New findings show that healthy bone marrow cells were prematurely aged by cancer cells around them. It is well known that ageing promotes cancer development. But this is the first time that the reverse has been shown to be true. Importantly, the aged bone marrow cells accelerated the growth and development of the leukaemia - creating a vicious cycle that fuels the disease. The study also identified the mechanism by which this process of premature ageing occurs in the bone marrow of leukaemia patients and highlights the potential impact this could have on future treatments.

NOX2, an enzyme usually involved in the body's response to infection, was shown to be present in acute myeloid leukemia (AML) cells - and this was found to be responsible for creating the ageing conditions. The research team established that the NOX2 enzyme generates superoxide which drives the ageing process. By inhibiting NOX2, researchers showed the reduction in aged neighbouring non-malignant cells resulted in slower cancer growth.

Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of pro-inflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the bone marrow microenvironment. We report that the bone marrow stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feedback to promote AML blast survival and proliferation via the SASP.

Importantly, selective elimination of p16INK4a-positive senescent bone marrow stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model we show that by targeting NOX2 we reduced bone marrow stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia generated NOX2 derived superoxide as a driver of pro-tumoral p16INK4a-dependent senescence in bone marrow stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs which specifically target the 'benign' senescent cells that surround and support AML.

Loss of Proteostasis

Proteostasis is one of the major functions of autophagy in normal tissues. Imbalance of proteostasis due to aging leads to protein aggregation, accumulation of misfolded proteins and in the end to cellular dysfunction, among others. Notably, carbonylation due to oxidative stress is one of the changes that leads to loss of proteostasis. To avoid cell death or dysfunction, numerous homeostatic mechanisms turn on, mainly autophagy and the Ubiquitin-Proteasome-System (UPS). Because autophagy is considered one of the most important intracellular homeostatic processes, an alteration or deterioration of this pathway could modify the normal cell functioning, including a variety of diseases and normal cell physiology declination.

Mitochondrial Dysfunction

Mitophagy is a basal process involved in the autophagic degradation of mitochondria. It is necessary in normal differentiation of certain cell types such as red blood cells, in embryogenesis, immune response, cell programming, and cell death. Mitophagy is required not only to remove damaged mitochondria, but also to promote the biosynthesis of new ones, supporting the mitochondrial quality control. Given that mitochondria are implicated in bioenergetics and ROS production, the mitophagy plays an important role in cell homeostasis. Additionally, a decrease in mitophagy is observed in aged animals and this contributes to aging phenotypes.

Deregulated Nutrient Sensing

Because autophagy is a catabolic mechanism, it can be assumed to be implicated in cellular and systemic metabolism. Metabolic stress responses could be compromised due to a decline in autophagic activity. As an important process regulating the general cellular status, autophagy can also link metabolic pathways to maintain homeostasis under a variety of conditions. In this sense, it has been demonstrated that, after nutrient or growth factor deprivation, ULK1 and ULK2 are activated, and these kinases phosphorylate and activate several glycolytic enzymes as well as autophagic proteins. This makes it possible to obtain metabolites thanks to glucose uptake, gluconeogenic pathway blockage, and autophagic degradation of cytosolic components. Supporting this, mTOR hyperactivation was found in several diseases such as obesity, metabolic syndrome, and type 2 diabetes, which highlights the importance of a tight regulation of autophagy as well as the nutrient sensing pathway.

Genomic Instability

In the last decade, several studies have demonstrated that autophagy or autophagic-related molecules act as a "safeguard" of genome stability both directly (DNA repair modulation) and indirectly (by acting as a homeostatic response). Several mouse models have provided substantial information regarding genomic instability and its connection with healthy and pathological aging.

Epigenetic Alterations

Taken together, organismal models as well as in vitro studies highlight the importance of epigenetics throughout life. The relationship between epigenetic changes and autophagy needs to be deeply studied in order to understand the regulatory loop that seems to be involved in development and aging.

Telomere Attrition

Telomerase activity can support cell cycle progression by preventing the arrest due to short telomeres, leading to a putative malignancy. Remarkably, overexpression of Beclin1 in HeLa cells revealed that telomerase activity is reduced after autophagy induction. This approach argues in favor of the hypothesis that autophagy plays an important tumor suppressor role by the modulation of telomerase activity in somatic cells. This autophagic response arises in order to avoid genome instability and telomeric dysfunction, thus promoting cell survival.

Cellular Senescence

Autophagy regulates the senescence of vascular smooth muscle cells. Intriguingly, autophagy can mediate the transition to a senescent phenotype in oncogene-induced senescence fibroblasts, making possible the protein remodeling needed to establish the senescent phenotype under oncogene activation. It is proposed that type of autophagy, the exact moment when it acts, and the place where it occurs can define the pro or anti-senescence role of autophagy.

Stem Cell Exhaustion

Self-renewal is important to maintain the population of tissue-specific stem cells throughout life. Importantly, as we age, stem-cell activity decreases. It has been shown that autophagy is necessary for preservation and quiescence of hematopoietic stem cells (HSCs). Autophagy is also important to maintain stemness in bone marrow-derived mesenchymal stem cells. In addition, Atg7 loss in aged muscle stem cells (satellite cells) of transgenic mice caused altered mitophagy and an accumulation of ROS, all features of senescence that diminish the regenerative potential of aged satellite cells.

The mechanisms by which senescent cells (SCs) accumulate with aging have not been fully understood but may be attributable in part to immune senescence that decreases the ability of the body to clear SCs. Although cellular senescence is a tumor-suppressive mechanism, SCs can play a causative role in aging and age-related diseases when they accumulate. This suggestion is supported by the finding that genetic elimination of SCs in naturally aged mice through a transgene can delay various age-dependent deterioration in tissues and organs and extend their lifespan.

This seminal finding stimulates research to identify small molecules termed senolytic agents that can selectively kill SCs as potential therapeutics for age-related diseases. To date, several classes of senolytic agents have been identified, and most of them are natural compounds such as quercetin, fisetin, and piperlongumine. Because natural senolytic compounds have the advantages of low toxicity, they may have a better chance to be translated into clinic to treat age-related diseases or can be used as a lead for the development of more specific and potent senolytic agents.

Curcumin, a natural compound extracted from turmeric, has a broad range of biological and pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anti-cancer activities. Numerous studies suggest that curcumin has some health benefits in delaying aging and may be useful in preventing and treating age-related diseases. For example, curcumin was shown to prolong lifespan and extend healthspan in Drosophila melanogaster and Caenorhabditis elegans. To improve the bioavailability and biological activity of curcumin, many curcumin analogs were developed, including EF24, HO-3867, 2-HBA, and dimethoxycurcumin, which have been demonstrated to be more active than curcumin in preventing and treating various diseases and reducing age-dependent deterioration. However, the mechanisms of their anti-aging action have not been fully elucidated.

We hypothesized that curcumin and its analogs may increase healthspan in part by functioning as novel senolytic agents. Therefore, in this study, we examined the senolytic activity of several curcumin analogs and found that EF24 is a novel potent and broad-spectrum senolytic agent in cell culture. We show that EF24 can selectively reduce the viability of human SCs from different tissue origins and induced by different stresses. Its senolytic effect is likely attributable to the induction of apoptosis via proteasome-mediated downregulation of the Bcl-2 anti-apoptotic family proteins such as Bcl-xl. These findings provide new insights into the mechanisms by which curcumin and its analogs function as anti-aging agents and suggest that the curcumin analog EF24 has the potential to be used as a novel senolytic agent for the treatment of age-related diseases.

In connective tissue diseases such as systemic sclerosis, referred to collectively as 'fibrosis', excessive activation of connective tissue cells leads to hardening of the tissue and scarring within the affected organ. In principle, these diseases can affect any organ system and very often lead to disruption of organ function. Connective tissue cells play a key role in normal wound healing in healthy individuals. However, if the activation of connective tissue cells cannot be switched off, fibrotic diseases occur, in which an enormous amount of matrix is deposited in the tissue, leading to scarring and dysfunction of the affected tissue. Until now, scientists did not fully understand why repair processes malfunction in fibrotic diseases.

Researchers now been able to decipher a molecular mechanism responsible for the ongoing activation of connective tissue cells. In experimental studies, the researchers targeted the protein PU.1. In normal wound healing, the formation of PU.1 is inhibited by the body so that at the end of the normal healing process the connective tissue cells can return to a resting state. "We were able to show that PU.1 is activated in various connective tissue diseases in the skin, lungs, liver and kidneys. PU.1 binds to the DNA in the connective tissue cells and reprograms them, resulting in a prolonged deposition of tissue components."

PU.1 is not the only factor involved in fibrosis, as factors that are involved in the deposition of scar tissue have already been identified in the past. What has been discovered now, however, is that PU.1 plays a central role in a network of factors controlling this process. "PU.1 is like the conductor in an orchestra. If you take it out, the entire concert collapses." This approach has already been tested using an experimental drug, fuelling the hope that clinical trials on inhibiting PU.1 may soon be able to be launched, aimed at better treating fibrosis.

Resistance exercise continues to be the most effective intervention against sarcopenia. In addition, maintenance of physical activity can delay the progression of sarcopenia. Despite the strong support for maintaining an active lifestyle, adherence to physical activity guidelines remains low. The traditional therapeutic focus of sarcopenia treatment is to target growth-related pathways to increase muscle mass. Here, we discuss the positives of these strategies, but also build a case for targeting mitochondrial bioenergetics as a way to maintain muscle mass and function with age.

The vast majority of adults fail to meet physical activity guidelines. While 60% of adults, both European and American, self-report that they meet guidelines, objectively measured physical activity reveals that fewer than 10% of adults in the United States meet physical activity guidelines. Moreover, sedentary behavior alone increases the risk for sarcopenia. While there are few trials in humans on the effects of lifelong sedentary behavior, studies in mice reveal lifelong sedentary behavior impairs mitochondrial function.

It was thought that resistance exercise training had little or no effect on mitochondrial biogenesis or function. However, recent studies have shown that resistance exercise training increases mitochondrial protein fractional synthesis rates (FSRs) and improves mitochondrial function. Young adults engaged in a resistance exercise program showed increases in mitochondrial enzyme activity and respiration. While the changes in mitochondrial respiration are modest in comparison to endurance exercise, improvements in in vivo phosphocreatine recovery rates and oxidative capacity appear comparable in older adults engaged in either exercise intervention.

Aerobic exercise is generally not appreciated as a stimulator of hypertrophy; however, there is evidence that it can lead to muscle hypertrophy. Nearly half a century ago, it was first documented that aerobic exercise increases mitochondrial content. Since then, research has consistently documented that aerobic exercise improves both mitochondrial content and function. Aerobic exercise increases mitochondrial turnover since it increases both mitochondrial biogenesis (protein synthesis) and mitophagy (mitochondrial-specific autophagy). The improvement in the rate of ATP production from aerobic exercise training suggests that more energy is available to maintain proteostasis. Additionally, improvement in mitochondrial efficiency (reduction in ROS generated per oxygen consumed or ATP generated) suggests that there is less oxidative stress and damage, which would in turn improve the quality of the proteome. In all, aerobic exercise mediated improvements in mitochondrial function likely protects against sarcopenia.

Tubule repair is a common event after kidney injury, but is frequently associated with interstitial inflammation and maladaptive processes that lead to fibrosis, the hallmark of all forms of kidney disease and a reliable predictor of progression to chronic kidney disease(CKD). Recently, multiple studies identified multipotent mesenchymal stromal progenitor cells (pericytes) as the cell population that is responsible for collagen deposition after injury. Kidney fibrosis has also been correlated with arrest of tubular epithelial cells (TECs), which suggests that the epithelium plays a primary role in the progression of kidney disease. However, the factors that contribute to the cell cycle arrest are not known. Cell cycle arrest is a universal marker of cellular senescence and is evoked by a variety of stressors.

Several studies have reported a correlation between the presence of senescent cells and kidney fibrosis both during the aging process and in the context of disease, but a systematic study of cellular senescence after AKI and its potential contribution to the progression of tubular damage and fibrosis is lacking. Here, we show that in mice TECs commonly become senescent after various types of kidney injury, and that this occurs surprisingly early after injury. We show that senescent TECs express higher levels of proinflammatory factors of the SASP as a result of cell-autonomous control by the TLR/IL-1R-mediated innate immune signaling pathway, and that senescent TECs are a source of the mesenchymal progenitor-activating ligands.

Tubule-specific inhibition of TLR/IL-1R signaling by conditional inactivation of the Myd88 gene prior to senescence not only reduced the levels of epithelial cell-derived proinflammatory cytokines, interstitial infiltration, and fibrosis, but also decreased the accumulation of senescent cells and ameliorated tubular damage. Whereas inactivation soon after injury was equally effective in decreasing the number of senescent TECs, inflammation, and fibrosis, it did not protect from tubular damage. Similarly, eliminating p16+ senescent cells, but not senescent cells by FOXO4-DRI inhibitory peptide, which induces apoptosis of senescent cells by disrupting the interaction between FOXO4 and p53, reduced kidney fibrosis without reducing tubular damage.

Our results indicate that TEC senescence is a common and early event after kidney injury, and that signaling by the TLR/IL-1R pathway within the epithelium controls this phenomenon. Our findings also suggest that early intervention after injury is likely required to reduce organ damage after AKI. Furthermore, this study reveals what we believe is a novel function of the epithelial TLR/IL-R1 signaling in controlling the onset of TEC senescence in a cell-autonomous manner, consistent with the concept that the tubular epithelium triggers kidney disease following injury and also drives its progression.

People generally do not believe in the plausibility of targeting the mechanisms of aging in order to slow down and reverse age-related damage. After so many millennia of fruitless dreams, with so many powerful psychological defenses that protect our state of mind when we face the idea of inevitable death by aging, becoming hopeful is usually too much to ask. This can explain why most people, when asked about their desired lifespan, add only a few years to the life expectancy of their given countries.

However, in the last few years, things have apparently started to change. In 2015, in a study by Donner et al, it was found that given perfect mental and physical health, 797 out of 1000 participants wanted to live to 120 or longer; over half of these 797 people desired unlimited lifespans (around 40% of all participants). A new study by YouGov shows even more impressive results. We at Lifespan.io generally stay away from strong statements such as "living forever" or "immortality", because these expressions are hardly scientific and have a religious background. The notion of immortality even seems to scare some people because it seems to limit their freedom and because immortals are pictured by pop culture as criminals, crazy, or morally inferior. Therefore, people often reject the idea of extended life without perfect health.

However, in a new study by YouGov that included around 1200 participants, one in five (19%) people agreed with the statement "I want to live forever" without any promises related to perfect health. 42% of the participants chose "I want to live longer than a normal lifespan, but not forever", while 23% said, "I don't want to live longer than a normal lifespan." People in different age groups reacted to this survey differently; it turns out that the idea of radical life extension was more supported by young people (24%) than by people over 55 (13%), while support for the status quo was the opposite (19% of young people didn't want to live longer than a normal lifespan, while this position was shared by 29% of people aged 55 and older).

The YouGov survey participants were randomly selected, and few of them will be regularly exposed to news about aging and longevity research. However, over 60% explicitly expressed a desire for radical life extension. That is a big jump from the Pew Research study from 2013, where only 38% of the participants expressed the desire to undergo medical treatments to slow aging and live to be 120 or more. Of course, the questions in these surveys were formulated differently, so we cannot directly compare them. However, looking at various, similar studies, it appears that, in the last 5 years, 20% more Americans have become aware that something serious is going on in the rejuvenation biotechnology industry.

"According to Gompertz mortality law, the risk of death from all causes increases exponentially after the age of 40 and doubles approximately every 8 years. By analyzing the dynamics of disease incidence in the clinical data available from the UK Biobank, we observed that the risks of age-related diseases grow exponentially with age and double at a rate compatible with the Gompertz mortality law. This close relation between the most prevalent chronic diseases and mortality suggests that their risks could be driven by the same process, that is aging. This is why healthspan can be used as a natural proxy for investigation of the genetic factors controlling the rate of aging, the 'holy grail' target for anti-aging interventions."

To find genetic factors associated with human healthspan, the researchers studied the genomes of 300,477 British individuals. Overall, 12 genetic loci affecting healthy life expectancy were discovered. To confirm that these results hold true for other ethnicities, they used genetic data of UK Biobank participants with self-reported European, African, South Asian, Chinese and Caribbean ancestry. Of the 12 single nucleotide polymorphisms (SNPs), 11 increased risk both in discovery and in replication groups. Three of the genes affecting healthspan, HLA-DQB, LPA, and CDKN2B, were previously associated with parental longevity, a proxy for overall life expectancy.

At least three genetic loci were associated with risk of multiple diseases and healthspan at the same time and therefore could form the genetic signature of aging. HLA-DQB1 was significantly associated with COPD, diabetes, cancer, and dementia in this study and was demonstrated to be associated with parental survival earlier. The genetic variants near TYR predict death in the prospective UKB cohort and are involved in the earlier onset of macular degeneration. The chromosome 20 locus containing C20orf112 was not associated with the incidence of any of the diseases at the full-genome level, and yet was affecting the healthspan of studied individuals.

A growing body of evidence demonstrates that dietary restriction (DR) exerts its beneficial effects on brain aging at multiple levels. Although there is some degree of discrepancy across studies, likely due to the difference in the model organisms and experimental design, DR appears to mitigate all of the morphological and functional alterations in the brain associated with aging. A major hallmark of aging is systemic, low-grade chronic inflammation throughout the body, termed inflammaging. Notably, these inflammatory signs are similar to the ones associated with obesity and metabolic diseases, providing a possible glimpse into why DR exerts anti-inflammatory effects on aging-associated inflammation.

As with other organs, chronic low-grade inflammation is a common feature of the aged brain. Neuroinflammation is a host defense mechanism against harmful stimuli and damage in the brain. However, chronic inflammation can be deleterious in normal aging as well as in pathological aging related to neurodegenerative diseases. The central nervous system (CNS) is composed of heterogeneous cell types, including neurons, microglia, astrocytes, and oligodendrocytes. Although two major glial cell types, astrocytes and microglia, are known to be key players in inflammatory responses in the brain, it is now well recognized that all neural cells participate to some degree in the neuroinflammatory responses.

Neuroinflammation often manifests as astrogliosis, microgliosis, and an increase in secreted inflammatory mediators, such as cytokines, chemokines, and complement proteins. Accumulating evidence from clinical and basic research suggests that neuroinflammation is tightly connected to the decline in brain function during aging. Although the precise mechanisms of DR's neuroprotective functions are not fully elucidated, it has been suggested that DR exerts neuroprotective effects through multiple pathways, such as modulating metabolic rates, reducing oxidative stress, increasing anti-inflammatory responses, regulating insulin sensitivity, and improving synaptic plasticity and neurogenesis. All of the molecular changes induced by DR may directly or indirectly contribute to the regulation of neuroinflammation associated with aging and neurodegenerative diseases. DR may directly mitigate activation of glial cells and modulate expression of inflammatory cytokines and indirectly regulate neuroinflammation by reducing inflammatory stresses, such as accumulation of toxic proteins and oxidative stress.

Vadim Gladyshev is asking lab scientists to whip out their smartphones and take photos. Not selfies, exactly, but snapshots of their lab mice. It's a fiddly task, Gladyshev admits: mice move fast, and need to be kept still for the camera. He suggests grabbing them with one hand or taking them by the tail while they use their front paws to hold a rod. The impromptu photo shoots are all part of a crowdsourced effort to develop an algorithm that can help predict the biological age of a mouse from its mug shot - information that could help researchers studying aging understand the connection between a person's biology and how old he or she looks.

Scientists now know, for example, that people who look younger than their years tend to live longer than people whose appearance more closely matches the time they've been alive. People are surprisingly good at predicting biological age when it comes to fellow Homo sapiens. But pinpointing the biological age of mice is far more challenging. Instead, assessing the effect of anti-aging drugs in lab mice often involves taking blood samples and running expensive tests. Biomarkers such as DNA methylation signatures and analyses of metabolites and biochemical measurements consume resources and run up costs. Alternatively, researchers may need to sacrifice mice in order to examine the internal effects of a compound.

The idea for a cheap and less wasteful alternative came to Gladyshev and Alex Zhavoronkov, founder of Insilico Medicine, a company specializing in artificial intelligence (AI) for aging research and drug discovery, a couple of years ago. The pair got to chatting and came up with the idea of using a mouse's appearance as a marker of biological age - just as developers have attempted to do for humans. Mouse photo shoots have already been staged in labs across the US and Europe, and around 500 lab mice are in the catalog. The team plans to release the algorithm publicly a few months from now and allow researchers to use it for free. But the project is still in the image-collection stage, as the more reference images it has, the better the algorithm will perform. The team aims to collect images of 1,000 mice by March, but Gladyshev is planning to continue collecting until the project has sourced at least 10,000. "Future programs would tell whether one group of mice is biologically younger than another, allowing us to more easily test interventions. Instead of waiting for mice to die, they can be quickly assessed for their potential to live longer."

Inspired by British billionaire Jim Mellon, chairman of anti-aging upstart biotech venture Juvenescence, Sergey Young unveiled a 100 million fund on Monday to catalyze the development of a comprehensive solution to counteract the damaging consequences of aging. The 47-year-old considers himself a product of Peter Diamandis - the man behind the non-profit XPRIZE and venture capital fund BOLD Capital Partners - and is in charge of all things longevity at both organizations. Like Mellon, who penned Juvenescence: Investing in the Age of Longevity prior to the launch of the company Juvenescence, Young is in the embryonic stage of writing his own book designed to decode the science of aging for the masses. Meanwhile, his 100 million Longevity Vision Fund will back organizations who are working on technology to reverse the aging process and prolong healthy human life.

"We are currently working on 6 deals ... and are looking at all the usual suspects in terms of themes." These areas include early detection of serious diseases using ultrasound technology; early diagnostics for heart, cancer, and neurodegenerative diseases; stem-cell and microbiome-based therapeutics; and big data as well as AI-based applications. Unsurprisingly, Young is in dialogue with Alex Zhavoronkov's AI shop at Insilico Medicine. Zhavoronkov has deep connections in the R&D space - last year he raised funds at the behest of Shanghai high-flyer WuXi AppTec, Singapore's Temasek, Peter Diamandis, and Juvenescence.

For long-time investor and venture capitalist Young, who has insight into the aging research and development effort within the US and to a lesser extent in the UK, China and India's sizable populations pose compelling prospects for deals for his fund. "In the next decade, advancements will allow us to be a lot more predictive and preventative in the most damaging diseases. I'm thinking AI-enabled medicine will empower doctors .. technological advances to improve sleeping and meditation will emerge - and these are an essential part of a healthy, long life, along with a plant-based diet."

What initially attracted you to aging as a general discipline?

Through multiple, orthogonal, potentially synergistic interventions, we are able to extend the healthy lifespan of model organisms. In mice, the ablation of senescent cells can extend median lifespan by 30%. The augmentation of autophagy and the transient re-activation of telomerase yield similar rejuvenating effects. These interventions should be combined, as they may be synergistic. It is only a matter of time before these interventions are working in the clinic. This kind of evidence was enough for me to commit my career to geroscience because, many years ago, I saw that the 'writing is on the wall' - thanks to advances in molecular biology, healthy life extension is no longer science fiction. This century, geroscience will be a paradigm shift comparable to the antibiotics revolution in the last century.

What is the main challenge you have faced as a longevity investor?

Most geroscientists are not working on translational research. They are basic scientists. Basic science is the bedrock of everything we do, but it's not enough. Pharma has dropped the ball in drug discovery and development, and there is a major gap in the pipeline between academic proof-of-concept and drug development. There is not enough collaboration between biologists, chemists, and drug hunters. The transition through the 'valley of death' of drug development is where company-building venture capital firms such as Apollo Ventures can step in. For example, there are many biologists with data showing that gene X or protein Y, when modulated, has salutary effects. They might even identify a 'hit' molecule, such as a natural product or library compound that modulates the target or mechanism of action, but they usually don't partner with chemists to perform medicinal chemistry optimization, pharm/tox, and validation in multiple animal models of disease.

The other challenge is that, as investors, we don't see many established, aging-focused biotechs that satisfy our investment criteria. The science may be solid, but the team is lacking, or vice versa. There are not many experienced C-level biotech managers out there, and few understand geroscience. This will change once the field has a few clinical successes. Then the floodgates will open.

What can we expect from you and Apollo Ventures in 2019?

We will unveil a few more geroscience companies that are currently in stealth mode. Apollo will continue to build our internal team as well. We are looking for people with talent in both geroscience and biotech business management. Apollo was founded by a partnership of successful entrepreneurs and aging scientists with expertise in the biopharma and management consulting businesses. The depth of scientific expertise and biopharma business acumen within Apollo is unique in the geroscience space. Another distinguishing feature is that Apollo is focused more heavily on company building than other investors who are oriented toward investing in pre-established companies.

The conference was quite broad in scope and included people from the aging research community, the pharmaceutical industry, general healthcare, and the business and insurance fields. Speaking of insurance companies, it was interesting that the large insurance companies Prudential and Legal & General were both sponsoring the event; Prudential had even produced an interesting booklet for guests with the title "Prepare for 100" boldly on the cover. The book went on to talk about the changes coming to medicine and how people could soon be living longer than ever before thanks to the new medical approaches that are currently being developed.

Dr. Aubrey de Grey was in fine form as usual during the keynote panel discussion at the start of the event, just as he was when, later that day, I had the opportunity to interview him about progress with SENS. While we will be publishing the interview I did with Aubrey later, it's a good time to share the interesting concept of damage crosstalk now. It turns out that Aubrey has become more optimistic about the medical control of age-related damage and has moved his prediction of longevity escape velocity down from 20 years to 18. Quite simply, there is increasing evidence that the different aging processes have a lot more influence and interaction with each other (crosstalk) than previously thought.

Lynne Cox, a biochemist from the University of Oxford, chaired a discussion panel with Brian Delaney, president of the Age Reversal Network and who serves on our Industry Advisory Board, and Tristan Edwards, the CEO of Life Biosciences. The discussion topics were "What's at the cutting edge of aging research and development?" and "How can we accelerate research and development and the advancement of new therapies to address aging and age-related disease?" The panel was in a round table format, and attendees were also able to directly join the discussion, which proved lively and interesting. Lynne Cox, in particular, provided some very informative details about aging research.

There was considerable discussion about senescent cell clearing therapies as well as touching upon the topic of biohacking. The general feeling was that biohacking had the potential to set the field back if people conduct it in an unscientific manner and harm themselves in the process. Indeed, this echoes our sentiment that people who self-test at home should be very careful and apply a science-based approach to what they are doing. The bottom line is that if you are not recording your biomarkers and doing things scientifically, you risk hurting yourself and are taking things on faith rather than evidence; this also has potential to harm the field and set research back, so please hack responsibly.

On a more positive note, the panel was in favor about science doing something about aging and age-related diseases, and discussion of senolytics, senomorphics (therapies that block senescent cell inflammation), and cellular reprogramming were all enthusiastically discussed, especially by the academics present. This is very welcome, and it was great to see so many academics being frank about the potential of medicine to bring aging under medical control in order to prevent age-related diseases, which is in stark contrast to a decade ago, when suggesting the idea could harm your career and get you mocked by your peers. Times have certainly changed, as more and more researchers are now focusing on how we can rise to the challenge that aging presents.