Fight Aging! Newsletter, November 12th 2018

Our inaugural forum, which takes place on 5 November 2018 in London, is a true public and private partnership which will address a host of issues pertaining to the full human life cycle - both from a scientific and a social science perspective. It will bring together key opinion leaders from the worlds of government, business, science and education, to identify immediate and long-term priorities for The Longevity Forum.

Life expectancy for humankind has increased considerably in the last 100 years. In fact, now we wonder about the limit of human longevity. Living better and longer is one of the main concerns of our society as well as one of the main objectives of contemporary medicine. Thus, the scientific community is working really hard to bring advances in this sense and to broaden knowledge about the genetic basis of human longevity and the biological mechanisms related to aging. Scientists want to find therapeutic strategies to prolong life and assure a quality standard. All in all, Longevity World Forum is conceived as a new space for experts to collaborate and develop knowledge about this field.

The defeat of aging lies within our collective grasp. It's time to seize this remarkable opportunity. The Eurosymposium on Healthy Ageing proclaims the possibility and the imperative of a moonshot project to overcome all age-related diseases within 25 years by tackling aging as their root cause. The result will be a world where healthcare is far less expensive; where human well-being can be radically extended; where people place greater value on the environment and on peace, in view of their expectation of much longer lives; where the right to life is more precious than ever, because life is longer.

Key steps in this initiative will include a paradigm shift stressing the need for research on aging itself, rather than only on individual diseases of old age; the removal of regulatory and other barriers which prevent or disincentivize companies from developing treatments for aging itself; an accelerated program to test anti-aging interventions on a much larger scale than anything that exists at the moment, leading to multiple human clinical trials of genuine rejuvenation biotechnologies by 2021. These programs will require a coordinated effort at national and international level, integrating diverse existing and novel research approaches. They need to be financed by both public and private organizations, and create inclusive, affordable solutions available on equal terms to everybody.

Caloric restriction (CR), also known as dietary restriction, is a simple and reproducible manipulation that delays the onset of many age-related pathophysiological changes and extends both median and maximum lifespan. The life-extending effect of CR is observed in several species, including yeast, worms and mammals; hence, CR has been widely investigated in aging research. In general, CR animals exhibit low body temperature and plasma insulin, and high plasma dehydroepiandrosterone sulfate (DHEAS). Interestingly, it has been reported that humans with this phenotype live longer than their counterparts. Furthermore, a recent report has revealed the effectiveness of CR in non-human primates, implying that CR can be also beneficial for humans.

Previous studies have suggested that the beneficial effects of CR may involve various mechanisms; for example, the suppression of growth hormone/insulin-like growth factor (GH/IGF-1) signaling, reduction of mechanistic target of rapamycin complex 1 activity, activation of sirtuin, enhancement of mitochondrial biogenesis, attenuation of oxidative and other types of stress, suppression of inflammation, and alteration of the gut microbiome. Thus, the mechanisms underpinning the effects of CR are complex and diverse, and further research is required for them to be fully elucidated.

White adipose tissue (WAT) is a major site of energy storage in the form of triglyceride (TG), but WAT has also become established as an endocrine tissue that secretes adipokines. It is accepted that the characteristics of adipocytes and their secretory profile differ according to their size. Large adipocytes storing a large amount of TG. In contrast, small adipocytes secrete more adiponectin. Moreover, small adipocytes are more sensitive to insulin and play a buffering role for whole-body lipids by absorbing them after a meal and releasing them in the fasting state. Thus, differences in the characteristics of WAT can influence whole-body metabolism.

Recent studies have demonstrated that several models of genetic modification in WAT are associated with differences in lifespan. For example, fat-specific insulin receptor knockout (FIRKO) mice display lower adiposity, enhanced mitochondrial biogenesis, and extended lifespan, compared with a control group. In addition, genetic manipulation of master regulators of adipocyte differentiation in mice is known to alter lifespan. It has also been reported that differences in adipokine secretion profiles affect lifespan. For instance, liver-specific adiponectin transgenic mice are resistant to high-calorie diet-induced obesity and demonstrate an extended lifespan.

CR prevents age-induced adiposity by lowering plasma insulin and leptin concentration and raising adiponectin concentration, while also reducing the size of adipocytes in WAT. Therefore, we hypothesized that the beneficial effects of CR may be partially mediated by functional alterations in WAT. In the process of testing this hypothesis, we identified the sterol regulatory element-binding protein 1c (SREBP-1c), a master transcriptional regulator of lipogenic gene expression, as a mediator of CR. These findings were validated by showing that CR failed to upregulate factors involved in fatty acid biosynthesis and to extend longevity in SREBP-1c knockout mice. Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of PGC-1α, a master regulator of mitochondrial biogenesis. Notably, these CR-associated phenotypes were observed only in WAT.

The muscle cells that line the blood vessels have long been known to multi-task. While their main function is pumping blood through the body, they are also involved in patching up injuries in the blood vessels. Overzealous switching of these cells from the pumping to the repair mode can lead to atherosclerosis, resulting in the formation of plaques in the blood vessels that block the blood flow. Using state-of-the art genomics technologies, an interdisciplinary team of researchers has caught a tiny number of vascular muscle cells in mouse blood vessels in the act of switching and described their molecular properties. The researchers used an innovative methodology known as single-cell RNA-sequencing, which allows them to track the activity of most genes in the genome in hundreds of individual vascular muscle cells.

"We knew that although these cells in healthy tissues look similar to each other, they are actually quite a mixed bag at the molecular level. However, when we got the results, a very small number of cells in the vessel really stood out. These cells lost the activity of typical muscle cell genes to various degrees, and instead expressed a gene called that is best known to mark stem cells, the body's master cells." Knowing the molecular profile of these unusual cells has made it possible to study their behaviour in disease. Researchers have confirmed that these cells become much more numerous in damaged blood vessels and in atherosclerotic plaques, as would be expected from switching cells. "Theoretically, seeing an increase in the numbers of switching cells in otherwise healthy vessels should raise an alarm. Likewise, knowing the molecular features of these cells may help selectively target them with specific drugs."

Vascular smooth muscle cells (VSMCs) show pronounced heterogeneity across and within vascular beds, with direct implications for their function in injury response and atherosclerosis. Here we combine single-cell transcriptomics with lineage tracing to examine VSMC heterogeneity in healthy mouse vessels. The transcriptional profiles of single VSMCs consistently reflect their region-specific developmental history and show heterogeneous expression of vascular disease-associated genes involved in inflammation, adhesion, and migration.

We detect a rare population of VSMC-lineage cells that express the multipotent progenitor marker Sca1, progressively downregulate contractile VSMC genes and upregulate genes associated with VSMC response to inflammation and growth factors. We find that Sca1 upregulation is a hallmark of VSMCs undergoing phenotypic switching in vitro and in vivo, and reveal an equivalent population of Sca1-positive VSMC-lineage cells in atherosclerotic plaques. Together, our analyses identify disease-relevant transcriptional signatures in VSMC-lineage cells in healthy blood vessels, with implications for disease susceptibility, diagnosis, and prevention.

Atherosclerotic cardiovascular disease is a build-up of cholesterol plaque in the walls of arteries, causing obstruction of blood flow. Scientists have found that high blood pressure caused by specific signalling from the brain promotes heart disease by altering stem cells within the bone marrow. The results demonstrate how an overactive sympathetic nervous system that causes elevated blood pressure can instruct bone marrow stem cells to produce more white blood cells that clog up blood vessels.

"We now know that changes in the immune system contribute significantly to heart disease. We aimed to determine how the sympathetic nervous system through the brain directly promotes atherosclerosis in the setting of hypertension. We have discovered that this form of high blood pressure, often associated with stress, causes changes within the bone marrow leading to increased white blood cells circulating though our vessels. This is significant as the general view of hypertension is that it is mainly a disease of the blood vessels, which means other heart damaging events are missed." The team is now exploring the specific molecules involved, which may shed light as to why some current therapies are ineffective.

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E deficient background. When mice were placed on a western type diet for 16 weeks we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms.

With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells, and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the β-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.

The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species.

Consistent with this, the hazard ratio for overall cancer risk per 10cm increase in human height (HR10) is about 1.1, indicating a 10% increase in cancer risk per 10cm; however, an alternative explanation invokes an indirect effect of height, with factors that increase cancer risk independently increasing adult height.

The data from four large-scale surveillance projects on 23 cancer categories were tested against quantitative predictions of the cell-number hypothesis, predictions that were accurately supported. For overall cancer risk the HR10 predicted versus observed was 1.13 versus 1.12 for women and 1.11 versus 1.09 for men, suggesting that cell number variation provides a null hypothesis for assessing height effects.

Melanoma showed an unexpectedly strong relationship to height, indicating an additional effect, perhaps due to an increasing cell division rate mediated through increasing IGF-I with height. Similarly, only about one-third of the higher incidence of non-reproductive cancers in men versus women can be explained by cell number. The cancer risks of obesity are not correlated with effects of height, consistent with different primary causation.

Whether you're looking at birds or primates or humans, the number of neurons that you find in the cortex of a species predicts around 75 percent of all of the variation in longevity across species. Body size and metabolism, in comparison, to usual standards for comparing animals, only predicted between 20-30 percent of longevity depending on species, and left many inconsistencies, like birds that live ten times longer than mammals of same size. Most importantly, humans were considered to be a "special" evolutionary oddity, with long childhood and postmenopausal periods. But this research finds that is not accurate. Humans take just as long to mature as expected of their number of cortical neurons - and live just as long as expected thereafter.

Researchers examined more than 700 warm-blooded animal species from the AnAge database which collects comprehensive longevity records. They then compared these records with data on the number of neurons in the brains of different species of animals. The researchers found that parrots and songbirds, including corvids, live systematically longer than primates of similar body mass, which in turn live longer than non-primate mammals of similar body mass. Previous studies determining what brains are made of showed that parrots and songbirds have more cortical neurons than similar-sized primates, which have more cortical neurons than any other mammal of comparable body size.

"The more cortical neurons a species has, the longer it lives - doesn't matter if it is a bird, a primate, or some other mammal, how large it is, and how fast it burns energy. It makes sense that the more neurons you have in the cortex, the longer it should take a species to reach that point where it's not only physiologically mature, but also mentally capable of being independent. The delay also gives those species with more cortical neurons more time to learn from experience, as they interact with the environment." What is the link between having more neurons in the cortex and living longer lives? That's the new big question researchers need to tackle.

The impact of obesity and overweight on the U.S. economy has eclipsed 1.7 trillion, an amount equivalent to 9.3 percent of the nation's gross domestic product, according to a new report on the role excess weight plays in the prevalence and cost of chronic diseases. The estimate includes 480.7 billion in direct health-care costs and 1.24 trillion in lost productivity, as documented in America's Obesity Crisis: The Health and Economic Impact of Excess Weight. The study draws on research that shows how overweight and obesity elevate the risk of diseases such as breast cancer, heart disease, and osteoarthritis, and estimates the cost of medical treatment and lost productivity for each disease.

For example, the treatment cost for all type 2 diabetes cases - one of the most prevalent chronic diseases connected to excess weight - was 121 billion and indirect costs were 215 billion. On an individual basis, that comes to 7,109 in treatment costs per patient and 12,633 in productivity costs. America's Obesity Crisis assesses the role excess weight plays in the prevalence of 23 chronic diseases and the economic consequences that result. To mention a few, obesity and overweight are linked to 75 percent of osteoarthritis cases, 64 percent of type 2 diabetes cases, and 73 percent of kidney disease cases. "Despite the billions spent each year on public health programs and consumer weight-loss products, the situation isn't improving. A new approach is needed."

As our ability to affect the aging processes has been dramatically improved within the past decade, now is an excellent time for rationalists to consider new evidence regarding the necessity and feasibility of rejuvenation biotechnology. The amount of harm caused by aging is immense from a human standpoint. It is, by far, the greatest threat to living people today, even in the most violent of countries. (It has long since dethroned the previous all-time killer, infectious disease, which we did something about.) In a world with untreated aging, everyone who does not die of something else will suffer from decades of declining health. Death is the inevitable result.

Aging is a global tragedy from an economic standpoint as well. Aging is the largest driver of healthcare costs in the United States. As birthrates remain low and unhealthy lifespans remain relatively long, the proportion of the economy devoted to taking care of older people can only increase. This economic burden represents an enormous expenditure of human labor, as large amounts of money and time are spent on keeping people alive as their bodies slowly fail them.

Fifteen years ago, the idea of intervening against aging through rejuvenation biotechnology was widely considered unfeasible or outside of human ability; today, it is mainstream science. The Hallmarks of Aging is one of the most frequently cited papers in biology. A wide variety of researchers at prestigious universities are actively involved in pursuing rejuvenation biotechnology therapies. Multiple biotechnology companies are developing interventions against the Hallmarks of Aging, each one of which has at least one partial intervention currently in development. For any given person, it is possible that partial interventions may delay enough of the aging processes long enough for further interventions to allow for more healthy years of life, until, ultimately, a comprehensive suite of therapies is developed to control all of the aging processes. This concept is called longevity escape velocity.

Unfortunately, aging is an enormous problem, not just in terms of the harms it does but in the number of specific therapies that will need to be successfully developed in order to completely control it. The current amount of effort is significant but not enough to bring about the medical control of aging as soon as would otherwise be possible. As a rationalist, you know better than to suffer from the bystander effect, waiting for someone else to do what needs doing. If you have the aptitude and are entering college, consider becoming a researcher yourself. Alternatively, you can aid advocacy efforts, fund research efforts, or, if you are an investor, finance the development of rejuvenation biotechnology companies.

From the standpoint of heart health, the Tsimane are a model group. A population indigenous to the Bolivian Amazon, the Tsimane demonstrate next to no heart disease. They have minimal hypertension, low prevalence of obesity, and their cholesterol levels are relatively healthy. And those factors don't seem to change with age. Also minimal is the incidence of type 2 diabetes. Researchers have now conducted the first systematic study that examines what the Tsimane consume on a regular basis and compares it to that of the Moseten, a neighboring population with similar language and ancestry, but whose eating habits and lifeways are more impacted by outside forces.

Using the same measurement strategy employed by the U.S. Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, the researchers interviewed 1,299 Tsimane and 229 Moseten multiple times about everything they had eaten or drunk in the previous 24 hours. Using published and their own nutritional estimates for all items, and a variety of methods to estimate portion size, they provided a detailed breakdown of daily food intake. The high-calorie (2,433-2,738 kcal/day) Tsimane diet was characterized by high carbohydrate and protein intake, and low fat intake (64, 21 and 15 percent of the diet, respectively). In addition, the Tsimane don't eat a wide variety of foods, relative to the average U.S. or Moseten diet. Almost two-thirds of their calories are derived from complex carbohydrates, particularly plantains and rice. Another 16 percent comes from over 40 species of fish, and 6 percent from wild game. Only 8 percent of the diet came from markets.

Despite the low dietary diversity, the researchers found little evidence of micronutrient deficiencies in the Tsimane's daily intake. Calcium and a few vitamins (D, E and K) were in short supply, but the intake of potassium, magnesium, and selenium - often linked to cardiovascular health - far exceeded U.S. levels. Dietary fiber intake was almost double U.S. and Moseten levels. The conclusion: A high-energy diet rich in complex carbohydrates is associated with low cardiovascular disease risk, at least when coupled with a physically active lifestyle (Tsimane adults average 17,000 or so steps per day, compared to Americans' 5,100). Moving away from a diet that is high in fiber and low in fat, salt, and processed sugar represents a serious health risk for transitioning populations.

The use of model organisms in aging research has been essential to achieve a key milestone in the field: the aging process can be modulated. Instead of just a passive, undefined decline of physiological functions, aging has turned out to be the result of a complex interconnection of genetic and biochemical mechanisms that have recently been categorized in 9 molecular hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Although we are still far from understanding how this intricate network of pathways inexorably coordinates organismal deterioration, in vivo studies in animal models have proven that single genetic manipulations can extend lifespan or ameliorate certain age-related phenotypes. Also, external interventions, that is, caloric restriction, which target specific pathways, have demonstrated that aging can be delayed in a variety of species.

For several years, the use of invertebrate animal models-such as the worm Caenorhabditis elegans or the fruit-fly Drosophila melanogaster-has led aging research by providing the first insights into those molecular pathways that are determinant in the aging process and for lifespan extension. Despite the great progress achieved by using simple model organisms carrying mutations in specific genes, increasing efforts have been made during recent years to address whether these fundamental mechanisms are also shared by mammalian systems. In this regard, mouse models have become an excellent tool in aging research because of their relative short lifespan (which allows the monitoring of the aging process in a reasonable window frame) and to the feasibility of performing genetic manipulations. Also, mice share many of the age-related phenotypes found in human subjects, including the increased risk to develop certain diseases with age, such as cancer. Nevertheless, those age-related pathologies frequently found in elderly humans and absent in aged mice, such as certain cardiovascular (ie, atherosclerosis) or neurodegenerative (ie, Alzheimer's) diseases, can be studied using the appropriate genetically modified mouse model already created to mimic these common human disorders. Accordingly, in this review, we revisit the hallmarks of aging through the prism of those biological insights provided exclusively by gain- and loss-of-function mouse models.

We have focused on those genetic interventions that have a direct impact on a specific hallmark and discuss how this manipulation affects the aging process. Of note, the pleiotropic function of certain genes together with the inherent interconnection of some hallmarks makes sometimes difficult to point at a single molecular pathway/hallmark once a gene has been deleted or overexpressed. Finally, we have primarily highlighted those genetically engineered mice that shorten or increase healthy lifespan, keeping in mind that certain features of mouse models showing accelerated aging are not present in normal aging and vice versa. We have found examples of existing animal models for the majority of hallmarks of aging. However, this analysis has also surfaced some weaknesses and many challenges ahead.

The Longevity Leaders Conference is about both the science of longevity and the business of longevity. Its purpose is to connect the thought leaders, key opinion leaders, CEOs, innovators, and disruptors from the world of life sciences, technology, financial services, government and the investment community to discuss how the grand challenges of Longevity can be tackled, how the significant opportunities can be seized, and to forge the partnerships and relationships to succeed in this new age.

The themes in focus include: The future of the science of ageing, accelerating research and development to enable the eradication of age-related disease and cracking the code to treat ageing as a unitary disease. The future of care: what are the new business models and partnerships needed to support assisted living, the care homes of the future, domiciliary care, chronic care management and end of life care? Realising the potential of the longevity industry revolution: what are the business model innovations in research and development, care, consumer and financial services necessary to ensure success? Derisking longevity: how can companies and pension funds derisk from longevity? What are the best new ideas to manage longevity risk? The technology challenge: realising the potential of new connected and digital health possibilities and the power of artificial intelligence and blockchain to enhance and extend human health lifespans. The investment opportunity: how can investors reap the longevity dividend?

Revolutionary new developments in geroscience and biotechnology, the advent of personalised, precision, and preventative medicine and other disruptive technologies are all converging and conspiring to mean that extending lifespan and healthspan beyond 100 years will soon become the norm. There can be no doubt that the age of longevity is upon us, and it is up to us to tackle its grand challenges - from eradicating age-related disease, and perhaps ageing itself, to redefining the future of care, reimagining retirement living, derisking longevity in financial service industries and developing the commercial and business models that will lead to prosperity in this new age. Those who invest and develop the technology, products and solutions to meet these challenge stand to reap incredible dividends of the multi-trillion longevity industry that will disrupt traditional working norms, challenge virtually all businesses and transform society's structure.

To live successfully and independently, older adults need to be able to manage two different levels of life skills: basic daily care and basic housekeeping activities. People 85-years-old and older form the fastest-growing age group in our society and are at higher risk for becoming less able to perform these life skills. For this reason, researchers are seeking ways to help older adults stay independent for longer. Recently, a research team focused their attention on learning whether eating more protein could contribute to helping people maintain independence.

Protein is known to slow the loss of muscle mass. Having enough muscle mass can help preserve the ability to perform daily activities and prevent disability. Older adults tend to have a lower protein intake than younger adults due to poorer health, reduced physical activity, and changes in the mouth and teeth. To learn more about protein intake and disability in older adults, the research team used data from the Newcastle 85+ Study. This study's researchers approached all people turning 85 in 2006 in two cities in the UK for participation. At the beginning of the study in 2006-2007, there were 722 participants, 60 percent of whom were women. The participants provided researchers with information about what they ate every day, their body weight and height measurements, their overall health assessment (including any level of disability), and their medical records.

The researchers learned that more than one-quarter (28 percent) of very old adults had protein intakes below the recommended dietary allowance. The researchers noted that older adults who have more chronic health conditions may also have different protein requirements. To learn more about the health benefits of adequate protein intake in older adults, the researchers examined the impact of protein intake on the increase of disability over five years. The researchers' theory was that eating more protein would be associated with slower disability development in very old adults, depending on their muscle mass and muscle strength. As it turned out, they were correct. Participants who ate more protein at the beginning of the study were less likely to become disabled when compared to people who ate less protein.

Flies eating a Spartan diet are protected from leaky gut and the systemic inflammation associated with it as they age. Conversely, flies on a rich diet are more prone to developing intestinal permeability, a condition linked to a variety of human conditions including inflammatory bowel disease. Researchers have shown that gaps in the intestinal barrier are caused by an age-related increase in the death of intestinal epithelial cells, also known as enterocytes.

The researchers zeroed in on dMyc, a gene involved in cell proliferation. They observed that levels of dMyc act as a barometer of cellular fitness in enterocytes, post-mitotic intestinal cells. They found that cells that have too little dMyc get eliminated by neighboring cells through a process termed cell competition in an attempt to maintain gut health. Levels of dMyc naturally decline with age in enterocytes, leading to excessive cell loss and thus a leaky gut. This decline in dMyc was enhanced by a rich diet, while dietary restriction maintained dMyc level in the flies, preventing leaky gut and extending the lifespan of the animals.

The researchers also looked at the role of dysbiosis, an imbalance in the intestinal bacteria or microbiome of the flies, as a potential contributor to leaky gut. Even though dysbiosis has been proposed as a leading cause of leaky gut, researchers found that removing intestinal bacteria with antibiotics conferred only minimal protection to the animals and did not prevent age-related damage to enterocytes. "The intestinal epithelium is affected by everything that moves through the gut. It would make sense that diet would have major impact on the health of those cells, especially over a lifetime of eating. While we understand the interest in the role of the microbiome, we think that diet may ultimately be the primary driver in cellular changes leading to leaky gut."

With age, our tissues lose their function and capacity to regenerate after being damaged. The main conclusion drawn from recent findings is that these fibroblasts lose their cell identity, as if they had "forgotten" what they are, and consequently their activity is altered, thus affecting tissue. The new study reveals the cellular and molecular pathways affected by ageing and proposes that they could be manipulated to delay or even reverse the skin ageing process.

Dermal fibroblasts are key for the production of collagen and other proteins that make up the dermis and that preserve the skin's function as a barrier. The activity of these cells is also crucial for the repair of skin damage. As we age, the dermis loses its capacity to produce collagen, and consequently its capacity to repair wounds is also significantly impaired. A single-cell analysis confirmed the loss of fibroblast identity in aged animals. Using sophisticated computational tools, scientists observed that aged fibroblasts show a less defined molecular conformation compared to young fibroblasts and come to resemble the undefined cell states observed in newborn animals.

"The elderly face many problems in this regard because their skin does not heal properly and its barrier properties are decreased, thus increasing the risk of skin infections and systemic infections. The notion that the loss of cell identity is one of the underlying causes of ageing is interesting and one that we believe hasn't been considered before."