Ageing is one of the main risk-factors for heart failure, as older people are more likely to develop heart disease and don't recover as well following a heart attack. New research explores how senescent cells - also known as zombie cells - form in the heart during ageing and lead to heart failure. Zombie cells occur all over the body as it ages. They get their nickname from the fact that although they are not dead they do not function correctly and can cause other cells around them to become senescent (or zombiefied!) Elsewhere in the body, zombie cells are usually caused by the shortening of structures found at the end of chromosomes called telomeres, which happens progressively each time a cell divides. But as heart cells - cardiomyocytes - rarely divide it was not known if or how these cells could become senescent.

"Previously, it was believed that senescence occurs only as a result of a lifetime of cell division and the shortening of telomeres. Our data support the very exciting idea that heart cells can become senescent due to stress that damages their telomeres rather than the process of division. This mechanism could also explain how other non-dividing cells in our bodies age. We saw that removing senescent cardiomyocytes from the hearts of aged mice, both genetically and using drugs, was able to restore cardiac health - essentially removing the damage caused by ageing. This data provides critical support for the potential of using medicines to kill zombie cells. If this is validated through clinical trials it would provide us with a new way of treating cardiac diseases.

To investigate further the therapeutic impact of targeting senescent cells to counteract cardiac ageing, we treated aged wild-type mice with the previously described senolytic drug, ABT263 (navitoclax) intermittently for 2 weeks. We found that navitoclax reduced telomere dysfunction in cardiomyocytes without affecting telomere length. Similarly, to genetic clearance of p16Ink4a cells in INK-ATTAC mice, we found that navitoclax significantly reduced hypertrophy and fibrosis in aged wild-type mice. However, navitoclax had no significant impact on cardiac function, left ventricle mass and ventricle wall rigidity.

The decrease in mean cardiomyocyte size without significant changes in left ventricle mass suggested a compensatory increase in overall cardiomyocyte number. Supporting de novo cardiomyocyte proliferation, we observed that frequency distribution analyses of cardiomyocyte cross-sectional area suggested that the decrease in mean cardiomyocyte area following navitoclax treatment is a function of both an elimination of the largest cardiomyocytes, presumably as these are senescent, and the appearance of a "new" population of small cardiomyocytes.

Skin injuries activate rapid wound repair, which often culminates with the formation of scars. Unlike normal skin, scars are devoid of hair follicles and fat cells, and creating new hair and fat is necessary for regenerating an equivalent of normal skin. In 2017 researchers identified that adult mice can naturally regenerate nearly normal-looking skin when new hair follicles and fat cells form in healing wounds. New fat cells regenerate from myofibroblasts, a type of wound fibroblast that was previously not thought to be capable of converting into other cell types. This discovery brought renewed attention to wound fibroblasts as attractive targets for anti-scarring therapies. In the current study, the research team sought to further characterize wound fibroblasts and determine if they're all the same and equally capable of regenerating new fat cells.

"We saw that wound fibroblasts are surprisingly very diverse and that there are as many as twelve different cell sub-types. We understand their molecular signatures and are beginning to learn about their unique biology. For example, we already know that distinct fibroblast sub-types 'prefer' only certain parts of the wound. This suggests that they play specific roles in different locations within the wound, and possibly at different times during the repair process. Molecular profiling of wound fibroblasts strongly suggests that as many as 13% of them at some point in their past were blood cells that converted into collagen-producing fibroblasts, but kept residual blood-specific genes still turned on."

"What is truly novel about our observation is that these fibroblast-making blood cells, which are called myeloid cells, can reprogram into new fat cells. In essence, we observed that for wounds to achieve scar-less regeneration, the body must mobilize multiple cellular resources, which includes remotely circulating blood progenitors." Because myeloid cells can be fairly easy to harvest and enrich using existing techniques, the new findings open the exciting possibility that the skin's healing ability can be enhanced via delivery of regeneration-competent blood-derived progenitors to the site of the wound.

Traditionally, adult mammals are considered to have limited regenerative abilities and scarring is thought to be the default repair response. The notable exceptions to this rule are digit tip regeneration after amputation and neogenesis of hair follicles and fat in the center of large excisional wounds. Intriguingly, lineage studies reveal important differences in the regenerative strategies between these two systems. Epithelial and mesenchymal structures in the digit tip regenerate from several types of fate-restricted progenitors and no multipotent progenitors or lineage reprogramming events are observed. In contrast, large skin wounds demonstrate broadened lineage plasticity. Although progeny of preexisting hair-fated bulge stem cells migrate into wound epidermis, they do not partake in hair follicle neogenesis. Instead, new hair follicles regenerate from non-bulge epithelial stem cells, among other sources. Fat neogenesis is driven by lineage reprogramming of non-adipogenic wound myofibroblasts. Dermal papilla neogenesis also likely relies on myofibroblast reprogramming strategy.

Are all wound myofibroblasts identical or heterogeneous in terms of their origin, properties, and morphogenetic competence? Here, we studied fibroblast heterogeneity in the mouse model for wound-induced regeneration at 12 days post-wounding when wound re-epithelialization is completed and preceding hair follicle neogenesis. We show that wound fibroblasts can be broadly classified into two major populations on the basis of their transcription factor signatures and PDGF receptor expression patterns. Prominent additional heterogeneity exists within both populations.

Bone-marrow-derived progenitors, including myeloid cells, endothelial progenitors, and circulating mesenchymal stem cells can contribute new stromal cells toward injured tissues in various organs. In skin, studies document bone marrow giving rise to fibroblasts at the injury sites. Our data from large excisional wounds shows that the contribution from myeloid cells to wound fibroblasts is small yet significant, between 6% and 11.3%, depending on the assessment method. We also showed that at least a portion of these cells can convert into de novo adipocytes around neogenic hair follicles.

For patients with end-stage renal disease, a kidney transplant is the only hope for regaining quality of life. Yet many of these patients will never undergo transplant surgery thanks to a chronic shortage of donor kidneys. But researchers have been working on ways to grow healthy organs outside the human body. One such method, called blastocyst complementation, has already produced promising results. Researchers take blastocysts, the clusters of cells formed several days after egg fertilization, from mutant animals missing specific organs and inject them with stem cells from a normal donor, not necessarily of the same species. The stem cells then differentiate to form the entire missing organ in the resulting animal. The new organ retains the characteristics of the original stem cell donor, and can thus potentially be used in transplantation therapy.

Initial attempts by the researchers to grow rat kidneys in mice proved unsuccessful, as rat stem cells did not readily differentiate into the two main types of cells needed for kidney formation. However, when the reverse scenario was attempted, mouse stem cells efficiently differentiated inside rat blastocysts, forming the basic structures of a kidney. After being implanted into pseudo-pregnant rats, the complemented blastocysts matured into normal fetuses. Remarkably, more than two thirds of the resulting rat neonates contained a pair of kidneys derived from the mouse stem cells. Further screening showed that all of the kidneys were structurally intact, and at least half could potentially produce urine. "Our findings confirm that interspecific blastocyst complementation is a viable method for kidney generation. In the future, this approach could be used to generate human stem cell-derived organs in livestock, potentially extending the lifespan and improving the quality of life of millions of people worldwide."

Regeneration of human kidneys in animal models would help combat the severe shortage of donors in transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation of pluripotent stem cell (PSC)-derived functional pancreas, in apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived kidneys in anephric Sall1 mutant mice, likely due to the poor contribution of rat PSCs to the mouse metanephric mesenchyme, a nephron progenitor.

Here, conversely, we show that mouse PSCs can efficiently differentiate into the metanephric mesenchyme in rat, allowing the generation of mouse PSC-derived kidney in anephric Sall1 mutant rat. Glomerular epithelium and renal tubules in the kidneys are entirely composed of mouse PSC-derived cells expressing key functional markers. Importantly, the ureter-bladder junction is normally formed. This data provides proof-of-principle for interspecific blastocyst complementation as a viable approach for kidney generation.

Statistical data indicate that the mortality rates due to all major age-related diseases increase exponentially with age. Researchers have hypothesized that the reason behind this self-aggravating disease progression is the indefinite repetition of reaction cycles, which increases the harm from the initially noncritical changes in the body manyfold. It is these cycles that prospective therapies might address. "Investigating the mechanisms behind age-related disease progression, one concludes that by the time the disease has been diagnosed, it is too late to address the triggering factors. Apparently the most effective strategy is to interrupt the known vicious cycles by blocking certain stages in them. Drugs doing just that are already being developed."

Researchers examined the mortality rates of patients with five most widespread diseases that tend to affect elderly people more often, leading these diseases to be widely regarded as age-related: atherosclerosis, hypertension, diabetes, Alzheimer's, and Parkinson's diseases. Mortality statistics are the most powerful and least biased tool for studying diseases, since they account for the natural progression of a disease under various life conditions across a large population. A detailed analysis of age-related diseases revealed that they progress exponentially due to reactions on the molecular or cellular level producing pathogenic products which in turn initiate the very reactions that produced them. That way the harmful products quickly multiply, and the disease progresses at an ever increasing rate, like an avalanche.

For example, nerve cells in the brain contain a small amount of a protein called alpha synuclein, which is involved in nerve impulse transmission. It may happen that the gene encoding alpha synuclein is mutated, duplicated, or triplicated in a genome. This leads to multiple protein molecules sticking to one another, forming so-called toxic oligomers, which then grow in size by attaching other alpha synuclein molecules. This process produces fibrils, which from time to time break up into oligomers, each of which eventually grows into a new fibril, etc. This chain reaction causes the number of toxic alpha synuclein oligomers to grow exponentially.

Nationwide mortality and disease incidence statistics are perhaps the most powerful and least biased datasets on human diseases that we currently have. These data are derived from humans living in the complex environment and developing diseases naturally, and not from distantly related animals contained in laboratory conditions under disease-inducing regimens. I decided to use disease statistics to elucidate the underlying nature of five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer's and Parkinson's. As large-scale incidence data for these diseases is not readily available, I have instead evaluated the age distribution of mortality.

It can be seen that the exponential function provides a reasonable approximation for mortality from atherosclerosis, diabetes and Alzheimer's, but is inadequate for mortality from essential hypertension and Parkinson's. The slightly more complex but mathematically correct logistic function provides the fits that are at least as good as for the exponential function, and in addition provides the perfect fit for Parkinson's disease mortality. Finally, the sum of two logistic functions is required for the adequate fit to mortality from essential hypertension. This may indicate that essential hypertension is a heterogeneous disease composed of two major subtypes with different mortality kinetics.

This study showed that potential vicious cycles underlying ARDs are quite diverse and unique, triggered by diverse and unique factors that do not usually progress with age, thus casting doubts on the possibility of discovering the single molecular cause of aging and developing the single anti-aging pill. Rather, each disease appears to require an individual approach. However, it still cannot be excluded that some or all of these cycles are triggered by fundamental processes of aging, such as chronic inflammation or accumulation of senescent cells. Nevertheless, experimental data showing clear cause and effect relationships between fundamental aging processes and ARDs are still missing.

It could also be that the above-mentioned fundamental aging processes themselves are mediated by positive feedback loops. For example, chronic inflammation can amplify itself similarly to autoimmune diseases via cytokines and epitope spreading. Cellular senescence can propagate from cell to cell in a chain-reaction fashion via cytokines and reactive oxygen species. DNA damage may amplify by affecting the genes of more and more DNA repair enzymes. Accumulating intracellular garbage may impair the lysososmal function, leading to ever-accelerating garbage accumulation. However, to test these propositions, longitudinal data on the kinetics of corresponding processes should be obtained.

The world longevity record for Jeanne Calment (122 years) is widely cited with great pride as the gold standard of the highest data quality for many decades. Yet even for this best documented longevity claim, some early doubts were expressed of her suspicious extremely outlying age. Still, most scientists and the public believe in the validity of the Calment longevity record. The situation is even more serious-our studies found that many longevity records for ages 105 years and older are often incorrect (see later). After age 105 years, longevity claims should be considered as extraordinary claims that require extraordinary evidence. Traditional methods of data cleaning and data quality control are just not sufficient. New, more strict methodologies of data quality control need to be developed and tested. Before this happens, all mortality estimates for ages above 105 years should be treated with caution.

Knowledge of true mortality trajectory at extreme old ages is important not only for actuaries but also for biologists who test their theories of aging with demographic data. Studies conducted in the 1990s suggest that the exponential growth of human mortality with age (the Gompertz law) is followed by a period of deceleration, with slower rates of mortality increase. These early studies, as well as studies on insects, convinced researchers of the universality of the mortality deceleration phenomenon, and until recently, there was no doubt among biodemographers and gerontologists that mortality slows down after the age of 80 years. At that time, several biological explanations of mortality deceleration and late-life mortality plateau were suggested. Reliability models of aging also suggest mortality plateau at advanced ages when assuming random loss of functional cells and other essential elements over time.

Recently, the common view about mortality deceleration at advanced ages has been challenged using both theoretical and empirical considerations. It was found that mortality of US extinct cohorts born after 1889 demonstrated the Gompertz-like trajectory in the age interval 85 to 106 years. In the study of old-age mortality in 15 low-mortality countries, Gompertz-like mortality growth was found at older ages for Australia, Canada, and the US and mortality deceleration for other studied countries.

It should be noted that hazard rate estimation at very old ages faces difficulties because of very small number of survivors to these ages, and age misreporting by older persons. Age misreporting is a big problem affecting estimates of mortality at advanced ages. It was found that even a small percentage of inaccurate data can greatly distort mortality trajectories at advanced ages and that age misreporting at older ages results in mortality underestimation. Taking into account that the accuracy of age reporting is positively correlated with education, it is reasonable to expect improvement in age reporting over time and less prevalent mortality underestimation or mortality deceleration at older ages for more recent birth cohorts. Indeed, it was found that late-life mortality in historically older US birth cohorts demonstrates stronger mortality deceleration compared to more recent birth cohorts. These results suggest that mortality deceleration observed in early studies of old-age mortality may be caused by age misreporting at older ages.

Medical care for older adults has long focused on preventing and treating chronic diseases and the conditions that come with them. But now, geriatrics researchers and clinicians hope a new understanding - one honed at a conference hosted by the American Geriatrics Society (AGS) and the National Institute on Aging (NIA) - can lead to better and more effective interventions by targeting the aging process itself rather than discrete conditions or concerns. "Aging is complex and varies from one person to the next, but there's a growing body of evidence that aging itself is driven by interconnected biological factors we call 'hallmarks' or 'pillars'. We believe disrupting these hallmarks - which cover everything from the stability of our genes to ways our cells communicate - can contribute to chronic disease and frailty, which is why a better understanding of how they work is so important."

Rather than beginning with the discrete health conditions and concerns common among older adults, conference organizers took the unique approach of focusing on aging itself as a primary factor impacting multiple chronic diseases and the declining ability to rebound from health challenges (also known as "resilience"). In doing so, scholars advanced our understanding of the concept that targeting age-related mechanisms might delay, prevent, or even reverse geriatric syndromes, age-related chronic diseases, and declines in resilience. Conference sessions also focused on new methods and strategies for studying these aspects of aging, and reviewed the challenges of studying age when older people often have been excluded from medical research.

Retrotransposons are related to ancient retroviruses that, when left unchecked, can produce DNA copies of themselves that can insert in other parts of a cell's genome. Cells have evolved ways to keep these "jumping genes" under wraps, but as the cells age, the retrotransposons can escape this control. A research team has now shown that an important class of retrotransposons, called L1, escaped from cellular control and began to replicate in both senescent human cells - old cells that no longer divide - and old mice. Retrotransposon replication, specifically the DNA copies of L1, is detected by an antiviral immune response, called the interferon response, and ultimately triggers inflammation in neighboring cells.

These retrotransposons are present in every type of tissue, which makes them a compelling suspect for a unified component of cellular aging. Understanding that, the team uncovered the interferon response, the potential mechanism through which these jumping genes may cause cellular inflammation without necessarily causing damage to the genome. The interferon-stimulating copies of L1 DNA require a specific protein called reverse transcriptase. HIV and other retroviruses also require reverse transcriptase proteins to replicate. In fact, AZT, the first drug developed to treat HIV/AIDS, halts HIV reverse transcriptase. Researchers thought that this class of drugs may keep the viral-like L1 retrotransposon from replicating and thereby prevent the inflammatory immune response.

One generic HIV drug, lamivudine, stood out because of its activity and low side effects. Growing human cells in the presence of lamivudine did not impact when the cells reached senescence or kill the senescent cells. But lamivudine did decrease the interferon response and the late-stage senescence-associated secretory phenotype (SASP) - the important characteristics of senescent cells that promote inflammation in their neighbors. "When we started giving this HIV drug to mice, we noticed they had these amazing anti-inflammatory effects. Our explanation is that although L1s are activated relatively late in senescence, the interferon response reinforces the SASP response and is responsible for age-associated inflammation."

Subclinical but heightened inflammation is observed in aging tissues, and in the blood of older adults in large epidemiologic studies, with consistently higher basal levels of C-reactive protein and abundant pro-inflammatory cytokines. Such alteration is often viewed as non-cell autonomous, for example senescent cells, which increase with aging, may modulate inflammation through secretion of cytokines (i.e., senescence-associated secretory phenotype, SASP. The intrinsic processes that initiate this inflammation in aging remain largely unknown.

We previously described a cell-autonomous process in which damaged nuclear DNA is trafficked to the cytosol, transported via autophagy, and degraded by lysosomal nuclease DNASE2A. Excess DNA accumulated under conditions of increased damage, defective degradation, or autophagy blockade can activate the STING pathway leading to inflammation. DNA damage has been postulated to be a major cause of cellular aging. We hypothesize that cumulative damage may generate excess DNA leading to persistent inflammation in aging cells through a similar mechanism. Several observations in senescence seem to agree with our prediction. Unrepaired or persistent double-stranded breaks (DSBs) can be found in senescing cells, and cells are known to senesce upon DNA damage. Senescent nuclei also undergo dramatic chromatin changes with fragments budding off the nucleus.

We found that older cells harbored higher levels of extranuclear DNA compared to younger cells. Extranuclear DNA was exported by a leptomycin B-sensitive process, degraded through the autophagosome-lysosomal pathway and triggered innate immune responses through the DNA-sensing cGAS-STING pathway. Patient cells from the aging diseases ataxia and progeria also displayed extranuclear DNA accumulation. Removing extranuclear DNA in old cells using DNASE2A reduced innate immune responses and senescence-associated β-gal enzyme activity. We hypothesize a direct role for excess DNA in aging-related inflammation and in replicative senescence, and propose DNA degradation as a therapeutic approach to remove intrinsic DNA and revert inflammation associated with aging.

A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer's disease, and brain injuries. A team of researchers identified a set of four, or even three, molecules that could convert glial cells - which normally provide support and insulation for neurons - into new neurons. The team previously published research describing a sequence of nine small molecules that could directly convert human glial cells into neurons, but the large number of molecules and the specific sequence required for reprogramming the glial cells complicated the transition to a clinical treatment.

In the current study, the team tested various numbers and combinations of molecules to identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons. By using four molecules that modulate four critical signaling pathways, they could efficiently turn human astrocytes - as many as 70 percent - into functional neurons. The resulting chemically converted neurons can survive more than seven months in a culture dish in the lab. They form robust neural networks and send chemical and electrical signals to each other, as normal neurons do inside the brain.

The researchers had previously developed a gene therapy technology to convert astrocytes into functional neurons, but due to the excessive cost of gene therapy - which can cost a patient half a million or more - the team has been pursuing more economical approaches to convert glial cells into neurons. The delivery system for gene therapies is also more complex, requiring the injection of viral particles into the human body, whereas the small molecules in the new method can be chemically synthesized and packaged into a pill.

Researchers used state-of-the-art imaging technology to study both mouse brains and human brains from patients with Alzheimer's disease. They also produced the first three-dimensional volume imaging showing that blood-brain barrier leaks occur in Alzheimer's disease. They found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy important connections between neurons. These connections, called synapses, are critical for neurons to communicate with one another.

Previous studies have shown that elimination of synapses causes memory loss, a common feature in Alzheimer's disease and other dementias. Indeed, the scientists showed that preventing fibrinogen from activating the brain's immune cells protected mouse models of Alzheimer's disease from memory loss. "We found that blood leaks in the brain can cause elimination of neuronal connections that are important for memory functions. This could change the way we think about the cause and possible cure of cognitive decline in Alzheimer's disease and other neurological diseases."

The team showed that fibrinogen can have this effect even in brains that lack amyloid plaques, which are the focus of diverse treatment strategies that have failed in large clinical trials. The researchers showed that injecting even extremely small quantities of fibrinogen into a healthy brain caused the same kind of immune cell activation and loss of synapses they saw in Alzheimer's disease. Interestingly, researchers recently developed an antibody that blocks the interaction between fibrinogen and a molecule on the brain's immune cells. In a previous study, they showed this antibody protected mouse models of Alzheimer's disease from brain inflammation and neuronal damage.

Maximum lifespan (MLSP) is a species-specific feature that may differ more than 5000-fold among animal species being about 120 years in humans. Centenarians are considered an exceptional human model of healthy aging and extreme longevity. Available evidences reveal the existence of a link between MLSP and lipids. Thus, the findings from several studies demonstrate that the membrane fatty acid profile differs between animal species (including vertebrates, invertebrates, and exceptionally long-lived animal species) and that cell membrane susceptibility to lipid peroxidation is inversely related to MLSP. Furthermore, a recent phylogenomic approach showed that genes involved in lipid metabolism have undergone an increased selective pressure in long-lived species, reinforcing the idea that cell membrane lipid profile has been an optimized evolutionary adaption.

The physiological role of ether lipids, and specially plasmalogens, is essentially linked to their function as membrane components. Thus, plasmalogens seem to play a key role in specific properties of cell membrane. Interestingly, an antioxidant effect has also been ascribed to plasmalogens. Effectively, the vinyl-ether linkage of the plasmalogens is particularly susceptible to oxidation by reactive species such as reactive oxygen species and hypochlorous acid, and thus, like a scavenger, could protect unsaturated membrane lipids (as well as lipoproteins) against oxidation.

Consequently, plasmalogens could have a modulatory effect on oxidative stress, lipid-derived inflammation and cell signalling mechanisms. Lipidomic studies reveal that ether lipids are inversely associated with genetic peroxisomal disorders, and also suggest that they are negatively associated with prevalent disease states such as obesity, prediabetes, type 2 diabetes mellitus, cardiovascular disease, cancer and Alzheimer's disease, among others. Notably, these pathological states share as common trait an increased oxidative stress, and a potential mechanistic role for plasmalogens.

Although the fact that systems biology-based approaches allow a comprehensive molecular characterization of complex biological systems, up to date no targeted lipidomic studies investigating differences in plasma of exceptionally long-lived humans have been reported. To this end, we have designed a study that represents the most detailed lipidomic analysis of plasma ether lipids associated with human longevity. We discovered a particular ether lipid signature related to the condition of extreme longevity, allowing the identification of potential mechanisms and biomarkers of healthy aging.

An antibody-based treatment can gently and effectively eliminate diseased blood-forming stem cells in the bone marrow to prepare for the transplantation of healthy stem cells. The researchers believe the treatment could circumvent the need to use harsh, potentially life-threatening chemotherapy or radiation to prepare people for transplant, vastly expanding the number of people who could benefit from the procedure.

The study is one of two indicating that an antibody targeting a protein called CD117 on the surface of blood-forming, or hematopoietic, stem cells can efficiently and safely eliminate the cells in mice and non-human primates. CD117 is a protein found on the surface of the stem cells. It regulates their growth and activity; the antibody, called SR1, binds to the protein and prevents its function. The results of these studies set the stage for a clinical trial of the antibody in children with an immune disorder called severe combined immunodeficiency.

Often the best chance for a cure for this and other diseases originating in the bone marrow is to eliminate the patient's own defective hematopoietic stem cells and replace them with healthy stem cells from a closely matched donor. But in order to do so, the patient must be able to withstand the pre-treatment, known as conditioning. Most conditioning regimens consist of a combination of chemotherapy and radiation in doses high enough to kill stem cells in the marrow. The researchers studied a mouse model of a class of human diseases called myelodysplastic syndromes, or MDS. People with MDS are unable to make mature, properly functioning blood cells and the only cure is a stem cell transplant. The disease primarily affects older adults, who are more likely than younger people to have additional, complicating medical factors and who are less likely to withstand the conditioning regimen.

The anti-CD117 antibody SR1 recognizes CD117 on the surface of hematopoietic stem cells isolated from either healthy donors or from patients with MDS. The researchers found that the antibody blocked the growth of both healthy and diseased stem cells in a laboratory setting. Then, the researchers investigated the effect of SR1 treatment on mice that were engineered to have a hybrid blood systems consisting of both human and mouse hematopoietic stem cells. They found in the mice that SR1 quickly and efficiently eliminated both healthy human hematopoietic stem cells and cells isolated from low-risk MDS patients. In those animals with diseased human stem cells, SR1 pre-treatment significantly improved the ability of healthy hematopoietic stem cells to engraft after transplantation.

The ends of chromosomes are covered with a kind of safety caps - telomeres. These are compact DNA sequences that stabilize chromatin structure. With each cell division telomeres become shorter, and the older a cell, the shorter are the telomeres of its chromosomes. However, certain types of cells (e.g. germ cells, stem cells, and lymphocytes) have an active immortality enzyme called telomerase. It compensates for the shortening of telomeres and allows the cells to divide practically endlessly. The highest telomerase activity is observed in cancer cells - this is one of the factors that makes them malignant.

Biochemists have now demonstrated that the activity of telomerase may be reduced using specific oligonucleotides (short DNA fragments). "We wanted to find out whether the oligonucleotides in charge of splicing shift (splicing is the process of cutting and reattaching of mRNA segments) are able to slow down the activity of telomerase. We studied it on the example of human T-lymphocytes. As a result, we managed to find an oligonucleotide able to actively suppress telomerase and slow down cell proliferation without killing the cells."

The main way of influencing the activity of telomerase is associated with the inducing of alternative splicing of its mRNA. As a result of this process several non-active protein forms are synthesized in a cell. The biochemists affected the alternative splicing using three types of oligonucleotides specific for different regulatory areas of telomerase mRNA. They were injected into human T-lymphocyte cells, and the activity of telomerase was measured after one day. It turned out that individual oligonucleotides did not influence the enzyme considerably, but the combination had a profound effect: the activity of telomerase reduced to 50% within the first 24 hours, to 18% - within the second, and to 10% - within the third.

Jim Mellon's crew at Juvenescence has found its latest venture idea in a popular diet making its rounds in biotech circles. Once again teaming up with the Buck Institute for Research on Aging, Juvenescence has launched BHB Therapeutics to explore preventative medicines that have potential to protect against age-related disease by inducing a state of ketosis, where the body burns fat instead of carbohydrates, spurring the production of anti-inflammatory ketone bodies. In particular, the biotech startup will focus on the ketone body beta-hydroxybutyrate, or - you guessed it - BHB.

Eric Verdin, the Buck president and CEO whose research inspired another Juvenescence spinout, has discovered that BHB helps the body respond to stress. A ketogenic diet - which has been heralded for its effects in weight loss, hunger suppression as well as concentration - and the consequent long-term exposure to ketone bodies can also extend healthy lifespan in model systems. Buck researchers have generated "hard scientific data" in mice that show ketosis can be cardio-protective. "The reason we think that cardio-protection may translate to humans is because if given sugar or ketones, many people's hearts prefer ketones, whereas the brain is the opposite. If given the option between sugar or ketones, the brain will take sugar. Unfortunately, individuals when they hit 50 (plus or minus a couple years) they become insulin resistant - and then the sugar can go seriously high in a variety of organs and that leads to a variety of different pathologies."

Just days ago, Juvenescence unveiled the first 46 million tranche of a promised 100 million raise that's designed to bankroll longevity projects with the collective goal of extending the human lifespan to 150 years. So far, it's ticked off stem cell tech and organ regeneration among the fields it's established itself through joint ventures with AI groups - Insilico and Netramark - and controlling interests in AgeX and LyGenesis. The goal is to have 18 projects underway by the end of the year. Look for two or three of them to be announced over the next few weeks.

A group of leading scientists devoted to research on the mechanisms of biological aging today announced the formation of the Academy for Health and Lifespan, the first global non-profit group focused on accelerating breakthroughs in the expansion of the human health span. The Academy's mission is to set the public stage for the transformation society must make, as health span extension means a growing population fully able to live healthier lives longer. The group's plan is to accomplish its goals through awareness and education, by giving new research a platform for dissemination, and by organizing conferences and forums where the world's leaders in the study of health span and longevity will gather and share research and insights. Ultimately, the Academy will provide grants to fund promising research from established and emerging scientists.

"We believe we are at a threshold moment in the research of age-related decline, which is the timing that inspired the creation of the Academy. Our shared belief is that science shows that we can age later. The Academy is a think tank seeking to speed the rate of discoveries to expand our health spans. Our 16 founders are among the leading geroscientists in the world. In addition to raising awareness of research advances among the general public, we will encourage increased public and private investment in health span and longevity research throughout the globe."

The Academy embraces a 4C mission: First to Catalyze the world's ongoing research to accelerate the development of life-changing enhancements of healthy aging. Second to Connect our founders to each other through the auspices of the academy. The third C: Convene experts and authorities around the world to advance their missions and that of the Academy's in public and private settings. Finally, we shall Communicate with the public at large to educate them about this new generation of health span and longevity research, what it means and what it doesn't mean, and to engage in constructive conversations. "As founders of AHLR, we believe that, as the field rapidly advances, we must help bridge the gap between science and public understanding. We believe that while death is inevitable, aging need not be."