with a 67% reduction of either all amino acids (Low AA) or of isoleucine alone (Low Ile) in male and female C57BL/6J.Nia mice starting at 20 months of age.

We find that both diets reduce adiposity in aged mice; however, these diets decreased lean mass, and did not show significant improvements in frailty or fitness. The glucose tolerance of both male and female mice consuming Low Ile and Low AA diets were improved. We also observed a moderate increase in energy expenditure and respiratory exchange ratio induced by the two dietary interventions. In the hearts of aged female mice, Low Ile reversed age-associated changes in heart rate and stroke volume, returning cardiac function to similar levels as observed in young mice. We found that both Low AA and Low Ile diets promoted a more youthful molecular cardiac profile, preventing age-dependent increases in phosphatidylglycerols. These results demonstrate that Low AA and Low Ile diets can improve aspects of metabolic health in aged mice of both sexes, and has positive effects on cardiac health in aged females, suggesting that these dietary interventions are translationally promising for promoting healthy aging even in older people.

The biological activity of cells and organisms depends on the proper function of many different proteins involved in key cellular signaling pathways. To remain biologically active, proteins need to preserve their native three-dimensional structure and solubility. Any alterations to these parameters challenge their ability to perform their normal biological function, with devastating consequences for the cell and the organism. Previously reported evidence showed a transition to insolubility of several proteins during aging in different models. Interestingly, many of these proteins are predicted to have high propensity to misfold and aggregate, similarly to protein misfolding disorders (PMDs). Based on these observations, we hypothesized that during aging several different proteins undergo progressive misfolding and aggregation to form structures similar to those found in age-related PMDs, causing widespread and chronic cellular dysfunction, which is the hallmark feature of aging.

In this study, we report the extensive and progressive accumulation of misfolded proteins during natural aging/senescence in different models, in the absence of disease. We coined the term age-ggregates to refer to this subset of proteins. Our findings demonstrate that age-ggregates exhibit the main characteristics of misfolded protein aggregates implicated in PMDs, including insolubility in detergents, protease-resistance, and staining with dyes specific for misfolded aggregates. Misfolded protein aggregates with these characteristics are thought to be implicated in some of today most prevalent diseases, including Alzheimer's disease and related forms of dementia, Parkinson's disease, Amyotrophic Lateral Sclerosis, type 2 diabetes, and even cancer. The strongest risk factor for all these diseases is aging, supporting our concept that advanced age is associated with increased accumulation of misfolded protein aggregates.

We found intracellular age-ggregation in the aged brain, where misfolded proteins are sequestered into aggresomes. Aggresomes have been studied in the context of neurodegenerative diseases, where they act as a general defense mechanism against high levels of accumulation of toxic misfolded proteins. Our results indicate that the aged brain contains relatively large amounts of misfolded species, whose soluble versions participate in cellular pathways that play fundamental roles in preserving basic functions, such as protein quality control, synapsis, and metabolism. By comparison with PMD, it is likely that the aging-associated misfolded protein will be non-functional or acquire a toxic activity. Therefore, we speculate that age-related protein misfolding may play a key role in the decline of those processes. Alternatively, the formation of misfolded aggregates might be a consequence of a dysfunctional proteasomal and other degradation pathways. The reproducibility of our results using various different techniques, methodologies, and model systems (invertebrates, cellular models, and rodents) indicate that protein misfolding during aging is not a stochastic phenomenon, but rather that a specific subset of proteins are prone to misfold with age.

Aging is often associated with a loss of cell type identity that results in an increase in transcriptional noise in aged tissues. If this phenomenon reflects a fundamental property of aging remains an open question. Transcriptional changes at the cellular level are best detected by single-cell RNA sequencing (scRNAseq). However, the diverse computational methods used for the quantification of age-related loss of cellular identity have prevented reaching meaningful conclusions by direct comparison of existing scRNAseq datasets.

To address these issues we created Decibel, a Python toolkit that implements side-to-side four commonly used methods for the quantification of age-related transcriptional noise in scRNAseq data. Additionally, we developed Scallop, a novel computational method for the quantification of membership of single cells to their assigned cell type cluster. Cells with a greater Scallop membership score are transcriptionally more stable. Application of these computational tools to seven aging datasets showed large variability between tissues and datasets, suggesting that increased transcriptional noise is not a universal hallmark of aging.

To understand the source of apparent loss of cell type identity associated with aging, we analyzed cell type-specific changes in transcriptional noise and the changes in cell type composition of the mammalian lung. No robust pattern of cell type-specific transcriptional noise alteration was found across aging lung datasets. In contrast, age-associated changes in cell type composition of the lung were consistently found, particularly of immune cells. These results suggest that claims of increased transcriptional noise of aged tissues should be reformulated.

In Europe and the U.S., proportionately fewer people are developing dementia now than in the past. Is this driven by less-prevalent Alzheimer's disease (AD) pathology? No, say researchers, who reported that among 1,550 older Americans born over a 25-year period, all had similar amounts of amyloid plaques at death, which came at an average of 90 years. If less pathology does not explain falling dementia incidence, then what does? People born in the 1920s had healthier blood vessels in their brains when they died than did those born in the 1900s, the authors found. They think better cardiovascular health among people born in more recent decades may make them more resilient to AD pathology.

Dementia incidence has steadily fallen by 20 to 25 percent over the past three decades in the U.S., U.K., Sweden, and the Netherlands. Researchers suspect that this drop was due to better overall health - especially improvements in cardiovascular health - and higher levels of education . Might these factors stave off amyloid plaques and neurofibrillary tangles? To find out, researchers quantified the extent of amyloid plaques, neurofibrillary tangles, Lewy bodies, TDP-43 aggregates, infarcts, and the severity of atherosclerosis and arteriosclerosis in cortical tissue from 1,554 participants in the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) cohort. About one-quarter were born in each of four periods: 1905 to 1914, 1915 to 1919, 1920 to 1924, and 1925 to 1930. All died between 1997 and 2022.

The prevalence of postmortem AD diagnoses hovered between 64 and 68 percent in each birth epoch. The amount of Lewy bodies and TDP-43 inclusions remained the same across birth cohorts, as well. Notably, people born later had higher densities of neurofibrillary tangles than those born earlier. However, the extent of blood vessel damage, be it through atherosclerosis or arteriosclerosis, had decreased dramatically in participants born in later cohorts. About half of those born from 1905 to 1914 had moderate to severe atherosclerosis, while only 22 percent of people born in later 1920s did. All told, the researchers think that the declining prevalence of clinically diagnosed AD may be due to people having more cognitive reserve, which might be a product of better cardiovascular health and more education.

There are around eight million people living with Parkinson's disease globally; a disease which involves loss of dopamine nerve cells deep in the brain, leading to problems in controlling movement. The standard treatment for Parkinson's disease are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects. As of today, there are no treatments that can repair the damaged structures within the brain or that can replace the nerve cells that are lost.

The STEM-PD trial is now testing a new investigational therapy aimed at replacing the lost dopamine cells with healthy ones manufactured from stem cells. The cell product that is being used has been subjected to rigorous pre-clinical tests. After being transplanted, the cells are expected to mature into new and healthy dopamine producing nerve cells within the brain. On 13th of February 2023, a transplant of stem cell-derived nerve cells was administered to a person with Parkinson's. The product is being tested in patients for the first time. The transplantation product is generated from embryonic stem cells and functions to replace the dopamine nerve cells which are lost in the parkinsonian brain.

This patient was the first of eight with Parkinson's disease who will receive the transplant. The patients in the trial were diagnosed with Parkinson's at least ten years ago and are at a moderate stage of their disease. The researchers will follow these patients closely and assessments of cell survival and potential effects will be conducted over the coming years.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs.

Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry, and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.

In recent decades, the concept of extracellular vesicles (EVs) has changed. When they were initially discovered, EVs were cellular dust; therefore, they did not have any functions; with time, this concept has changed and will probably continue being updated. Nowadays, EVs are considered critical mediators in physiological and pathophysiological processes. Therefore, this review summarizes the current knowledge on EVs from their discovery as cellular dust to their recognition as "very important particles" (VIPs) that mediate cell-cell communication and the current and newest isolation methods. Moreover, we describe the role of EVs in aging and age-related diseases and their potential use in the clinic as biomarkers for early diagnosis and as therapeutic agents for disease treatment.

EVs display several features that provide them with invaluable abilities for their application in regenerative medicine. First, the EV content mimics their parental cells. Thus, isolation of EVs from body fluids with a specific cargo is very useful as a biomarker in disease development for early diagnosis. Second, EVs have a specific set of surface proteins that indicates their target cells. This characteristic also has a valuable potential for their use as drug-delivery carriers to target cells. To date, EVs are VIPs because they act as mediators in physiological and pathological processes. Particularly, as shown in this review, EVs mediate biological aging and premature aging by their content and number released by senescent cells.

Research is still needed in the EV therapeutic field, in particular, focusing on the development of autologous EVs that would enable personalized treatment for each specific disease. Regarding the research on EV-mediated mechanisms of aging, efforts should be performed to establish a time- and cargo-dependent correlation between EVs and the incidence of age-related diseases so that EVs become a very early biomarker. It is also necessary to elucidate the exact molecular mechanisms involved in the change in EV content during aging; this understanding would help us to develop new cell-free treatments to reverse age-related diseases in the future. However, it should be mentioned that before starting antiaging therapies with EVs, safety, sensitivity, and specificity must be precisely verified. Additionally, administration, dosages, treatment intervals, and duration must be strictly certified.

Recent progress in the field of targeted protein degradation (TPD) has proven its immense potential as a novel therapeutic modality in drug discovery. In 2015, researchers devised a phthalimide-based small molecule that promotes degradation of transcriptional coactivator BRD4 by hijacking the Cereblon (CRBN) E3 ubiquitin ligase complex. In the same year, others also reported a TPD technology recruiting the von Hippel-Lindau (VHL) E3 ligase complex, commonly referred to as proteolysis-targeting chimeras (PROTACs). These technologies feature bifunctional small molecules that bring the proteins of interest into proximity with the E3 ubiquitin ligase complexes for ubiquitination and subsequent proteasomal degradation.

Such TPD-based small molecules have several advantages over traditional small molecule inhibitors in that they eliminate the target protein instead of modulating its function. TPD technology thus can complement nucleic acid-based gene knockdown in removing unwanted intracellular proteins. In addition, the TPD technique can target a plethora of proteins in various compartments of the cell, including disease-causing proteins that have previously been considered undruggable with the conventional small-molecule approach. Recently, several strategies have been suggested to potentiate therapeutic efficacy of TPD technology. In particular, TPD molecules that recognize and bind to the protein with specific post-translational modifications (PTMs), such as phosphorylation, may be a novel strategy to induce selective degradation of pathological proteins attributed to aberrant PTMs. However, a TPD molecule specifically targeting post-translationally modified proteins has not been reported yet.

It has been reported that phosphorylated p38 (p-p38) is significantly upregulated under pathological conditions, such as chronic inflammation, thus triggering downstream signal transduction and leading to pathological deterioration. P38 dysfunction has been implicated in a variety of medical disorders, such as neuroinflammation, ischemia, and cognitive impairment. Our previous study showed that enzymatic inhibition of p38 alleviated pathological symptoms of Alzheimer′s disease (AD), particularly neuroinflammation and accumulation of beta-amyloid (Aβ) and tau proteins. The therapeutic potential of inhibiting p38 in neurodegeneration has been investigated in several clinical trials, but there has been no success yet partly due to off-target effects and insufficient efficacy.

In this study, we use targeted protein degradation as a strategy to induce selective degradation of p-p38. Based on the phosphorylation-dependent conformational difference in p38, we rationally designed and synthesized a series of p-p38-degrading small molecules, consisting of a p-p38 ligand and pomalidomide that can recruit the CRBN E3 ubiquitin ligase complex. We found that one candidate molecule induced selective in vivo degradation of p-p38 and ameliorated neurodegenerative symptoms including neuroinflammation, Aβ deposition, and memory loss. Overall, this study highlights selective targeting of p38 bearing a specific PTM for proteasomal degradation, providing a novel therapeutic approach for the treatment of AD.

Our lead drug candidate is a cyclodextrin that targets an oxidized cholesterol called 7-ketocholesterol that accumulates in various cells and tissues with age, and the main type of tissue that we are looking at is in the artery where, as I'm sure everyone knows, cholesterol is considered the bad guy that accumulates and causes plaque, the buildup inside of your arteries. What a lot of people don't know is that the most toxic and the most atherogenic is the oxidized cholesterol form. Atherosclerosis is the buildup of plaque inside of your arteries, which is formed by the accumulation of this oxidized cholesterol form. Additionally, unlike cholesterol, which you absolutely need to survive, you don't need any of this oxidized form. And so that's our target. Our lead drug candidate can go into cells and tissues and even penetrate plaque and grab onto that oxidized cholesterol, pull it out and then float away with it, so you can safely excrete it.

We studied all the cyclodextrins in the chemical catalog, and then we did all this computational modeling, and we figured out that the best way to grab onto our target was to dimerize it to basically take two cyclodextrin molecules, stick them together in the right configuration, and then modify it chemically in particular ways to give it the right shape in the binding cavity. Then what it does is, it grabs it and then it eats a single molecule of its target, a bit like Pac-Man, then wraps around it, and the inside cavity forms a shape around the target that fits it. It can then bind it with extremely high affinity and specificity and float away with the 7-ketocholesterol.

We're well into the process of preparing for clinical trials. We've brought on board a noted expert in developing cardiovascular drugs, and are building a team to plan, initiate, and run the clinical trials. Importantly, this is going to start in months, not years. We're going to start clinical trials in 2023, and.we're well along the path of getting ready for that. There's a certain number of things that you need to do with a drug candidate to be ready for that, and you can put them into two basic categories. First is safety testing your drug and the other is in the manufacturing process, and so we're in the final stages of doing the safety testing. Then we need to manufacture the actual version of the drug that will go into people. We're making several kilograms of the final drug product right now, and that's already begun. Then, all the data on both the manufacturing of the drug and the safety testing will be submitted to the regulatory body, at which point we ask for permission to initiate clinical trials.

Extracellular vesicles (EVs) are membrane-enclosed particles secreted by cells and circulating in body fluids. Initially considered as a tool to dispose of unnecessary material, they are now considered an additional method to transmit cell signals. EV alteration with aging suggests that the modulation of EV release, in terms of number and content, could represent a target to slow aging and for the therapy of age-related diseases.

First, the evaluation of EV features associated with aging (i.e., number, size, specific markers, genetic and/or biochemical content) could represent a possible biomarker of aging, useful to evaluate a variety of age-delaying therapeutic approaches. Second, the decrease of EVs number, via the removal of senescent cells which are known to release a higher number of EVs, could represent a rejuvenating tool associated with treatment with senolytic drugs. Third, the administration of EVs including key components showing anti-aging effects could be an effective rejuvenating strategy, potentially safer than the administration of whole cells.

Nonetheless, these studies are still preliminary and key issues have still to be elucidated. These challenges require further studies assessing the specific content of aging-associated EVs, as well as the development of methods and tools to produce EVs containing rejuvenating factors in a safe and abundant manner. In cell models, there is agreement that cell senescence is associated with an increased release of EVs, but the functional role of these EVs is less clear, as a few studies have reported pro-senescent and pro-apoptotic effects, whereas others have described a pro-tumorigenic role.

As for body fluid EVs, further studies are needed to assess whether aging is associated with an increased or decreased number of EVs, and the main biochemical features of EVs circulating in old versus young individuals, both in humans and in animal models, need to be further elucidated. Indeed, it must be considered that these samples are subjected to mechanical, chemical, and thermal stress during sampling and processing. This may notably change the shape, size, and composition of EVs in a manner that could be possibly influenced by age-related factors. However, there is converging evidence that EVs from young subjects have a rejuvenating effect and vice versa.

Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed.

We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation.

The thymus gland is a small organ tucked beneath the breastbone. Its primary function is to produce T cells, which help the body ward off infections and diseases and mount an immune response to vaccines. The thymus grows weaker with age and is less capable of producing naïve T cells, leading to immune dysfunction and various chronic conditions.

Thymmune Therapeutics debuted recently with 7 million in seed financing. Thymmune aims to reverse thymic atrophy by combining machine learning with cellular engineering to mass produce thymic cells derived from induced pluripotent stem cells. With this approach, the start-up intends to create off-the-shelf cell therapies that can restore immune function minimally invasively.

The small team will first test their platform against athymia, a rare and congenital immune disorder wherein an infant is born without a thymus. Babies with athymia cannot produce T cells and are at a high risk of infection. Left untreated, athymic infants typically die by age two or three. The company is also looking at testing its platform to treat several autoimmune diseases and address organ transplant tolerance. In the future, Thymmune's platform could also boost immune function and address the biology of aging.