In this newsletter, we're going to take a look at all the longevity biotech companies that are developing therapies that target mitochondrial dysfunction - one of the "Hallmarks of Aging". Mitochondria companies make up one of the biggest subcategories in longevity biotech. This makes sense as mitochondria are an extremely critical component of our cells. There are ~20+ longevity mitochondria companies currently, ranging from early stage-startups to Nasdaq-listed public companies. From small molecule drugs to gene therapies and mitochondrial transfusions. Seven of the companies are in clinical trials today.

Aging is not an accepted clinical indication (yet). So the current playbook for longevity biotech companies is to target a disease that shares the same underlying cause as one of the hallmarks/targets of aging for their first clinical trials and expand from there. Usually, this means an age-related disease or a rare genetic disease. Mitochondrial dysfunction is implicated in many diseases of aging. Longevity companies that target mitochondrial dysfunction generally choose clinical indications such as: mitochondrial diseases caused by mitochondrial DNA mutation or nuclear DNA mutations (LHON, Pearson syndrome, etc), muscle dystrophy diseases or muscle loss (Duchenne muscular dystrophy, Becker muscular dystrophy, sarcopenia), metabolic disorders (NASH, Obesity, NAFLD, Type 2 Diabetes), neurodegenerative disease (Alzheimer's, Parkinson's, etc), or conditions linked to oxidative damage (ischemia-reperfusion injury).

Mitochondria are complex. It's still an open question on how they drive aging. Hallmarks of Mitochondrial Aging? Mitochondria have their own DNA, membranes, ribosome, move around (sometimes outside of the cell!), undergo fission and fusion, and provide one of the most critical cellular functions. Since they are almost like their own organism they probably deserve their own "Hallmarks of (Mitochondria) Aging" paper. But just like the original Hallmarks paper, it will be filled with many correlations and questions while causation is not always clear.

Mitochondrial transfer is very promising. I'll admit I am biased towards replacement therapies for anti-aging when it makes sense. It's a clean philosophical approach that lends itself to engineering more than traditional drug development. And unlike stem cell therapies or cellular transplants mitochondria can be replaced easily without the need for extracellular scaffolding or any kind of extra in situ differentiation. There will likely be a number of challenges to work out, though (sourcing allogeneic mitochondria, systemic distribution, determining long-term side effects, etc). One caveat: It is possible that transplanting healthy mitochondria into an old and dysfunctional cellular environment will quickly impair the transplanted organelles. Also, we need to consider the microtubules mitochondria use to move around the cell.

Protect mitochondrial DNA or remove mutations? GenSight Biologics is definitely one of the most interesting biotech companies I have ever stumbled upon. And while their therapies aren't considered anti-aging at the moment (save for GS020 for dry AMD), the technology is a step towards possibly solving the problem of mitochondrial mutations. But even here it is not clear whether it is more important to protect mitochondrial DNA from new mutations or stop already mutated mitochondrial DNA from accumulating via clonal expansion (like Shift Bioscience). Some researchers have also proposed using various DNA editing techniques (TALENS, Zinc Finger Nuclease, CRISPR) to destroy mutant mitochondrial DNA.

A recent study analysed data from the Human Mortality Database (HMD), specifically looking at the probability of death at a given age. For various countries, including the US, Sweden, and Japan, individuals over 50 years had their mortality postponed, on average, by a decade for every age group (50s, 60s, 70s, etc.) from 1967 to 2017. In the example of Sweden, mortality remained constant more or less over the 19th and 20th centuries, until 1950 where an international life expectancy revolution took place.

This could be due to the colossal medical advancements that took place: the discovery of the structure of DNA, novel vaccines, the first successful kidney transplant, a novel antibiotic tetracycline, the first oral contraceptive and the invention of the internal pacemaker. Since then, life expectancy increased almost linearly at a rate of 2.5 years per decade all over the world. This same trend is observed in the longevity leader - Japan. Undoubtedly, the improvements in mortality stem from postponing it and thus prolonging both lifespan and healthspan. People are living longer due to being healthier and thus aging diseases are pushed back, developing later in life.

There are three predominant views on which longevity researchers speculate about the future of life expectancy: 1) life expectancy will rise, but more slowly that in the past due to reaching the 'limit'; 2) the same 2.5 year per decade increase in life expectancy will continue as in the past; 3) life expectancy will rise at a much faster rate due to biomedical advances, as previously seen in the 1950s. The future for longevity will differ from the past, as various mortality improvements play their part. A more effective public health strategy, along with devising treatments to cure aging diseases, such as dementia and cancer, would push out the current limits of healthspan and lifespan. Furthermore, developments in precision medicine, nanotechnology, regenerating tissues, and research on the biology of aging may all lead to slowing rates of aging.

Researchers have in the past provided evidence to suggest that shelterins, proteins that wrap around telomeres and act as a protective shield, might be therapeutic targets for cancer treatment. Subsequently, they found that eliminating one of these shelterins, TRF1, blocks the initiation and progression of lung cancer and glioblastoma in mouse models and prevents glioblastoma stem cells from forming secondary tumours. Now researchers go one step further and describe for the first time how telomeres can be regulated by signals outside the cell that induce cell proliferation and have been implicated in cancer. The finding opens the door to new therapeutic possibilities targeting telomeres to help treat cancer.

Researchers have outlined a link between TRF1 and the PI3K/AKT signalling pathway. This metabolic pathway, which also encompasses mTOR, is one of the pathways most frequently affected in numerous tumorigenic processes. However, it was not known whether preventing TRF1 regulation by this pathway can have an impact on telomere length and its ability to form tumours. AKT acts as a transmitter of extracellular signals triggered by, among others, nutrients, growth factors, and immune regulators, to the interior of cells.

Researchers modified the TRF1 protein in cells to make it unresponsive to AKT, using the gene-editing tool CRISPR/Cas9. This way, TRF1 and the telomeres became invisible to any extracellular signals transmitted by AKT. Telomeres in these cells shortened and accumulated more damage; most importantly, the cells were no longer able to form tumours, indicating that telomeres are important targets of AKT and its role in cancer development.

The paper shows that telomeres are among the most important intracellular targets of the AKT pathway to form tumours, since, although neither the function of AKT nor of any of the thousands of proteins that are regulated by it was altered, only blocking AKT's ability to modify telomeres was sufficient to slow tumour growth. The next step will be to generate genetically modified mice with telomeres that are invisible to AKT. The authors anticipate that these mice will be more resistant to cancer.

The telomere-bound shelterin complex is essential for chromosome-end protection and genomic stability. Little is known on the regulation of shelterin components by extracellular signals including developmental and environmental cues. Here, we show that human TRF1 is subjected to AKT-dependent regulation. To study the importance of this modification in vivo, we generate knock-in human cell lines carrying non-phosphorylatable mutants of the AKT-dependent TRF1 phosphorylation sites by CRISPR-Cas9.

We find that TRF1 mutant cells show decreased TRF1 binding to telomeres and increased global and telomeric DNA damage. Human cells carrying non-phosphorylatable mutant TRF1 alleles show accelerated telomere shortening, demonstrating that AKT-dependent TRF1 phosphorylation regulates telomere maintenance in vivo. TRF1 mutant cells show an impaired response to proliferative extracellular signals as well as a decreased tumorigenesis potential. These findings indicate that telomere protection and telomere length can be regulated by extracellular signals upstream of PI3K/AKT activation, such as growth factors, nutrients, or immune regulators, and this has an impact on tumorigenesis potential.

In an earlier article, we presented the evidence that growth hormone (GH) has an important role in the control of aging and longevity. Much of the evidence for this role of GH was derived from studies of mice with spontaneous or experimentally induced mutations affecting the somatotropic axis and transgenic mice with chronic increase in circulating GH levels. Results of these studies indicated that (i) major elevation of GH levels accelerates aging and shortens life; (ii) stimulatory actions of normal (physiological) GH levels on growth, maturation, and fecundity involve costs in terms of the rate of aging and average as well as maximal longevity; and (iii) suppression of GH signaling slows the process of aging, increases healthspan, and remarkably extends longevity at the expense of reduced growth, delayed puberty, diminutive adult body size, and reduced fecundity. Importantly, these effects of GH on aging as well as the associated trade-offs were shown to apply to normal mice (animals without genetic modifications) and to other mammalian species.

In humans, familial longevity is associated with reduced GH secretion, and height, a strongly GH-dependent trait, is negatively correlated with longevity in many (although not all) of the examined populations. Hereditary conditions of isolated GH deficiency (IGHD) or GH resistance do not extend human longevity, but appear to extend healthspan and provide strong, and in some cases complete, protection from age-associated diseases. Pathological elevation of GH levels in the syndrome of acromegaly reduces both healthspan and life expectancy, likely reflecting acceleration of the aging process.

Paradoxically, recombinant GH treatment of middle aged or elderly subjects, in whom secretion of GH is naturally reduced, can have beneficial effects on body composition along with subjective improvement in various aspects of the quality of life. Beneficial effects of insulin-like growth factor I (IGF-I), a key mediator of GH actions on various aging-associated traits, support the notion that GH can act as an anti-aging agent. However, age is not among the approved indications for GH therapy and side effects and risks of GH therapy are generally believed to outweigh known or hoped-for benefits.

Available evidence indicates that most of the aging-related effects of GH which were discovered in laboratory mice apply to other mammals, including humans, but important species differences also exist. We speculate that differences in the impact of GH on longevity in mice versus people stem from major differences in life history, energy partitioning, and reproductive strategy between species with a different pace-of-life. The slow pace-of-life of humans combined with the impacts of social organization, public health measures, and medical advances, favors longevity and makes it difficult to induce further increase in lifespan.

The risk of both neurodegenerative disease and cancer increases with advanced age due to increased damage accumulation and decreased repair capabilities; yet the relative odds of developing one or the other are inversely correlated. Molecular profiling studies have identified disrupted genes, proteins, and signaling pathways shared by neurodegenerative diseases and cancer, but in opposing directions. For example, p53 is upregulated in Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease, but downregulated in many cancers. Similarly, mutations of the Parkin gene (PARK2) have been shown to simultaneously contribute both to Parkinson's disease and tumor suppression. A recent study performed transcriptomic analyses of four different tissues from four different species at ages across their lifespan. Across samples, the largest number of shared risk single nucleotide polymorphisms (SNPs) were in the genomic locus containing the long non-coding RNA ANRIL which modulates many cell cycle regulators including CDKN2A/B, which codes for p16INK4A (hereon referred to as p16), one of the best characterized mediators of cellular senescence. Notably, SNPs in this locus were identified in the brain, as well as other tissues analyzed. These results point toward aberrant cell cycle, and in particular senescence, as a key age-associated molecular pathway worth further study.

Cellular senescence has emerged as a hallmark biological process that promotes aging. The pillars of aging, including cellular senescence, are highly interconnected and do not occur in isolation. For example, epigenetic changes, telomere attrition, DNA damage, and mitochondrial dysfunction all may induce cellular senescence, which then contributes to dysfunctional nutrient signaling and proteostasis. Consequences of cellular senescence include stem cell exhaustion and chronic inflammation. Thus, cellular senescence represents an intersection of aging hallmarks. While best studied as an anti-cancer stress response, recent studies highlight its pro-degenerative role in AD and tauopathies. As such, cellular senescence may contribute to the inverse correlation between the risk for developing neurodegeneration and that for cancer.

Bulk tissue analyses, while informative at a macroscopic level, may not capture important changes occurring in single cells. Senescent cell abundance increases with aging, but the relative contribution to a tissue is relatively low and may be missed in bulk analyses. Several laboratories are using single cell technologies to assign cell type specificity to tissue-level observations, but to date these analyses have not included senescent cells in the brain. To maximize generalization and interpretation across studies, in this review we only evaluate studies which investigated cellular senescence with cell type specificity, and not bulk analyses. The present compilation provides evidence on conditions in which cellular senescence may benefit (anti-cancer) or negatively impact (neurodegeneration) brain health. In doing so, this review explores how the cellular senescence stress response may simultaneously distinguish and connect AD and cancer risk.

What constitutes a good diet remains a matter of continuous debate. The typical way of addressing such questions in a laboratory setting would be to compare groups given diets with different macronutrient compositions and measure their lifespans. But in real life, food is neither presented nor consumed that way. First, foods vary in their composition of macronutrients. Second, all creatures tend to have innate preferences towards certain foods. Taking these discrepancies into account, would we see a connection between macronutrients and longevity in a more naturalistic, choice-based food environment?

Researchers set out to address this topic in a widely used model system, the fruit fly Drosophila melanogaster. In the first set of experiments, one group of wild-type fruit flies spent their lives on a diet consisting of equal amounts of sugar and protein (fixed diet). The second group received the same amount and ratio of sugar and protein, but they could choose between the two foods (choice diet). Then, the amount of food consumed and lifespans were measured and compared across both groups. Alas - and perhaps unsurprisingly - flies given the choice between sugar and protein consumed far more sugar and lived less long than those given no choice in the matter.

However, the reduced longevity of the 'sweet-toothed' flies could not be attributed solely to sugar-induced toxicity. Even flies given up to three times as much sugar as protein in the fixed-diet group had an intermediate lifespan. Additionally, other measures, such as intestinal permeability and locomotion, were unaltered by the choice diet, at least in young flies. Not even a major messenger molecule in the insulin signaling pathway (dFOXO), a key culprit in diet-induced longevity, was greatly affected by a choice-driven diet. Instead, it appeared that being presented with the choice itself led to increased sugar consumption and reduced longevity.

Researchers were able to show that a serotonin receptor called 5HT2A was responsible for the choice-induced reduction in lifespan. However, when 5HT2A was removed, flies on a choice diet no longer had shortened lifespans, even though they consumed just as much sugar as the wild-type flies. Researchers suspected that variations in internal nutrients could be behind the observed changes in lifespan. They compared a large number of metabolites relevant for converting food to energy in flies raised on both diets, and with or without 5HT2A. Over 80% of these metabolites did not change. However, in flies raised on a choice-diet, four amino acids (lysine, glutamine, asparagine, and aspartate) increased in a 5HT2A-dependent manner.

Researchers have identified a potential new marker that shows cardiovascular disease may be present in a patient using an optical coherence tomography (OCT) scan - a non-invasive diagnostic tool commonly used in ophthalmology and optometry clinics to create images of the retina. The finding suggests it may be possible to detect heart disease during an eye examination. The research team examined lesions of the retina, the inner-most, light-sensitive layer of the eye, to determine if a cardiovascular disorder may be present.

"The eyes are a window into our health, and many diseases can manifest in the eye; cardiovascular disease is no exception. Ischemia, which is decreased blood flow caused by heart disease, can lead to inadequate blood flow to the eye and may cause cells in the retina to die, leaving behind a permanent mark. We termed this mark 'retinal ischemic perivascular lesions,' or RIPLs, and sought to determine if this finding could serve as a biomarker for cardiovascular disease."

As part of the study, the team reviewed the records of individuals who received a retinal OCT scan. From that cohort, two groups were identified after medical chart review: one consisted of 84 individuals with heart disease and the other included 76 healthy individuals as the study's control group. An increased number of RIPLs was observed in the eyes of individuals with heart disease. According to the researchers, the higher number of RIPLs in the eye, the higher the risk for cardiovascular disease. Detection of RIPLs could result in identification of cardiovascular disease that would enable early therapy and preventative measures, and potentially reduce numbers of heart attacks or strokes.

Antibodies are an important component of the immune system. On the one hand, these proteins serve in the body to defend against microbes, and on the other hand to remove the body's own "cell waste". Naturally occurring antibodies which are present from birth and mostly of the immunoglobulin-M (IgM) type, play an essential role in these processes. In the context of thrombosis, earlier studies demonstrated that people with a low number of IgM antibodies have an increased risk of thrombosis. Thrombotic occlusion of blood vessels, which leads to myocardial infarctions, strokes, and venous thromboembolisms, is the major cause of death in the western hemisphere. Therefore, it is of critical importance to understand the mechanisms that might prevent thrombus formation.

Microvesicles, blebs shed from the membrane of cells, are critical mediators of blood coagulation and thrombus formation. Researchers have now demonstrated that natural IgM antibodies that bind oxidation-specific epitopes can prevent coagulation and thrombosis induced by microvesicles. This provides a mechanistic explanation for the previously published observation that low levels of these antibodies are associated with an increased risk of thrombosis. Both in experiments on a mouse model and directly on human blood samples, the scientists were able to show that the addition of IgM antibodies inhibited blood clotting caused by specific microvesicles and protected mice from lung thrombosis. Conversely, it was also shown that depletion of the IgM antibodies increased blood clotting.

"The results offer high potential for novel treatments to reduce the risk of thrombosis. Influencing IgM antibody levels in high-risk patients could be a viable addition to the previously established blood thinning treatment, as this is also known to be associated with side effects such as an increased tendency to bleed in the case of injuries."

In recent years, many experts in the aging field have come to believe that certain medications acting at the cellular and metabolic level can slow aging by staving off its most striking effects - frailty and ­age-related diseases, for example - and extend healthy life in doing so. Now they are setting out to prove it. "We're not about the fountain of youth," says Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine. "That's taking an old person and making him young. What we are saying is that we can delay aging."

Drugs with the ability to postpone or prevent the onset of debilitating diseases could lead to additional healthier years, enhancing longevity and providing enormous societal benefits, experts say. Leading the list of candidates is metformin, a longtime treatment for type 2 diabetes, and rapamycin, a chemotherapy agent and immunosuppressant. Scientists also are studying a class of compounds known as senolytics, which attack "senescent" cells in the body that tend to proliferate with age. Senescent cells damage healthy cells around them, contributing to multiple age-related diseases.

But such drugs could face a daunting challenge, since aging is not considered a disease. This means the Food and Drug Administration is unlikely to approve a drug for its anti-aging effects, or as a new use for a licensed drug. Also, pharmaceutical companies probably wouldn't be inclined to develop drugs for that purpose only. Scientists hope to circumvent that hurdle by conducting a study - in this case, with metformin - to test whether it can prevent or delay three age-related diseases - dementia, heart disease and cancer - and, in doing so, extend life.

At least one study had heightened their interest in the drug as possibly life-extending after researchers noticed that diabetics who took the drug outlived non-diabetics who did not. Moreover, metformin had shown an effect in separate studies against each of the three diseases, prompting the researchers to try to put all the pieces together in one large randomized controlled clinical trial. The result is a proposed six-year clinical trial, known as Targeting Aging With Metformin (TAME), which will recruit 3,000 subjects ages 65 to 79 at 14 research sites. In testing whether metformin can prevent or delay the three diseases, researchers also hope to learn whether this results in those taking metformin outliving those not taking the drug, thus extending healthy life. (One reason for choosing metformin was because of its long track record, safety, and inexpensive cost.)

"The goal is not to help people live forever, but help them stay healthy longer," says Steven Austad, who chairs the biology department at the University of Alabama at Birmingham and is senior scientific director of the American Federation for Aging Research. "But the fringe benefit is that you live longer."

Amyloid beta (Ab) proteins are the primary driver of Alzheimer's disease but also begin to collect in the retina as people get older. Donor eyes from patients who suffered from age-related macular degeneration (AMD), the most common cause of blindness amongst adults in the UK, have been shown to contain high levels of Ab in their retinas.

A new study builds on previous research which shows that Ab collects around a cell layer called the retinal pigment epithelium (RPE), to establish what damage these toxic proteins cause RPE cells. The research team exposed RPE cells of normal mouse eyes and in culture to Ab. The mouse model enabled the team to look at the effect the protein has in living eye tissue, using non-invasive imaging techniques that are used in ophthalmology clinics. Their findings showed that the mouse eyes developed retinal pathology that was strikingly similar to AMD in humans.

The investigators also used the cell models, which further reduced the use of mice in these experiments, to show that the toxic Ab proteins entered RPE cells and rapidly collected in lysosomes, the waste disposal system for the cells. Whilst the cells performed their usual function of increasing enzymes within lysosomes to break down this unwanted cargo, the study found that around 85% of Ab still remained within lysosomes, meaning that over time the toxic molecules would continue to accumulate inside RPE cells. Furthermore, the researchers discovered that once lysosomes had been invaded by Ab, around 20 percent fewer lysosomes were available to breakdown photoreceptor outer segments, a role they routinely perform as part of the daily visual cycle.

We estimate a stochastic life-cycle model of endogenous health spending, asset accumulation, and retirement to investigate the causes behind the increase in health spending and longevity in the United States over the period 1965-2005. Accounting for changes over time in taxes, transfers, Social Security, income, health insurance, smoking and obesity, and technological progress, we estimate that technological progress is responsible for half of the increase in life expectancy over the period.

Substantial growth in health spending over the period is largely the result of growth in economic resources and the generosity of health insurance, with a modest role for medical technological progress. The growth in spending does not come from changes in a single source, but sources jointly interacted to increase spending: complementarity effects explain up to 26.3% of the increase in health spending. Overall, for those born in 1940, the combined changes in resources and health insurance that occurred over the period are valued at 35.7% of lifetime consumption.

Death and aging constitute a mystery. Some of us die more quickly. We often ask about it as children, deny it in youth, and reluctantly come to accept it as adults. Aging is universal across all species. In the bare-fact of our aging and dying, we resemble all other animals; in the details, however, we've improved considerably over the course of our history. At some point, our bodies decide to grow senescent and then to die. It's intrinsic, initiated from within the organism. The repeated shuffling of sirtuins and other epigenetic factors away from genes to sites of broken DNA, then back again (while helpful in the short term) is ultimately what causes us to age. Over time the wrong genes come on at the wrong time and in the wrong place. When you disrupt the epigenome by dealing with DNA breaks, it results in an erosion of the epigenetic landscape of misguided and malfunctioning cells.

A malady that impacts less than half the population is a 'disease'. Aging impacts everyone and therefore is an inevitable, irreversible decline in organ function that occurs over time even in the absence of injury, illness, environmental risks, or poor lifestyle choices. Aging limits the quality of life and has a specific pathology. It does all this and in doing so it fulfills every category of what we call a 'disease', except one; it impacts more than half of the population. It's the mother of all diseases, the one we all suffer from. Aging, by all means, is a disease though not yet considered so by any country. Insurance companies don't cover pharmaceuticals to treat cases that aren't recognized by government regulators even if it benefits humanity and the nation's bottom line. Without such a designation, unless you're suffering from a specific disease, longevity drugs will have to be paid for out of pockets, for they'll be elective luxuries.

As nobody has been working on any cure, because what's wrong with oldies isn't viewed as an illness. It's thought to be an inevitable part of life. Cancer, heart diseases, Alzheimer's, and other conditions we commonly associate with getting old aren't necessarily diseases themselves but symptoms of something greater. Efforts to define aging as a 'disease' both in custom and on paper will change the course of the future. Besides public funding to augment the cure doctors will feel comfortable prescribing medicines, such as Metformin, to their patients before they become irreversibly frail. Jobs will be created and scientists and drug makers will flock, industries will flourish.

There's a difference between extending life and prolonging vitality. We're capable of both but simply keeping people alive is no virtue. Life-extension means the recovery of the physical/intellectual capital that's tied up in hospitals and clinics, treating sick oldies. Add to this the billions of additional women, if provided, much longer windows of opportunity for pregnancy and parenting and extended female fertility by up to a decade or so. Imagine the combined intellectual power of the men and women who're currently sidelined due to age-discrimination, socially enforced ideas about the right time to retire, and diseases that rob them of the physical and intellectual capacity to engage, as they once did.

Creating 200 billion-plus brand-new red blood cells a day can take a toll on a body. The capacity to replace components charged with the life-sustaining task of carrying oxygen eventually wears out with aging, resulting in health problems, from anemia to blood cancers. What if we could halt the aging process and maintain young blood cells for life? With blood cells making up a whopping 90% of the body's cells, it makes sense that keeping them abundant and fit could boost vitality into our golden years.

Blood cells are responsible for oxygen transport, infection control, and many other things scientists are just discovering. But they have a short lifespan - 120 days for red blood cells, and even shorter for other blood cells - and must regenerate continuously throughout life, he said. "This fascinating phenomenon is made possible by the capacity of hematopoietic stem cells (HSCs) to multiply and differentiate into all the blood cell types, a mechanism that unfortunately can become impaired as we get old. Results can include anemia, when we can't make enough red blood cells, or blood cancers, when some blood cell precursors go rogue and start multiplying without differentiating,"

The researchers targeted chaperone-mediated autophagy (CMA), one mechanism they found responsible for the degradation. Like a housekeeper gone awry, CMA with age can fail in its job of cleaning up damaged proteins and other wastes, sabotaging the HSCs' capacity to make new, healthy blood cells. Pinpointing one key protein (LAMP2A) that regulates CMA function whose expression and activity declines with age, the scientists used both genetic, dietary and pharmacological interventions that restored young hematopoiesis (formation of blood cellular components) in old laboratory mice.

The scientists also showed that a metabolic enzyme (FADS2) involved in fatty acid metabolism loses function with age, reducing healthy blood cell formation. By introducing gamma linolenic acid (GLA), a product of the failing enzyme, in the rodents' diets, the researchers again improved cell regeneration. After determining that the CMA dysfunctions in mice mirrored those in 70-plus-year-old humans, the researchers believe their findings could eventually translate into reversing the aging process of HSCs in humans, opening the door to numerous medical therapies.

Frontier Acquisition Corporation, a special purpose acquisition company formed for the purpose of entering into a combination with one or more biotech businesses, has announced the pricing of its initial public offering of 200 million. Interestingly, the line-up includes Co-Chairmen Peter Attia, a practising physician focusing on the applied science of longevity, and David Sinclair, Professor of Genetics at Harvard Medical School and co-founder of several biotechnology companies.

The new company is headed by German investor Christian Angermayer, founder of Apeiron Investment Group and Chairman and Co-Founder of Cambrian Biopharma. Angermayer laid out his views last year in a detailed post on LinkedIn, where he stated, "Put simply, I want to live forever! And in perfect health! And it is my sincere belief that we will achieve the means to do this within the next 20-30 years."

Angermayer is a serial entrepreneur, backing about 30 life sciences companies, including Atai Life Sciences, Sensei Biotherapeutics, Compass Pathways, and Abcellera. In a statement he said, "I deeply believe biotechnology will be one of the best asset classes to invest in over the next decade. We will see incredible progress that we so far didn't dare to dream about."

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the "stem-less" approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of microRNAs or by modifying the cellular energy metabolism via targeting mitochondria.

Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations.

Despite previous promising usage of mitochondria for transplantations, important considerations regarding the significant aging effects of somatic cells, stem cells, and mitochondria as well as factors like safety issues, tissue sources, and possible disease effects deserve further investigations when mitochondrial transplantations are to be used for future applications. Factors influencing stem cell and mitochondria function include age of the cells, probably previous divisions of the cells, heterogeneity of stem cells as well as mitochondria, and likely tissue source and additional diseases. Furthermore after the first positive reports, the time of treatment for the most beneficial effect and repetitions of applications should be further investigated: positive effects have been shown pre ischemia, prior to and during reperfusion as well as after delayed application.

The quantity of mitochondria seems to be less critical as only a small number of mitochondria is needed for improving cardiac functions. The development of further safety and storage solutions for mitochondria could improve applications. Following the first promising reports of stem cell derived mitochondria further research especially considering the differences of autologous (maybe collection in early life stages and asservation for later use) vs. allogeneic vs. syngeneic sources deserve further investigations and will surely lead to exiting new developments during the upcoming years.