The conventional wisdom is that a better understanding of the myriad roles of extracellular vesicles (EVs) in central nervous system (CNS) homeostasis is essential for developing novel therapeutics to alleviate and reverse the neurological disturbances of aging. Thus far, an increasing number of studies have revealed the complexities of EV-mediated cell-cell communications in the brain, predominantly emphasizing the role of EV released by brain cells under physiological conditions. It has been well established that EVs can cross brain barriers such as the blood-brain barrier (BBB) and brain-cerebrospinal fluid (CSF) barrier (BCsfB).

If isolated from CSF and plasma, brain EVs provide an array of options with which to learn about normal brain functions and monitor changes in the brain associated with aging or neurodegenerative pathology. Since humoral factors can enter the brain at the BBB and BCsfB, in vivo models, for example, heterochronic parabiosis (HB), heterochronic blood exchange (HBE), and infusions of small volumes of plasma or serum, have been used to uncover and better understand the role of those factors in aging and age-related diseases. Recently, using infusions of small volumes of serum, we evaluated the contribution of circulating EVs to the beneficial effect of young serum on aged muscle stem cell (MuSC) function and the skeletal muscle regenerative cascade. We demonstrated that young serum restored a youthful bioenergetic and myogenic profile to old muscle cell progeny and that this effect was dependent on circulating EVs. Yet, the full spectrum of effects of circulating young EVs on aged organs and tissues, including the brain, remains poorly understood.

In this study, we examined the effect of young serum on the cognitive performance of aged mice. We show that repeated infusions with small volumes of young serum significantly improved age-associated memory deficits and this effect was abrogated after the serum was depleted of circulating EVs. RNA-seq analysis of choroid plexus demonstrated effects on genes involved in barrier function and trans-barrier transport. Interestingly, the hippocampal transcriptome demonstrated a significant upregulation of Klotho (Kl) gene, which codes for the longevity protein Klotho, following young serum treatment. Notably this effect was abrogated after serum EV depletion, suggesting that EVs may serve as vehicles for Klotho messages from the periphery to the brain. Given the well-established role of Klotho in cognitive functioning, we performed transcriptional profiling of Klotho knockout (Klko) and Klotho heterozygous (Klhet) mice and found an association with downregulated categories such as transport, exocytosis, and lipid transport, while upregulated genes were associated with microglia.

To test if changes in transcriptomes represent transcriptomic rejuvenation, we correlated the transcriptomes of the treated mice to the most recently published chronological aging clocks, which revealed a reversal of transcriptomic aging in the choroid plexus. The results of our study indicate that further evaluation of EVs as vehicles for delivering signals from the periphery to the brain and coordinating the responses of different brain regions will open new avenues with which to expand the research and to better understand aging and rejuvenation.

After age 65, most people have two or more chronic diseases. U.S. adults in their 60s and 70s take up to five different prescription medications at a time. And what helps one condition may worsen another. At about 76, the U.S. life expectancy, the adult will probably die from one of these diseases. All of these chronic conditions share a risk factor: age. It may be the process of aging itself that makes us vulnerable to these diseases, which affects our health span (how long we stay healthy) and life span (how long we live.) As we get older, we lose strength and mobility as our bodies undergo molecular changes that eventually undermine their integrity and resiliency. Scientists refer to these changes as hallmarks. These include chronic inflammation and the accumulation of senescent cells that stop multiplying because of damage or stress but don't die as they are supposed to.

Some researchers believe that through addressing aging itself, diseases related to aging can be pushed back and possibly prevented. This would mean living healthier, longer. "The important implication is that we can study the biology of aging, start to learn about it and we have a potential to intervene in that biology to have a positive impact on disease outcomes and health." The field is known by many names: longevity, geroscience, anti-aging. Regardless of the name, it's still in the early stages. Several drugs may have the ability to postpone or prevent the onset of debilitating diseases. Animal studies have demonstrated their potential, and now clinical trials are beginning to assess whether their promise holds true in humans. "I think it's certainly legitimate to ask why we haven't done that previously. And in part it's because we really haven't had the knowledge base to be able to do that."

One promising drug is rapamycin. It's an antifungal approved by the FDA as an immune suppressor to prevent organ recipients from rejecting a new organ. Rapamycin inhibits a protein called mechanistic target of rapamycin (mTOR). The protein senses nutrients and then controls cell outputs regulating many processes in the cell. Giving rapamycin to yeast, worms, flies and mice prolonged their lives, studies have shown. Scientists began exploring rapamycin's anti-aging effects in people, and studies suggest this immune-suppressing compound can actually improve immune function in older adults boosting their response to flu shots and lowering their odds of getting severely ill during cold and flu season.

As we age, immune function both declines and increases. Though the ability of our immune system to respond to pathogens declines, it can also overreact by striking in the absence of any threat. This can result in healthy tissues and organs being attacked, which can lead to chronic inflammation linked with various kinds of diseases. So, what is causing the inflammation itself? One possible culprit is senescent cells that stop dividing but don't die. They accumulate as we get older and give off inflammatory signals, which contribute to some age-related diseases.

If a drug is ever to be used as an anti-aging therapy, it'll need to be tested in healthy people who are aging naturally the way that new drugs for a certain illness are tested on people who have that disease. However, aging isn't officially defined as a disease. One clinical trial aims to prove that aging is something that can be targeted and treated. It involves metformin, long used to treat Type 2 diabetes. In a trial called Targeting Aging With Metformin (TAME), researchers will track 3,000 adults 65 to 80, who will take the drug for six years. The goal is to see if metformin can prevent or delay three age-related diseases: dementia, heart disease, and cancer. This will show if metformin can increase health span. If the trial succeeds, it may show that drugs to target aging don't need to be expensive and can be available to more people, not just the rich.

The beating heart is a highly energy-consuming organ and the cellular energy needed to sustain contraction is primarily generated by mitochondrial oxidative phosphorylation (OXPHOS). Mitochondria are also involved in supporting various metabolic processes, as well as activation of the innate immune response and cell death pathways. Thus, the heart is highly susceptible to the effects of mitochondrial dysfunction. Mitochondria have been directly implicated as underlying drivers of cardiac aging. Studies have reported that the age-related decline in cardiac function is partly attributed to dysregulation of mitochondrial function and a decline in mitochondrial quality control. The aged heart accumulates dysfunctional mitochondria that are deficient in ATP generation and become major sources of reactive oxygen species (ROS) and oxidative stress. Interestingly, various interventions or treatments that directly or indirectly target mitochondria to reduce ROS generation, promote oxidative metabolism or enhance quality control have all been demonstrated to delay cardiac aging and alleviate disease development.

Currently, effective treatments to prevent age-related cardiovascular dysfunction are lacking, but there is a strong interest in developing therapeutics that are aimed at preserving or improving mitochondrial health in cells. Many interventions that protect against cardiac aging, including caloric restriction, exercise, and nicotinamide riboside, spermidine or rapamycin treatments, are mediated at least in part through the preservation of mitochondria. Pre-clinical studies clearly suggest that directly targeting mitochondrial ROS production or enhancing repair and turnover may have promising therapeutic benefits in the aging heart. For example, administration of the mitochondria-targeted antioxidant MitoTEMPO to aged mice reduces oxidative stress and improves systolic and diastolic function, while MitoQ administration can ameliorate vascular endothelial dysfunction in aged mice. Treatment of aged mice with the mitochondrially-targeted tetrapeptide SS-31 (elamipretide) for 8 weeks leads to reduced oxidative stress in hearts with improvements in cardiac function and reversal of cardiac hypertrophy.

There is also great interest in developing small molecules that can directly activate mitophagy in cells. VL-004 is a small molecule that increases mitophagy and longevity in C.elegans via dct-1, the worm homolog of mammalian mitophagy receptors Bnip3 and BNIP3L/NIX. VL-004 failed to extend lifespan in dct-1 mutant worms, confirming that the effect on lifespan extension is dependent on mitophagy. Although these studies targeting mitophagy are promising, whether the beneficial effects are preserved in larger organisms remains to be investigated.

Due to the longer lifespan in the population, treatments that prevent late-life morbidities and increase healthspan are urgently needed. Dysfunctional mitochondrial are clearly major contributors to cardiac aging. Although rejuvenating mitochondria to reverse or prevent aging by directly targeting mitochondrial ROS or activating mitophagy seems to have anti-aging benefits, these interventions are not without risks. ROS also function as signaling molecules in cells and complete suppression of mitochondrial ROS has adverse effects on heart function. Similarly, too much activation of mitophagy can lead to excessive clearance of mitochondria. If the clearance exceeds the cells' capacity to generate new mitochondria, it can lead to a catastrophic energy deficiency. Thus, the therapeutic window of these interventions needs to be clearly defined.

MicroRNAs (miRNAs) are a class of small noncoding RNA that can regulate physiological and pathological processes through post-transcriptional regulation of gene expression. As an important member of the miRNAs family, microRNA-7 (miR-7) was first discovered in 2001 to play an important regulatory role in tissue and organ development. Studies have shown that miR-7 participates in various tissue and organ development processes, tumorigenesis, aging, and other processes by regulating different target molecules. Notably, a series of recent studies have determined that miR-7 plays a key regulatory role in the occurrence of inflammation and related diseases. In particular, miR-7 can affect the immune response of the body by influencing T cell activation, macrophage function, dendritic cell (DC) maturation, inflammatory body activation, and other mechanisms, which has important potential application value in the intervention of related diseases.

Under normal circumstances, inflammation is a physiological defense response of the body to stimulation, involving a complex and fine-tuned regulatory process that is conducive to eliminating pathogens and promoting tissue repair. It is now known that the inflammatory process is closely related to the body's innate and adaptive immune responses, involving the activation and function of innate immune cells, such as macrophages and DCs, and adaptive immune cells, such as T cells and B cells. However, if the immune response process is abnormal, the continuous development of inflammation can lead to autoimmune or inflammatory diseases, neurodegenerative diseases, and even cancer. The inflammatory response involves innate and adaptive immune response processes mediated by immune cells with the participation of histiocytes and molecules. Therefore, the regulatory mechanisms involved in the development of inflammation and related diseases are very complex. The analysis of these mechanisms is of great significance for understanding the mechanisms of related diseases and clinical treatment.

This article reviews the current regulatory role of miR-7 in inflammation and related diseases, including viral infection, autoimmune hepatitis, inflammatory bowel disease, and encephalitis. It expounds on the molecular mechanism by which miR-7 regulates the occurrence of inflammatory diseases. Finally, the existing problems and future development directions of miR-7-based intervention on inflammation and related diseases are discussed to provide new references and help strengthen the understanding of the pathogenesis of inflammation and related diseases, as well as the development of new strategies for clinical intervention.

The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

To our knowledge, our study results are the first documentation of increased expression levels of the protein components of the CDSP pathway, namely CGAS, TBK1, RELB, P52, and P50 in the human heart samples from patients with heart failure due to DCM. These findings by showing the upregulation of expression of the CDSPs, including the components of the NFκB pathway, complement the previous data on the activation of the nuclear DDR pathway in human heart tissues from patients with DCM. The findings in the human heart samples, being devoid of the genetic manipulations, also give credence to the findings in the model organisms.

Collectively, the data implicate increased DSBs and activation of the DDR and CDSP pathways in the pathogenesis of the DCM and set the stage for further delineation of the pathogenic role of these pathways in human primary DCM. Given the salubrious effects of targeting the CDSP pathway in mouse models of DCM, the findings raise the prospects for targeting the activated CDSP pathways for the prevention and attenuation of the phenotype in human primary DCM. Given that cell stress, including transcriptional stress, is common to various forms of cardiovascular pathology, one may speculate that increased DSBs and activation of DDR and the CDSP pathways are pervasive and ubiquitous features of cardiovascular diseases.

Cardiovascular disease (CVD) cost the EU an estimated €282 billion in 2021, according to late breaking research presented at ESC Congress 2023. Health and long-term care accounted for €155 billion (55%) of these costs, equalling 11% of EU health expenditure. "CVD had a significant impact on the EU27 economy, costing a total of €282 billion in 2021. That's equivalent to 2% of Europe's GDP and is significantly more than the entire EU budget itself, used to fund research, agriculture, infrastructure and energy across the Union. By choosing not to invest in cardiovascular disease we are simply deferring the cost. This data forces us to ask the question: do we invest in cardiovascular health today or be forced to pay more at a later stage?"

This was the most comprehensive and up-to-date analysis of the economic costs of CVD to society in the EU since 2006. It is the first study to use Europe-wide patient registries and surveys rather than relying on assumptions and, unlike previous reports, includes the costs of long-term social care. The current analysis provides estimates of the societal economic costs of CVD for the 27 members states of the EU in 2021, including 1) health and social care; 2) informal care; and 3) productivity losses. The breakdown includes: €130 billion for healthcare (46%); €25 billion for social care (9%); €79 billion for informal care (28%); €15 billion in productivity losses due to illness/disability (5%); €32 billion in productivity losses due to premature death (12%). The total cost equated to €630 per EU citizen, ranging from €381 in Cyprus to €903 in Germany.

Healthcare included primary care, emergency care, hospital care, outpatient care and medications, while social care included long-term institutionalised care, and care at home. The main contributor was hospital care, which cost €79 billion, representing 51% of CVD-related care costs. CVD medications accounted for €31 billion (20%) of care costs, followed by residential nursing care homes at €15 billion (9%). Informal care costs included the work or leisure time, valued in monetary terms, that relatives and friends gave up to provide unpaid care. Relatives and friends provided 7.5 billion hours of unpaid care for patients with CVD, amounting to €79 billion across the EU.

Aging poses one of the greatest challenges for modern medicine, as it is a major risk factor for chronic diseases such as cancer, cardiovascular and neurodegenerative diseases. As the global population continues to age, there is an urgent need to develop effective interventions and diagnostic tools to prevent illness and extend a healthy lifespan, thereby reducing the burden of age-related diseases on healthcare systems.

Most basic research on aging is focused on identifying mechanisms contributing to this trait. Several hallmarks/pillars of aging have been defined and summarize the main processes underlying aging. Although these definitions are still suboptimal, they provide a nice framework used by many groups in the field to define which aspects of aging their research is focused on. One approach is to target the driving mechanisms of aging, like impaired autophagy and senescence. Inactivation of the mTOR pathway by interventions such as dietary restriction or with small molecule inhibitors like rapamycin, results in autophagy de-repression and lifespan extension (in fruit flies, worms, and mice). Extensive data suggest that rapamycin and rapalogs may have positive effects on age-related conditions and possibly on human longevity.

Cellular senescence is another potentially druggable mechanism that has been much 'in focus' to try to prevent or treat many age-associated pathologies, including cardiovascular, cerebrovascular, neurodegenerative, metabolic, and malignant diseases. Accumulated senescent cells (SenC) have deleterious effects due to the induced proinflammatory microenvironment that supports chronic low-grade inflammation ('inflammaging') and possible tumor development, and accelerate other aging mechanisms which will progress concomitantly. The depletion of SenC in aged organisms, either via genetic ablation or pharmacologically with senolytics, may have therapeutic benefits by alleviating a series of age-associated comorbidities and thus improving healthspan and even lifespan, as shown in lower organisms.

By now, research and development in the biology of aging have moved to the mainstream with initiatives by large pharmaceutical companies and funds, highlighting the growing interest in geroscience and the development of interventional gerotherapeutics. On the financing side, players like Altos Labs and Hevolution have entered the field, looking to deploy massive amounts of capital to accelerate research and commercial product development. These initiatives reflect the increasing recognition of the potential commercial impact of anti-aging therapies on healthcare and society.

Extensive research in recent years has significantly advanced our knowledge of the mechanisms underlying neural stem cell (NSC) aging and age-related decline in neurogenesis, although much remains obscure. Central to this decline is an escalating impairment of the NSC pool, characterized by increased quiescence, altered lineage specification, and progressive depletion of NSCs. The mechanisms underlying NSC aging in the dentate gyrus (DG) are complex and multifactorial. Over the course of their life, NSCs accumulate several defects, including a failure to maintain a healthy proteome, metabolic alterations, DNA damage, and epigenetic drift. It is now recognized that, in addition to intrinsic mechanisms, extrinsic changes in the NSC niche and systemic environment are the primary contributors to NSC aging, and that these mechanisms are not mutually exclusive, but rather interrelated and interacting with each other.

To safeguard the NSC pool from depletion, it is vital to gain a comprehensive understanding of the cellular and molecular mechanisms regulating NSCs and their aging. The advent of innovative new techniques such as single-cell RNA sequencing and spatial transcriptomics holds immense potential for unravelling the full complexity of the mechanisms involved in the declining capacities of NSCs during aging. Other technologies, such as CRISPR-Cas or adenovirus-mediated gene transfer, enable diverse types of gene function screens, facilitating the exploration of molecular interdependencies and their impact on NSC aging. Understanding the mechanisms that control NSC functions and their aging holds potential for the identification of novel therapeutic targets to either slow the aging process or rejuvenate aged NSCs, thereby enhancing the regenerative and cognitive capacities of the aging hippocampus.

Preventively, simple interventions with few side effects, such as diet or exercise, are particularly promising. Curatively, it becomes more difficult, as the interventional activation of NSCs usually leads to premature exhaustion and accelerated depletion of the pool. However, recent findings that have been able to identify targets whose manipulation increases the self-renewal of NSCs in the aged DG without accelerating their depletion (VEGF, combination of Plagl2 with anti-Dyrk1a) give cause for optimism.

Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of respiratory energy to heat, (5) removal of oxygen to prevent oxidative damage, and (6) generation of reactive oxygen species (ROS) as signaling molecules. Here we focus on function (6), which helps the organism control its mitochondria. The ROS bursts typically occur when the mitochondrial membrane potential (MMP) becomes too high, e.g., due to mitochondrial malfunction, leading to cardiolipin (CL) oxidation.

Depending on the intensity of CL damage, specific programs for the elimination of damaged mitochondria (mitophagy), whole cells (apoptosis), or organisms (phenoptosis) can be activated. In particular, we consider those mechanisms that suppress ROS generation by enabling ATP synthesis at low MMP levels. We discuss evidence that the mild depolarization mechanism of direct ATP/ADP exchange across mammalian inner and outer mitochondrial membranes weakens with age. We review recent data showing that by protecting CL from oxidation, mitochondria-targeted antioxidants decrease lethality in response to many potentially deadly shock insults. Thus, targeting ROS- and CL-dependent pathways may prevent acute mortality and, hopefully, slow aging.

A 2015 study implicated PU.1 as a regulator of errant microglia inflammation in a mouse model of Alzheimer's disease. Genetically knocking down PU.1 in the body is not a viable therapeutic strategy given its importance in normal healthy function. Researchers therefore screened more than 58,000 small molecules from libraries of FDA-approved drugs and novel chemicals to see if any could safely and significantly reduce key inflammation and Alzheimer's related genes regulated by by PU.1 in cell cultures. After several rounds of increasingly stringent screening, they narrowed the field down to six chemicals. A11 was by far the most potent among them.

Researchers tested the effects of A11 doses on the function of human microglia-like cells cultured from patient stem cells. When they exposed the microglia-like cells to immune molecules that typically trigger inflammation, cells dosed with A11 exhibited reduced expression and secretion of inflammatory cytokines and less of the cell body shape changes associated with microglia inflammatory responses. The cells also showed less accumulation of lipid molecules, another sign of inflammatory activation. Looking at gene expression patterns, the scientists observed that A11-treated cells exposed to inflammatory triggers behaved much like unperturbed microglia, suggesting that A11 helps prevent microglia from overreacting to inflammatory cues.

In a new paper, researchers started with experiments to further validate that PU.1 would be a therapeutically meaningful target. To do that the scientists compared gene expression in immune cells of postmortem brain samples from Alzheimer's patients and mouse models and matching non-Alzheimer's controls. The comparisons showed that Alzheimer's effects major changes in microglial gene expression and that an increase in PU.1 binding to inflammatory gene targets was a significant component of that change. Moreover, they showed that reducing PU.1 activity in a mouse model of Alzheimer's reduced inflammation and neurodegeneration, the death of neurons.

Two more lab tests aimed at understanding how A11 exerts its effects revealed that it doesn't change PU.1 levels. Instead it counteracts PU.1 activity by recruiting several proteins including MECP2, HDAC1, SIN3A and DMNT3A, known to repress expression of its targets. Essentially amid Alzheimer's disease, A11 tamps down what PU.1 amps up.

Durable reconstitution of the distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising therapy for diseases that result from alveolar damage. Here, we differentiate murine PSCs into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. After transplantation, these progenitors mature in the distal lung, assuming the molecular phenotypes of alveolar type 2 (AT2) and type 1 (AT1) cells.

After months in vivo, donor-derived cells retain their mature phenotypes, as characterized by single-cell RNA sequencing (scRNA-seq), histologic profiling, and functional assessment that demonstrates continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lung's facultative progenitor and differentiated epithelial cell compartments with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy that can be utilized to better understand the mechanisms and utility of engraftment.

The thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity and undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive immunity. By characterizing cortical and medullary compartments in the human thymus at single-cell resolution, in this study we have defined specific epithelial populations, including those that share properties with bona fide stem cells (SCs) of lifelong regenerating epidermis.

Thymic epithelial SCs display a distinctive transcriptional profile and phenotypic traits, including pleiotropic multilineage potency, to give rise to several cell types that were not previously considered to have shared origin. Using here identified SC markers, we have defined their cortical and medullary niches and shown that, in vitro, the cells display long-term clonal expansion and self-organizing capacity. These data substantively broaden our knowledge of SC biology and set a stage for tackling thymic atrophy and related disorders.

Cardiovascular disease and dementia frequently occur together in elderly people. Nevertheless, few longitudinal studies have examined how atherosclerosis and its associated risk factors affect brain health from middle age. Now, a new study provides data on this relationship; the results confirm the importance of controlling traditional cardiovascular risk factors, such as hypertension, cholesterol, diabetes, smoking, and a sedentary lifestyle, not only to preserve cardiovascular health, but also to prevent Alzheimer's disease and other dementias.

In 2021,scientists discovered that the presence of cardiovascular risk factors and subclinical (presymptomatic) atherosclerosis in the carotid arteries (the arteries that supply the brain) was associated with lower glucose metabolism in the brains of apparently healthy 50-year-old participants in the PESA-CNIC-Santander study. Glucose metabolism in the brain is considered an indicator of brain health. Glucose is the main energy source for neurons and other brain cells. The PESA-CNIC-Santander study is a prospective study that includes more than 4,000 asymptomatic middle-aged participants who have been exhaustively assessed for the presence and progression of subclinical atherosclerosis since 2010.

Researchers have continued to monitor the cerebral health of these participants over 5 years. Their research shows that individuals who maintained a high cardiovascular risk throughout this period had a more pronounced reduction in cerebral glucose metabolism, detected using imaging techniques such as positron emission tomography (PET). "In participants with a sustained high cardiovascular risk, the decline in cerebral metabolism was three times greater than in participants who maintained a low cardiovascular risk. The individuals showing this metabolic decline already show signs of neuronal injury."

Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage.

Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.

Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability.

Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in somatic cells also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.