Researchers have long suspected that the brain contains a genomic patchwork of cells harboring mutations that arose at different stages of development. These variants have even been tied to a handful of sporadic cases of neurodegenerative disease. However, due to the localized nature of these mutations throughout the brain, tracking them down, let alone investigating their involvement in disease, requires cutting-edge sequencing, cell isolation, and computational techniques. Using single-cell sequencing, a recent study estimated that each cell in the brain harbors 200-400 somatic mutations that arose during brain development, while another study reported around 1,500 per post-mitotic neuron. The mutation rate of human neurons also reportedly ramps up with age. Yet the cumulative impact of these mutations, and how many cells harbor each one, remains uncertain.

To address these questions, researchers employed ultra-deep sequencing of 56 genes linked to neurodegenerative disease in different regions from postmortem brain samples. The scientists resequenced each sample more than 1,000 times, allowing them to detect variants with high specificity and sensitivity, even for genes that are typically extremely difficult to sequence. Then, using a computational model of brain development, they used their findings to estimate the burden of somatic variation in the entire brain. In all, the researchers found 39 somatic variants among 44 of the 173 brain samples that were taken from from 54 post-mortem brains. Eight variants were in neurodegenerative disease-related genes.

The researchers next sought to extrapolate their findings to estimate the burden of variants in neurodegenerative disease-related genes across the entire brain. Using a cellular barcoding technique, they estimated they had sequenced DNA from around 611,000 cells. They were also able to estimate the proportion of cells in any given region that carried a somatic mutation in a neurodegenerative disease-related gene.

They fed this data into a statistical algorithm that simulated brain development to predict the total number and distribution of mutated cells among the estimated 86 billion in each brain. The answer: 100,000 to 1 million cells carry a somatic mutation in a disease-related gene. Incorporating information about how cells divide, differentiate, and mutate during development, the algorithm also foretold that each person likely had one large island of 10,000 to 100,000 cells that grew from one original mutation in a disease gene, while 10 percent of people had at least one island of more than 200,000 such cells. In addition, each brain contained 75 to 481 smaller islands, each consisting of just more than 100 descendants of a cell carrying a pathological variant. The researchers speculated that these islands of somatic variants trigger sporadic neurodegenerative disease, which reportedly affects roughly 10 percent of the human population.

Chronic systemic inflammation is a risk for neurodegeneration manifesting as Alzheimer's Disease (AD) and age-related cognitive decline. Markers of inflammation are associated with poorer cross-sectional cognitive performance, faster longitudinal decline in various domains of cognition as well as with structural and functional brain changes representing early markers of AD, including brain region activity, regional cortical thickness and white matter microstructural integrity. However, few studies have examined cross-sectional or longitudinal associations of inflammation with cognitive performance in a bi-racial adult cohort, and none have tested effect modification by race, age, and sex in the relationship between systemic inflammation and rate of change in cognitive performance over time while using a large battery of cognitive tests.

The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults participating in the Health Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Markers known to either increase or decrease during inflammation were tested against cross-sectional and longitudinal cognitive function, stratifying by key sociodemographic factors, including age, sex, and race.

Among key findings, a composite score combining four markers of systemic inflammation was associated with faster decline on a test of visual memory/visuo-constructive abilities, among older men only (over 50 years of age). Many other associations were detected in the expected direction for all markers except for serum iron, whereby a higher inflammatory status was linked to either worse performance at baseline or faster decline over time for specific age, sex and race groups. Most notably, baseline erythrocyte sedimentation rate (ESR) was associated with a faster decline on verbal memory among older men, whereas serum albumin was linked to slower attention decline among older men and over-time improvement in executive function in the total population. In contrast, high sensitivity C-reactive protein associations with cognition were mostly detected at baseline, for global mental status and the domain of attention.

Elevated body mass index (BMI) - a measure of weight accounting for a person's height - has been shown to be a likely causal contributor to population patterns in mortality, according to a new study. Specifically, for those in UK Biobank (a study of middle to late aged volunteers), every 5kg/m2 increase in BMI was associated with an increase of 16 per cent in the chance of death and specifically 61 per cent for those related to cardiovascular diseases.

While it is already known that severe obesity increases the relative risk of death, previous studies have produced conflicting results with some appearing to suggest a protective effect at different parts of the spectrum of body mass index. Until now, no study has used a genetic-based approach to explore this link. The findings which link body mass index and mortality, confirm that being overweight increases a person's risk of death from all causes including cardiovascular diseases and various cancers.

The team applied a method called Mendelian randomization, a technique that uses genetic variation in a person's DNA to help understand the causal relationships between risk factors and health outcomes - here mortality. This method can provide a more accurate estimate of the effect of body mass index on mortality by removing confounding factors, for example, smoking, income and physical activity, and reverse causation (where people lose weight due to ill health), which could explain the conflicting findings in previous observational studies.

Despite the known health benefits of weight loss among persons with obesity, observational studies have reported that cycles of weight loss and regain, or weight cycling, are associated with increased mortality. To study whether weight loss must be sustained to achieve health and longevity benefits, we performed a randomized controlled feeding study of weight cycling in mice.

In early adult life, obese mice were randomized to ad libitum feeding to sustain obesity, calorie restriction to achieve a "normal" or intermediate body weight, or weight cycling (repeated episodes of calorie restriction and ad libitum refeeding). Body weight, body composition, and food intake were followed longitudinally until death. A subsample of mice was collected from each group for determination of adipose cell size, serum analytes, and gene expression.

Weight loss significantly reduced adipose mass and adipocyte size in both sexes, whereas weight cycling animals regained body fat and cell size during refeeding. Sustained weight loss resulted in a dose-dependent decrease in mortality compared with ad libitum feeding. In conclusion, weight cycling significantly increased life-span relative to remaining with obesity and had a similar benefit to sustained modest weight loss.

One of the main characteristics of atherosclerosis is the accumulation of lipids in the intimal layer of the arterial wall. In atherosclerotic plaques, phagocytic cells, such as macrophages, engulf atherogenic low-density lipoprotein (LDL) particles, but are unable to process them, and thus become foam cells, having cytoplasm packed with lipid droplets. Foam cells are characterized by several typical features: they have decreased ability to migrate, while displaying enhanced production of pro-inflammatory cytokines. Therefore foam cells participate in maintaining chronic inflammation in the lesion.

Previous studies have shown several clusters of genes up- or down-regulated in macrophages in response to oxidized LDL, which is known to be atherogenic. Regarding the inflammatory response, modified LDL appeared to trigger up-regulation of genes with anti-inflammatory activities. We performed a transcriptome analysis of macrophages treated with atherogenic LDL that causes intracellular cholesterol accumulation. We used the strategy of upstream analysis for causal interpretation of the expression changes.

In this study, we discovered 27 transcription factors that were potentially responsible for the changes in gene expression induced by modified atherogenic LDL. These transcription factors were used for identifying the master-regulators (genes and proteins) responsible for regulation of large cascades of differentially expressed genes. In general, the genes that were up-regulated in response to lipid accumulation in macrophages induced by atherogenic LDL were mostly involved in inflammation and immune response, and not in cholesterol metabolism. Our results suggest a possibility that it is not cholesterol accumulation that causes an innate immunity response, but rather the immune response is a consequence of a cellular reaction to modified LDL. These results highlight the importance of the inflammatory component in the pathogenesis of atherosclerosis.

A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on altered cholesterol metabolism and inflammation. Both arms of pathogenesis involve myeloid cells. Monocytes migrating into the arterial walls interact with modified low-density lipoprotein (LDL) particles, accumulate cholesterol and convert into foam cells, which promote plaque formation and also contribute to inflammation by producing proinflammatory cytokines. A number of studies characterized transcriptomics of macrophages following interaction with modified LDL, and revealed alteration of the expression of genes responsible for inflammatory response and cholesterol metabolism. However, it is still unclear how these two processes are related to each other to contribute to atherosclerotic lesion formation.

We attempted to identify the main master regulator genes in macrophages treated with atherogenic modified LDL using a bioinformatics approach. We found that most of the identified genes were involved in inflammation, and none of them was implicated in cholesterol metabolism. Among the key identified genes were interleukin (IL)-7, IL-7 receptor, IL-15, and CXCL8. Our results indicate that activation of the inflammatory pathway is the primary response of the immune cells to modified LDL, while the lipid metabolism genes may be a secondary response triggered by inflammatory signalling.

Arguably the best available depictions of the global physiological changes produced by age are the profiles of world record performance times in swimming, athletics, and cycling, depicting the trajectory of decline in maximal integrated physiological performance capability. The curves suggest that the aging process produces a synchronized, controlled decrease in physiological performance over the human lifespan. The shape of the performance profile by age is essentially independent of discipline, distance, or phenotype. Importantly, the specific times of performance are not the driving force in the production of the shape of the declining performance profile.

We suggest that in these highly trained individuals the shape of the curve is generated by the aging process operating on a physiology optimized for any given age. We hypothesize that with adequate training this same profile and trajectory, but with lower performance times, would be generated by all individuals who engage in sufficient physical activity/exercise. Unlike performance, data obtained from examining individual physiological systems or tissues do not give information on the unceasing and changing global integrating functions of the aging process. However, these data do give valuable information about the integrity of physiological systems at a particular age and allow a direct comparison to be made between the effects of inactivity and physical activity/exercise.

Being physically active has been shown to have global protective effects on physiological systems and thus facilitates the aging process by maintaining physiological integrity. There is emerging evidence which suggests that physiological regulation of aging may be multi-compartmentalized. We do not advocate exercise as a panacea, but all the evidence indicates that being physically active and exercising is far superior to any other alternative for achieving optimal aging.

Immunosenescence is characterized by deterioration of the immune system caused by aging which induces changes to innate and adaptive immunity. Immunosenescence affects function and phenotype of immune cells, such as expression and function of receptors for immune cells which contributes to loss of immune function (chemotaxis, intracellular killing). Moreover, these alterations decrease the response to pathogens, which leads to several age-related diseases including cardiovascular disease, Alzheimer's disease, and diabetes in older individuals. Furthermore, increased risk of autoimmune disease and chronic infection is increased with an aging immune system, which is characterized by a pro-inflammatory environment, ultimately leading to accelerated biological aging.

During the last century, sedentarism rose dramatically, with a concomitant increase in certain type of cancers (such as breast cancer, colon, or prostate cancer), and autoimmune disease. Numerous studies on physical activity and immunity, with focus on special populations (i.e., people with diabetes, HIV patients) demonstrate that chronic exercise enhances immunity. However, the majority of previous work has focused on either a pathological population or healthy young adults whilst research in elderly populations is scarce. Research conducted to date has primarily focused on aerobic and resistance exercise training and its effect on immunity. This review focuses on the potential for exercise training to affect the aging immune system. The concept is that some lifestyle strategies such as high-intensity exercise training may prevent disease through the attenuation of immunosenescence.

Extracellular vesicles are matter that is released by cells. Seen for many years as not having any value, this 'cellular dust' has been studied and presents therapeutic properties similar to their mother cells, without their disadvantages: These vesicles do not divide, limiting the risk of cancer, and do not differentiate either, thus preventing the development of poor function. Furthermore, it appears that they can be produced by a single donor for several patients, and have already demonstrated their therapeutic potential in animals in repairing heart, liver and kidney lesions.

In the case of digestive fistula, in which there is abnormal communication between organs in the digestive tract or with the skin, regenerative medicine is an important therapeutic avenue to explore. Fistulas of this kind respond poorly to current treatments; they can develop following postoperative complications or an autoimmune disorder such as Crohn's disease, which causes digestive tract dysfunction.

For the first time, scientists used extracellular vesicles from stem cells to treat digestive fistula in a swine model. The study reveals that local injections into the fistula of a gel containing these vesicles results in the complete closure of post-operative digestive fistula. Researchers intend to test the new approach in a perineal fistula model found in Crohn's disease, with the hope of replacing the stem cell injections. The vesicle gel could be administered locally and easily and become a simpler, safer and more effective treatment.

We believe that increased longevity presents the biggest opportunity of the 21st century but will require a thoughtful and rapid response to ensure its benefits can be reaped. With every country in the world experiencing an ageing population, the individuals, companies and countries that best adapt will seize a substantial competitive advantage. The Longevity Forum brings together two key pillars of the longevity debate - science and society.

As science catches up with the human aspirations of living longer, a new approach to public health is urgently required. Our Juvenescence agenda advocates a new model for both health promotion and disease prevention which can support healthy longevity, increased life expectancy, improve overall productivity and ensure that healthcare spending is focused on preventing diseases of ageing rather than on curing them.

At the same time, our 100 Year Life agenda recognizes that living healthy and long lives without changes to the three stage structure of life (school, work and retirement) which has defined the 20th century, will not necessarily lead to fulfilled lives. With this in mind, we advocate a move towards a life structure which is better suited to the 21st century, with radical changes to how we approach education, careers, finances, and family life.

Tackling these issues requires a focus not on end of life but all stages of life. We need to ensure that all generations are prepared for a long and healthy life. This new era of longevity requires greater interconnection between education, financial planning, and scientific progress.

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer's disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored.

We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a non-transgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation.

In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain's natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

Alzheimer Management by Albumin Replacement (AMBAR) is an international, multicenter, randomized, blinded, and placebo controlled, parallel group clinical trial that enrolled mild and moderate Alzheimer patients from 41 treatment centers in Europe and the United States. The study was designed to evaluate the efficacy and safety of short-term plasma exchange followed by long-term plasmapheresis with infusion of Human Albumin combined with intravenous immunoglobulin in patients with mild and moderate Alzheimer's disease.

AMBAR is based on the hypothesis that most of the amyloid-beta protein - one of the proteins accumulated in the brains of Alzheimer's patients - is bound to albumin and circulates in plasma. Extracting this plasma may flush amyloid-beta peptide from the brain into the plasma, thus limiting the disease's impact on the patient's cognitive functions. Additionally, Albumin may represent a multi-modal approach to the management of the disease due to it's binding capacity, antioxidant, immune modulatory, and anti-inflammatory properties.

The AMBAR study included 496 mild and moderate Alzheimer patients, randomized in three treatment groups and one control (placebo) group. The participants were 55-85 years old and the efficacy of treatment was measured by changes in cognition and in daily living activities scores. An independent contract research organization (CRO), oversaw the trial's clinical monitoring phase and managed the data collection and analysis stages. The trial employed a randomized and double-blind design, meaning that neither patients nor evaluators knew whether subjects were receiving the treatment or the placebo.

The analysis of AMBAR data in moderate patients has shown positive, highly relevant results in a cohort of patients suffering from moderate Alzheimer's disease. In the three-combination arms the differences to placebo showed between 50 and 75% less decline for the Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog) in the treated patients and between 42 and 70% less decline for the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale. In the arm with all patients treated with plasma exchange the difference to placebo achieved a 66% less decline for the ADAS-Cog scale in the treated patients and a 52% less decline for the ADCS-ADL scale.

The metabolomic profile of aging has also been assessed in a number of species, including Drosophila melanogaster, naked mole rat, marmoset, and humans. Tissue-specific metabolomic signatures were reported to correlate with body mass and lifespan across a diverse number of species, and some tissue metabolites were found that discriminated long-lived rodents from controls. Although data on metabolomic shifts with aging and diet are rapidly accumulating, replication across studies has been limited, which has slowed progress toward ascertaining consensus hallmark candidates and signatures that define the aging metabolome across sex, strain, and species. Furthermore, to what extent these metabolomic shifts are merely a consequence of aging per se, as opposed to playing a causal role in the aging process, has been difficult to discern from what has largely been observational data.

Here, we have characterized changes in the metabolome with aging and dietary restriction (DR) using established techniques in a well-characterized hybrid rat model of aging. We have also interrogated the metabolome for shared changes in a set of human samples obtained from a cohort of younger and older subjects consuming a Western or DR diet. We report on some unique shifts in the metabolome, including alterations in glycerophospholipids, biogenic amines, and amino acids with diet and age. In addition, statistical analyses revealed that DR is a stronger driver of the circulating and tissue rat metabolomic phenotype than age.

When screening for metabolites with similar responses between species, we identified circulating sarcosine, a biogenic amine involved in methionine (Met), glycine, and folate metabolism, as decreased with aging per se in rodents and humans and increased by DR in both species. These shifts correlated with changes in rat liver glycine-N-methyltransferase (GNMT) content, which is a known sarcosine-generating enzyme. Long-lived Ames dwarf mice demonstrate significantly elevated sarcosine levels across age, while correlation analysis of metabolites following sarcosine refeeding in old rats prominently places this metabolite as an integral node linking amines, amino acids, glycerophospholipids, and sphingolipids. We also show that sarcosine feeding reduces Met levels in old animals and is a strong activator of macroautophagy in vitro and in vivo.

Taken together, these data identify sarcosine as a potentially important biomarker of diet and aging in mammals and suggest that this metabolite plays a previously unappreciated role in mediating at least some of the beneficial effects attributed to DR on proteostasis.

The idea behind the study was to test whether combinations of drugs known to extend healthspan and/or lifespan in animal models could work in synergy and produce even more pronounced effects. The team chose rifampicin, rapamycin, psora-4, metformin, and allantoin. Some of these, namely rapamycin and metformin, are well-known for their connection to lifespan, though their original purposes were somewhat different - rapamycin is used to prevent organ transplant rejection, whereas metformin is a 50-year-old, off-patent drug used to treat type 2 diabetes.

The researchers used C. elegans nematodes as test subjects; their intent was to see which drug combinations, if any, would provide the largest health and lifespan benefits without causing toxicity. While some combinations did turn out to be toxic or no more effective than the single drugs, others proved significantly more effective when used together; In particular, the combination of rapamycin, rifampicin, and allantoin achieved an 89% extension of mean lifespan, whereas rifampicin, psora-4 and allantoin resulted in a 96% increase of mean lifespan - all of which were without any toxicity.

It is also very important to note is that all treated worms of all ages didn't just live longer; rather, they spent a larger portion of their extra lifespan in good health, which constitutes even more evidence that interfering with the aging processes is a promising avenue to obtain significant health gains. Interestingly, comparable effects were observed when testing similar drug cocktails in fruit flies; nematodes and fruit flies are significantly far apart, evolutionarily speaking, which, according to the researchers, suggests that the aging mechanisms targeted by these drug combinations must trace all the way back to an ancient common ancestor of the two species. This is good news for humans, as it increases the likelihood that similar interventions might work in us as well.

Senolytics. Blood transfusions. Placenta stem cells. These are just some of the innovative ways that startups are tackling mortality and increasing the human lifespan. How can we live longer? How do we become healthy enough so that we can extend our lifespans by 5, 10, or even 50 extra years? And it's not just about living longer, but also feeling younger. For example, what if you could feel 25 at the age of 75? These are the big questions that scientists have been trying to answer for decades, with few answers.

Understanding how we age on a physiological level is an incredibly complex topic. It shares many of the cellular and molecular processes that underlie age-related diseases like cancer or Alzheimer's, which continue to elude us in their pathology. While aging itself isn't a treatable disorder or condition, companies and researchers focused on longevity are looking at bodily processes at the cellular level to see how aging progresses and trying to find the right drugs, treatments, and vitamins that might slow these processes down. And as a result, we may discover the key to longevity, or living a longer life.

For instance, a new class of drugs known as "senolytics" are now being touted as the next big thing in anti-aging research for getting rid of decrepit (but harmful) cells that stop dividing as we age, known as senescent cells. And it's not just the biotech or pharma companies looking to combat mortality with novel drug therapies. Wellness companies are developing daily supplements that claim to prolong your lifespan. And some startups are even offering blood transfusions from younger individuals for a "rejuvenating" effect.

In this report, we explore the current landscape of initiatives that aim to slow down the aging process, and in turn, reduce the likelihood of several diseases. We look at how these initiatives could promote longevity and what this market looks like for both investors and consumers.

Yesterday, we announced the successful completion of the NAD+ Mouse Project after a great fundraiser, but it seems we are not done yet. The research team at Harvard has announced a new stretch goal for the last two days of the campaign. A new 75,000 goal is to be the final step, and to support that, Dr. David Sinclair is offering to fund match the next 5000 in donations to the project to help it reach this final goal. So, for the next two days, all donations are worth double.

In our project, we will test the hypothesis that by restoring bioavailable NAD+ we can reverse aspects of the aging process. Starting with mice that are 20 months old (roughly equivalent to a 50 year old human), longer-term NMN treatments will be applied in order to restore levels of cellular NAD+ to those found in youthful mice. Your donations will not only allow us to purchase the materials necessary to perform this experiment, but also pave the way for human clinical trials aimed at showing, for the first time, that we can actually slow down human aging.

The final stretch goal will be to add even more comprehensive testing, such as end-of-life pathology (frequency and specificity of neoplasms/tumors/cancer) and MRI diagnostics (body composition, lean-to-fat ratio). This would really allow the researchers to maximize the useful data they collect during the study and help assess any changes to cancer risk, why each animal died, and what age-related diseases were affected by the drug.

New research results challenge previous findings of huge differences in life expectancy between the rich and those at the bottom of the income scale. In real life people don´t necessarily stay poor or stay rich, as assumed in previous research, and economists have now found a way to take this mobility between income-classes into account providing a more realistic way to calculate life expectancy for people from different walks of society. Their results show that in reality the difference between the lifespan of a rich and a poor person is really not that big.

In 2016 a research team showed that high-income people in the US can expect to live 6.5 years longer at age 40 than low-income individuals. The existing method assumes that the poor stay poor and the rich stay rich for the rest of their lives. In reality, however, over a ten-year period half of the poorest people actually move into groups with better incomes and likewise, half of the rich leak down into lower income classes. The mortality of those who move to a different income class is significantly different from those who stay in the same class.

When accounting for income mobility, life expectancy for a 40-year-old man in the upper income groups is 77.6 years compared with 75.2 for a man in poorer groups - a difference of 2.4 years. For women the difference between high and low-income groups is 2.2 years. However, without taking the income mobility into account the life expectancy difference was twice as big - around five years - for both men and women. Using the method, the authors suggest that the difference in the US is three years rather than 6.5.

Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated.

Aortae were harvested from young (6-month-old) and old (24-month-old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age-associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age-associated increase in the density of platelet-derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho-mothers against decapentaplegic homolog-2/3 (p-SMAD-2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age-associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet-derived growth factor.

In conclusion, CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet-derived growth factor signaling. Thus, CR reduces the platelet-derived growth factor-associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.