Repair Biotechnologies is a newly funded biotech startup developing treatments to reverse the progression of immunosenescence and atherosclerosis in old age. We are developing gene therapy and recombinant protein approaches to meaningfully address these widespread and harmful age-related conditions. Do you want to be involved in making an enormous positive difference to the lives of tens of millions of older patients? We have an immediate opening for our first technical lead in Lafayette, NY; a PhD with experience in molecular biology, gene therapy, cell and animal studies, able and proven to perform original research at the highest level of quality.

You will be helping us to define and complete our early stage development programs, working in the environment of an admired, busy, and expanding biotech incubator. You will design, execute, and troubleshoot cell and animal studies, in a critical position to guide the success of these programs as they move towards regulatory approval. You will be responsible for ensuring the quality and documentation of the work as it progresses. As new team members come on board, you will be setting a high bar and mentoring their development as researchers.

The ideal candidate will be detail oriented, recognize that we all live and die by the quality of our documentation, be able to produce quality work in a fast-paced and flexible environment, collaborate well with fellow scientists, and demonstrate the ability to learn and grow as our company expands to meet the challenges of building effective treatments to reverse aspects of aging. The qualifications:

• PhD in cell biology, biochemistry, genetics, or related field (ABD acceptable).
• Technical expertise in recombinant protein expression and/or viral vector production.
• Experience in cell culture and assay development required.
• Experience in husbandry, gene therapy, and biologic drug discovery and development are preferred but not required.
• Must be able to operate independently and as a part of a team for execution of projects of varying scale.

LaFayette is a beautiful part of New York state with exceptional quality of life and low cost of living. Health benefits, competitive salary, and employee equity in the company are offered. Interested? Send your CV to info@repairbiotechnologies.com.

Researchers were able to explain why resident immune cells in fat tissue - immune cells that are thought to be beneficial - turn harmful during obesity, causing unwanted and unhealthy inflammation. The research team found that damaging "free radicals" produced within our bodies react with substances known as lipids inside fat tissue. That results in a process called "lipid oxidation." At first the scientists expected the oxidized lipids would prove harmful, but it wasn't that simple. Some of the oxidized lipids were causing damaging inflammation - reprogramming immune cells to become hyperactive - but other oxidized lipids were present in healthy tissue. Specifically, shorter "truncated" ones are protective, while longer "full-length" ones were inflammatory.

Now that scientists know which oxidized lipids are causing problems, and how, they can seek to block them to prevent inflammation. They may be able to develop a drug, for example, that would reduce the number of harmful, full-length oxidized lipids. Alternately, doctors might want to promote the number of beneficial, shorter phospholipids. "Inflammation is important for your body's defenses, so you don't want to eliminate it completely. It's a question of finding the right balance."

Macrophages sense pathogen-associated molecular patterns as well as endogenously formed danger-associated molecular patterns (DAMPs) derived from cell and tissue damage to adapt their functional phenotype and cellular metabolism. Because oxidative stress is a hallmark of highly metabolic healthy tissue, as well as inflamed tissue, the formation of oxidation-derived DAMPs is an important signal for macrophage adaptation to oxidative tissue damage.

In adipose tissue, accumulating evidence supports a role for adipose tissue macrophages (ATMs) in regulating tissue-specific glucose homeostasis and inflammation. Both insulin sensitivity and obesity-associated insulin resistance are affected by tissue redox homeostasis and oxidative stress. However, whether ATMs play a role in regulating tissue redox homeostasis remains unknown. Furthermore, how ATMs adapt to tissue oxidation status is unknown.

We have previously shown that oxidized phospholipids (OxPL) induce the formation of the Mox phenotype in macrophages by inducing Nrf2-dependent gene expression. Recently, we found that OxPL redirect macrophage metabolism and bioenergetics to support production of antioxidant metabolites, but also promote a low level of inflammation via Toll-like receptor 2 (TLR2). However, individual OxPL species promote different cellular responses. This implies that the relative abundance of individual OxPL species within tissues determines cellular responses and metabolic adaptation.

Here we characterize the bioenergetic profile of ATMs from lean and obese mice. We used flow cytometry to link the ATM bioenergetics profile to established in vitro macrophage polarization states (i.e., proinflammatory M1, antiinflammatory M2, or antioxidant Mox). Furthermore, quantification of individual OxPL species in whole blood and the ATM-containing stromal vascular fraction (SVF) of adipose tissue allowed us to define the unique OxPL compositions present in physiological and pathological states of obesity. Finally, we tested the different OxPL compositions that we found in vivo on their ability to differentially reprogram macrophage bioenergetics and phenotypic polarization states in vitro.

The rapid regeneration of the intestinal epithelium is enabled by fast-cycling Lgr5+ intestinal stem cells (ISCs) crowded into the base of the intestinal crypt. ISCs are not only limited in number and location, but also arranged in a specific pattern. Aging is one of critical factors which gradually decreases the functionality of stem cells, including diminishing the self-renewal ability of stem cells, which impairs the balance between stem and differentiated cells. Aging also weakens cellular functions, such as mitigating reactive oxygen species and DNA damage. However, how aging affects specific behaviors such as the patterning of intestinal crypt still not known.

To investigate the robustness of the patterning and its maintenance in vivo, we ablated individual cells in the crypt with high-pulse-energy femtosecond laser ablation and imaged the real-time dynamics of recovery with multiphoton microscopy. Such accurate manipulation is not achieved by current methods of radiation, chemical treatment, or genetic ablation of specified lineages. Surprisingly, after ablation of a small number of cells, migration of neighboring cells was sufficient to reestablish cellular contacts and the alternating pattern in the crypt base within hours, before any cells divided.

In addition, we observed coordinated motion of the cells at the edge of the crypt base that expelled debris out towards the lumen. The repair movements were impaired by both inhibition of cellular movement and aging, highlighting the importance of this dynamic response for the integrity of the niche. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Reduction of this newly-identified behavior of stem cells could contribute to disease and age-related changes.

For any factor to be considered a hallmark of aging, it should meet the following criteria: (I) it should be present during normal aging; (II) its exacerbation should trigger an accelerated aging; and (III) its amelioration should prevent the normal aging course, even extending lifespan. Accordingly, one of the most relevant features of aging is related to the increasingly dysfunctional mechanisms of renewal of cellular constituents that precludes the clearance of damaged biomolecules and organelles and its replacement by new functional structures. This sustained inefficient recycling mechanism leads to the accumulation of unfit molecules that further interfere with cellular functions, preferentially within long-lived post-mitotic cells such as neurons. Among the main components of this biological "garbage," we could find indigestible protein aggregates, defective mitochondria, and lipofuscin (LF).

LF is a fluorescent complex mixture composed of highly oxidized cross-linked macromolecules with multiple metabolic origins. The nature and structure of LF complexes seem to vary among tissues and show temporal heterogeneity in composition of oxidized proteins (30-70%), lipids (20-50%), metals cations (2%), and sugar residues. Because of its polymeric and highly cross-linked nature, LF cannot be degraded, nor cleared by exocytosis, thus being accumulated within the lysosomes and cell cytoplasm of long-lived post-mitotic and senescent animal cells. Opposite, proliferative cells efficiently dilute LF aggregates during cell division, showing low or no accumulation of the pigment. For this reason, LF deposits are especially abundant in nerve cells, cardiac muscle cells, and skin.

LF is considered a hallmark of cellular aging. In normal aged mammal brains, LF distributes delineating a specific senescence pattern that correlates with altered neuronal cytoskeleton and cellular trafficking. Thus, as we age, the brain of the human adult becomes heavily laden with intraneuronal deposits of LF and neuromelanin pigment. However, in neurodegenerative disorders, LF aggregates appear to increase not only with age but also with pathological processes such as neuronal loss, proliferation, and activation of glial cells, and a repertoire of cellular alterations, including oxidative stress, proteasome, lysosomal, and mitochondrial dysfunction.

In order to discuss whether LF is a subproduct of defective cellular homeostasis associated with aging or it has a pathological role of its own in neurodegeneration, it is relevant to compare the temporal profile of accumulation of LF aggregates with pathognomonic protein deposits associated with diverse neurodegenerative disorders. Interestingly, the temporal pattern of accumulation is similar to the one observed for protein deposits in different neurodegenerative disorders. Data suggests a neuropathological role of LF by impairing the same mechanisms and acting like other protein aggregates (e.g., amyloid beta, tau, alpha-synuclein) of different neurodegenerative diseases.

It turns out that the lymphatic vessels long thought not to exist in the brain are in fact essential to the brain's ability to cleanse itself. New work gives us the most complete picture yet of the role of these vessels - and their tremendous importance for brain function and healthy aging. Researchers were able to use a compound to improve the flow of waste from the brain to the lymph nodes in the neck of aged mice. The vessels became larger and drained better, and that had a direct effect on the mice's ability to learn and remember.

The researchers determined that obstructing the vessels in mice worsens the accumulation of harmful amyloid plaques in the brain that are associated with Alzheimer's. This may help explain the buildup of such plaques in people, the cause of which is not well understood. "In human Alzheimer's disease, 98 percent of cases are not driven by known genetic differences, so it's really a matter of what is affected by aging that gives rise to this disease. As we did in mice, it will be interesting to try and figure out what specific changes are happening in the old brain lymphatics in humans so we can develop specific approaches to treat age-related sickness."

Impairing the vessels in mice had a fascinating consequence: "What was really interesting is that with the worsening pathology, it actually looks very similar to what we see in human samples in terms of all this aggregation of amyloid protein in the brain and meninges. By impairing lymphatic function, we made the mouse model more similar to human pathology." The researchers now will work to develop a drug to improve the performance of the lymphatic vessels in people.

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. Rediscovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice.

Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer's disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer's disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases.

The room at the clinic in Bogota was clean and spare. There was a bed and, on her right, an IV drip. Over a period that lasted well into the night, there would be more than 100 injections. The pace was agonizingly slow. "So you're saying this will still get to my organs, right?" she asked the doctor as he inserted a needle below her kneecap. It would, he assured her. It was after midnight when she got the last injection.

It was September 16, 2015, and a strange kind of medical history had been made: in an untested procedure that would have violated federal regulations in the U.S., Elizabeth Parrish, a healthy 44-year-old the founder of a small biotech startup called BioViva, had received what she believed was a more potent dose of gene therapy than any other person ever had. She did it to fight what she called the "disease" of aging. She was, in her own words, Patient Zero in the quest for radically increased longevity.

Testing BioViva's products first on herself, Parrish said, had been the only ethical choice. She hadn't turned back into a 25-year-old. Nor, on the bright side, did she appear to have cancer. Her biomarkers - triglycerides, C-reactive protein, muscle mass - were promising but ultimately inconclusive, since they were the results of just one person, and not published in a peer-reviewed study. The results of Parrish's telomere tests showed average length in white blood cells had increased by 9 percent. A press release said that this was equivalent to reversing 20 years of aging. But there was no published study to go along with it, and the news was easy to dismiss.

For two years, Parrish had been claiming that BioViva would soon open overseas clinics. Not long before RAADfest 2016, she and Bill Andrews of Sierra Sciences had made a coordinated announcement: they were partnering in a new venture called BioViva Fiji. They showed off an architectural rendering of a generically modern gene-therapy clinic. When the Fijian press caught wind of BioViva Fiji, authorities told journalists that it didn't exist, not even on paper. And at RAADfest 2017, neither Parrish nor Andrews seemed too keen to talk about it anymore.

It was the prelude to a breakup, a friendly (and perhaps temporary) parting of ways. In December 2017, a new company called Libella Gene Therapeutics announced that it had secured an exclusive license from Bill Andrews for his AAV Reverse (hTERT) transcriptase enzyme technology. Libella was now recruiting patients for a first-ever study in Cartagena, Colombia. There was no mention of BioViva, no mention of Parrish, no mention of her self-experiment.

Parrish and I met for lunch so she could tell me about BioViva's new direction. "So, BioViva is now a bioinformatics company!" she announced. It was pivoting. It wasn't trying to do clinical trials for the time being. Even offshore, away from the FDA, they cost millions, and raising that kind of money to do traditional trials would amount to the kind of slow-moving medicine she was trying to overcome. BioViva would be a data platform for other companies, collecting and analyzing the information they gathered from their trials.

When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.

Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive. In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders, and cancer.

The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive. The wrinkled skin showed changes similar to those seen in both intrinsic and extrinsic aging - intrinsic aging is the natural process of aging, and extrinsic aging is the effect of external factors that influence aging, such as skin wrinkles that develop from excess sun or long-term smoking.

Among the details, the skin of induced-mutation mice showed increased numbers of skin cells, abnormal thickening of the outer layer, dysfunctional hair follicles and increased inflammation that appeared to contribute to skin pathology. These are similar to extrinsic aging of the skin in humans. The mice with depleted mitochondrial DNA also showed changed expression of four aging-associated markers in cells, similar to intrinsic aging.

Vascular aging is associated with impaired endothelial function, low-grade inflammation, and markedly increased aortic stiffness. Aging is associated with fragmentation of elastin and increased amounts and cross-linking of collagen, all of which increase the passive stiffness of the extracellular matrix. However, it has also been proposed that aging of the vascular smooth muscle cell (VSMC) can adversely modulate the fractional engagement of collagen, leading to a dynamic increase in stiffness. In fact, recent studies in a mouse model, where viable smooth muscle preparations can be readily obtained and activated with vasoactive agents to measure active stiffness, have demonstrated that close to half of the total stiffness of the aortic wall is attributable to the active stiffness of the VSMC, with the remaining fraction due to the extracellular matrix.

In addition to the passive stiffness of the matrix, there are at least two dynamic components that contribute to the material stiffness of the VSMC: first, the attachment of cycling crossbridges in the contractile filaments, and, second, the regulated transmission of force and stiffness through a nonmuscle actin cytoskeleton connected to focal adhesion (FA) complexes. The stiffness and plasticity of this nonmuscle actin cytoskeleton are regulated by proteins that control branched and linear actin polymerization such as N-WASP and VASP, respectively.

The nonmuscle actin cytoskeleton and FAs to which it is attached have been shown to display plasticity. Plasticity of the cortical cytoskeleton of VSMCs may contribute to the function of the healthy, compliant proximal aorta, acting as a tunable "shock absorber" that adapts in order to limit transmission of excessive pulsatile energy into the delicate downstream microvessels. This plasticity of the cortical cytoskeleton of the aorta in young mice has been shown to utilize a Src-dependent signaling pathway that promotes tyrosine phosphorylation of FA proteins. We have found that attenuated activity of this pathway with aging is associated with stiffening, measured ex vivo in a mouse model.

In the present study we tested the hypothesis that specific cytoskeletal protein-protein interfaces that no longer remodel in the aged aorta could be competed with by decoy peptides to reduce increases in aortic stiffness of proximal aortas taken from aged mice. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness.

An obvious difference between men and women are the sex chromosomes, which could impact aging and longevity in a number of ways. A first obvious effect of having sex chromosomes is that males have one X and are hemizygous for that chromosome while females have two Xs. In women, however, X-chromosome inactivation (XCI) means that only one X is expressed in each cell. This implies that if present in a male, a deleterious mutation on the X will always be expressed. If present in a female, it will depend whether the mutation is recessive or dominant and whether that female is homozygous or heterozygous for this mutation. This mechanism, called the "unguarded X", could contribute to aging and longevity.

A general prediction of the unguarded X is that, in XY systems, males should die faster. In some species (e.g., birds, butterflies), females are heterogametic (i.e., have different sex chromosomes); these systems are called ZW (females: ZW, males: ZZ). The W is equivalent to the Y and the Z to the X. In these systems, the unguarded Z effect should result in the opposite pattern: ZW females should die faster. Until recently, however, very little data was available and they tended to support the idea that sex chromosomes would not have a major role in sex-specific aging patterns.

Some recent data have changed this view. Researchers have investigated the connection between sex chromosomes and aging/longevity by compiling data on adult sex ratios (ASRs) as a proxy for the sex gap in longevity and sex chromosome types (XY, ZW) for 344 species of tetrapods (including mammals, birds, lizards, crocodiles, snakes, amphibians), by far the largest dataset analyzed so far. They found a strong statistical association between the sex chromosome type and ASRs. In the XY species, ASRs are female-biased, which suggests that males tend to die younger, whereas it is the opposite pattern in ZW species.

Some other recent data suggests that the unguarded X/Z might be just one mechanism among several. In Drosophila, the Y chromosome, despite its very small gene content, has a major effect on the epigenetics of the other chromosomes. In old male flies, Y chromatin is more open and transposable elements tend to be de-repressed, which could result in those elements jumping around in the male genome, causing deleterious mutations and speeding up aging. To further test the idea that the Y chromosome causes faster aging in males than in female flies, researchers looked at aging and longevity in XXY females and monosomic X and XYY males, and confirmed that the Y increases aging in Drosophila. This suggests that sex chromosomes may contribute to aging through a "toxic Y/W" effect because of particularly high transposable element content.

Cellular senescence is a state of permanent cell cycle arrest that is induced by diverse types of stress associated with oncogene activation, DNA damage, or chromatin deregulation and can have tumor-suppressive effects. However, senescent cells also have profound deleterious effects that enhance tumor malignancy or contribute to tissue dysfunction in aging and disease. Indeed, senescent cells undergo dramatic alterations in metabolic and gene expression profiles with acquisition of a senescence-associated secretory phenotype (SASP). Through the SASP, even relatively low levels of senescent cells can have far-ranging effects that influence tissue function.

In the human genome, ribosomal DNA (rDNA) genes comprise ∼350 copies distributed in large clusters. As in yeast, mammalian rDNA genes are prone to instability, and recombination among repeats can lead to expansions, contractions, or translocations. Thus, maintaining rDNA stability is a serious challenge for genome integrity, and rDNA instability is a potential driving force of genomic instability in cancer.

In mammals, there are seven sirtuins, and a growing body of work has implicated these enzymes in protecting against diverse aging-related pathologic states from cancer to metabolic and neurodegenerative diseases. SIRT7 is the only mammalian sirtuin that is concentrated in nucleoli, subnuclear compartments where rDNA genes are located, and early studies found that SIRT7 binds rDNA regulatory sequences. Surprisingly, however, SIRT7 was found to stimulate rather than repress rDNA transcription. Recent work has also implicated SIRT7 in various aspects of DNA double strand break (DSB) repair and DNA damage signaling. However, no studies have examined potential effects of SIRT7 on nucleolar DSBs at rDNA loci.

Several reports have now implicated SIRT7 in regulation of mammalian aging. Decreased SIRT7 expression is observed in certain tissues with aging, and loss of SIRT7 in mice leads to shortened lifespan. However, much remains to be learned about the underlying molecular mechanisms through which SIRT7 influences aging pathology. Here, we report a novel role of human SIRT7 in protecting against cellular senescence by maintaining heterochromatin silencing and genomic stability at ribosomal DNA gene clusters. Our findings provide the first demonstration that rDNA instability has a causal role in triggering acute senescence of primary human cells and show that SIRT7-dependent heterochromatin silencing is a key mechanism protecting against this process.

Freedom is a rather big deal in this age. Different kinds of freedom are available in different amounts in different areas of the world, and while many people tend to see the glass half empty and complain that freedom is not equally distributed everywhere, it's undeniable that we enjoy far greater liberty than previous generations. It's not always easy to act upon your choices, and sometimes you're free to choose in theory but not in practice, but overall, we enjoy options that who came before us couldn't even dream of.

Take health, for example. Two hundred years back, if you didn't want to get the flu, or any other infectious disease, you didn't have the option not to do so. The mechanism through which infectious diseases manifest and spread wasn't even remotely understood, so you didn't have any idea what you should or shouldn't do to minimize your risk of falling ill; basic hygiene wasn't exactly a standard, and drugs and vaccines were nowhere in sight. Today, however, if you want to avoid infectious diseases, you have plenty of options to do so.

The vast majority of diseases and ailments that we still cannot really cure or prevent are the diseases of old age, and they range from being a hindrance to being debilitating and lethal. Giving people the option to be free from the diseases of aging is literally all that life extension is about. Right now, we're all sitting on a fast train heading towards disability, disease, loss of independence and dignity, suffering for ourselves and our loved ones, and, ultimately, death.

Indirectly, life extension also means having more control over how long you'd like to live, because a longer life is only the logical consequence of being healthier for longer. To me, the idea of wanting to live for only a finite amount of time sounds absolutely absurd, but that's my problem; there may well be people who have their own reasons to want to live only so long. If life extension were possible, at the very least, you would have the option to live longer, and in a best-case scenario, you'd have an option to live in perfect health for as long as you see fit. Right now, you don't have that option. In this regard, your freedom is severely limited. This is all that life extension means: the freedom to be healthy and control how long you want to exist.

My mission in this book is two-fold. First, to cover some of the ideological assumptions which underlie cryonics as an emerging technology. Second, to propose that cryonics is financially feasible for you, if you are fairly healthy and have some reasonable financial resources. Here are a few ideas I would like you to consider.

Cryonics is a legitimate though currently unproven medical technology. Assuming this, you may want to be in the cryonics "experimental group" and not in the "control group." This choice may be affordable for you through the leverage of life insurance. If cryonics does indeed work and you are revived, it will probably be in a really spectacular and fun future. There are resources and people to help you in your research and decision making. I am one of those people.

Yes, it just may be possible for you to beat death and taxes! This book is written to explain why that sentence is not as unlikely as it may seem. I acknowledge that this is a mind-stretching claim, and I welcome your skepticism. This book will explain how and why most individuals might reasonably incorporate the amount of money required for cryopreservation into their budget. This is generally accomplished through the financial leverage of life insurance, where a relatively small amount of premium paid to an insurance company blossoms to an enormous amount of money on pronoucement of "death".

At that point, when an individual is pronounced "dead" by current legal (not necessarily medical) standards, any life insurance policies are fully collectible and will be paid out. What this means, in practical terms, is that nearly everyone reading these words, and I do include you, dear reader, now has the financial ability to afford this potentially life-preserving technology.

OncoSenX is a late stage pre-clinical cancer company. OncoSenX targets solid tumors based on transcriptional activity using a unique lipid nanoparticle and plasmid DNA. The next generation in cancer therapies will be more targeted with less side effects. At OncoSenX we believe the battle against cancer should be fought with genetic information. Our treatment delivers a simple program that induces apoptosis in cancerous cells. Our approach is a less invasive, more precise intervention for this complex and devastating disease.

Our system is comprised of two main components: An untargeted non-toxic lipid nanoparticle and a highly targeted DNA payload. DNA plasmids encode an inducible death protein under a promoter that is active in the target cell population. We are initially targeting cells that are transcriptionally active for p53. Cells are killed via apoptosis with caspase 9. We can use our DNA payload to effectively implement logic gates (IF / OR / AND). This allows us to precisely target cell populations based on their genetic activity without harming adjacent cells.

Our patented lipid nanoparticle (LNP) is the transfection agent that efficiently delivers our non-integrating DNA plasmid to cancer cells. These LNPs have been shown to be non-immunogenic, even with adjuvant, and are non-toxic at doses up to 10x expected human therapeutic dose in rodents and non-human primates.

Many primate species engage in unidirectional or reciprocal cooperation with others. Dyadic interactions with relatives or other individuals are particularly common among humans. This cooperative behaviour has presumably evolved because it increases the fitness of the individual who performs the behaviour by yielding either indirect or direct fitness gains. Direct fitness gains via reciprocity are often not immediate but rather occur with a time delay to be realised in a future interaction between the cooperation partners.

A human baby born today in an industrialised country can expect to share most of its lifetime with a peer from its birth cohort due to high lifespan equality (i.e. most individuals live similarly long). High lifespan equality arises from a rectangularised survival function, which captures the fact that most individuals will survive to a similar age. What is true for humans today, however, need not be true in general. Across the tree of life, species show an astounding diversity of survival functions, with remarkable differences even between human populations. In this work we ask how different survival functions determine, firstly, life expectancy, secondly, the expectancy of overlapping life among two peers of a birth cohort ("shared life expectancy"), and thirdly, the proportion of shared life expectancy in relation to life expectancy ("proportion of life shared"). A low proportion of life shared adds uncertainty to the future availability of reciprocal cooperation partners and thus may hinder the evolution of cooperation.

Using population models, we find that while the proportion of life shared can vary vastly for similar life expectancies, almost all changes to mortality schedules that result in higher life expectancies also result in higher proportions of life shared. From our results we can infer that selection pressures which increase life expectancy almost always increase the proportion of life shared, or in other words lifespan equality, and vice versa. A co-occurrence of both carries therefore little indication as to whether high proportions of life shared may aid the evolution of high life expectancies through enhancing cooperative behaviour, or whether high life expectancies inevitably co-occur with high proportion of life shared, which then may be a precondition for the evolution of cooperation.

The human digestive tract is inhabited by numerous microorganisms. Bacteria outnumber all other members of the gut microbial community, and the total number of bacterial species found in the gut is estimated to be about 500-1,000. The most populous bacterial phyla, constituting more than 90% of the gut microbiota are Bacteriodetes and Firmicutes. The remainder consists of many species in other phyla in lower abundance, some of which may provide important metabolites and functions for healthy aging.

Individual gut microbiotas show distinct profiles, and this inter-individual variation is greater in older adults. Longitudinally, however, gut microbiotas of healthy adults are relatively stable even for decades. Thus, once established early in life (even within 3 years after birth), the gut microbiota seems to be rather stably maintained. Nevertheless, it is responsive to the host's dietary and health conditions, much as the host's epigenome is to various environmental cues. In fact, the gut microbiota interfaces the gut environment with the epigenome, but its communication with the host systems involves various signaling networks and their mediators. For instance, the "gut-brain axis" connects the gut microbiome with the central nervous system via neurons, hormones, or cytokines.

Despite variation between individuals, most adult age groups, from young to extremely old, seem to possess a common core function in their microbiomes that is provided by members of abundant taxa. If so, what is important in the gut microbiota for healthy aging could be a compositional change in the functional core microbiome or an enrichment of non-core functions with advancing age.

With advancing chronological age, the gut microbiota becomes more diverse. However, when biological age is considered with adjustment for chronological age, overall richness decreases, while certain bacterial taxa associated with unhealthy aging thrive. Thus, as biological age increases, the homeostatic relationship between the gut microbiota and the host deteriorates, while gut dysbiosis increases. These dysbiotic changes in the aging gut can negate the beneficial effects of the gut microbiome on the nutrient signaling pathways, and provoke proinflammatory innate immunity and other pathological conditions.