Lipid rafts (LRs) are microdomains (10-200 nm) with a short life, and their components, such as sphingolipids, cholesterol, and proteins, are assembled to function and disassemble quickly afterward. The components and sizes of LRs are not constant, and they can merge with each other to become larger when necessary. As hubs for signal transduction, LRs contain various signal proteins. Because signal transduction is essential for aging processes, the relationship between LRs and aging has attracted increasing attention. Aging drastically affects the components and functions of LRs. Further, considering the evidence, the influences of LRs on the hallmarks of aging are apparent. Many of these hallmarks contribute to the development of sustained inflammatory stage and aging. Hence, attempts to "cure" aging should involve amelioration of inflammaging (chronic, sterile, low-grade inflammation during aging), which can be achieved by regulating LRs.

Modulation of cholesterol is one way to regulate LRs, as cholesterol is a critical constituent of LRs. Most cellular cholesterol exists in the membrane and is enriched in LRs. Depleting cholesterol can disrupt the form of LRs and reduce the content of LRs, suggesting that cholesterol-lowering drugs such as statins, can alleviate inflammaging to anti-aging by inhibiting the formation of LRs. As expected, clinical results have demonstrated that new statin use is associated with a decreased death rate among American veterans (75 years and older).

However, one of the frequently reported adverse reactions of statins is memory impairment and cognitive decline. Coincidentally, Alzheimer's disease, which is characterized by cognitive and memory deterioration, is associated with reduced levels of cholesterol and LRs in the frontal cortex. Based on these results, we speculate that the adverse effects of statins on memory and cognitive alterations may partly be due to their cholesterol-lowering effects and hindered formation of LRs. Therefore, when using statins to delay aging, it is recommended to adopt some pharmaceutical modifications to increase the polarity of the statins or to choose hydrophilic statins instead of lipophilic statins for making them selective and inaccessible to the central nervous system, thus reducing their side effects.

Overall, aging has been proven modifiable, and some drugs for slow aging have been discovered. For example, rapamycin inhibits mTOR activation to delay aging; senolytics can target and eliminate senescent cells; sirtuin activators, which enhance sirtuin activity; Nicotinamide adenine dinucleotide (NAD) precursors that can supply cellular NAD levels; antidiabetic drugs such as metformin and acarbose; and non-steroidal anti-inflammatory drugs, can also be used. However, none of drugs target LRs to delay aging, making it a future objective. Overall, targeting LRs will be a novel strategy for prolonging life, and statins might be promising candidates for new anti-aging agents.

Most people infected with SARS-CoV-2 have a self-limiting infection and do recover; others experience more severe disease, with 10% of patients requiring intensive care unit (ICU) admission. The case-fatality rate of COVID-19 is approximately 1.5%. Most COVID-19-related deaths have occurred in those 60 years and older, and an even higher mortality was registered among the oldest old (ie, ≥80 years). The presence of a least 1 underlying chronic condition (eg, cancer, diabetes, hypertension, obesity, cardiovascular disease, cerebrovascular disease) is a major risk factor for death. Older adults are more susceptible to SARS-CoV-2 infection, more prone to develop severe COVID-19, and more frequently admitted to ICUs, with consequent increased mortality.

An extraordinary proliferation of studies suggests that SARS-CoV-2 infection unleashes an abnormal inflammatory response, the so-called cytokine storm. Indeed, severe COVID-19 in hospitalized patients is characterized by high circulating levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and lymphopenia. The abnormal inflammatory response, along with hypercoagulability and defective viral clearance, contributes to the development of severe pneumonia and acute respiratory distress syndrome (ARDS), with subsequent end-organ damage, multiorgan system failure, and eventually death. Although severe COVID-19 disproportionally affects older people, systemic inflammation during SARS-CoV-2 infection is detected in patients of all ages, including children, in whom a severe multisystem inflammatory syndrome has been described. This implies that COVID-19-induced inflammation is not per se sufficient at inducing negative health outcomes. This article provides a pathophysiologic view of COVID-19 in older adults within the frame of inflammaging, with a focus on antiinflammatory treatments for acute and postacute disease.

Aging has been identified as one of the most relevant risk factors for poor outcomes in COVID-19 disease, independently from the presence of preexisting diseases. The COVID-19 mortality risk sharply increases for elderly subjects, as showed by the reports of China, Italy, and the United States. In particular, in Italy, case fatality rate for patient aged 40 to 49 years or younger was reported of about 0.4% or lower, 1% among those aged 50 to 59 years, 3.5% in those aged 60 to 69 years, 12.8% in those aged 70 to 79 years, to 20.2% from 80 years and older.

Age is not only an important predictor for mortality, but it is also associated with higher disease severity, in terms of increased hospitalization rates, length of hospital stay, need for intensive care, and invasive mechanical ventilation. Since now, different mechanisms responsible for worse outcomes in the elderly have been suggested, which include the remodeling of immune system, the higher prevalence of malnutrition and sarcopenia, the increased burden of multimorbidity, and, to a lesser extent, the direct effects of age on the respiratory system and hormonal profile. The interplay between all these causes, rather than the individual pathophysiological mechanism, explains the increased severity of the disease with age.

Aging is the principal risk factor for many illnesses such as cancer, cardiovascular disorders, and neurodegenerative diseases like Alzheimer's disease. Therefore, most elderly are being treated for a variety of chronic diseases and are suffering from side effects of the drugs. Only a 2% hindrance in the progression of aging, comparing with treatment of a disabling illness such as cancer would end up to a 10 million rise in healthier individuals and saving a large amount of budget. Hence, identifying smart therapeutic options that uphold the process of aging on one hand and simultaneously cease or decelerate the progression of age-related illnesses is of great significance.

The mTOR inhibitor rapamycin was first identified as an antifungal metabolite. The role of mTOR signaling pathway in longevity and extend of life span has been studied in numerous species. In general, inhibition of the mTOR pathway, either genetically or pharmacologically, has shown to increase lifespan in different species. The antiaging effects of rapamycin are exerted through various mechanisms, but the main route of action of rapamycin on the aging process is through inhibition of mTOR pathway. SIRT1 and AMPK occurs following inhibition of mTOR, so rapamycin can also be indirectly effective in the aging process by activating SIRT1 and AMPK following inhibition of the mTOR pathway. As known, mortality rate from infectious diseases is higher in older ages, which may be due to reduced immune function in old ages. One of the mechanisms by which the immune system is rejuvenated is the activation of autophagy. Inhibition of mTOR pathway can increase autophagy and therefore may be effective in increasing immune function during the aging process.

Resveratrol belongs to the polyphenol family exerting medical properties. The antiaging effect of resveratrol is exerted through several mechanisms. Resveratrol mimics the effects of caloric restriction (CR) and shows positive effects of CR in the aging process. It can have antiaging effects by inducing inhibitory effects on inflammation, improving mitochondrial function, suppressing oxidative stress, and regulating apoptosis. Another antiaging mechanism of resveratrol is through the activation of SIRT1. Activation of SIRT1 increases the antioxidant capacity of tissues and improves mitochondrial function.

Metformin is a biguanide and antidiabetic for the first-line treatment of type 2 diabetes. Metformin can lower plasma glucose levels and reduce the amount of glucose absorbed by the body and the amount of glucose produced by the liver. Metformin also enhances tissue sensitivity to insulin. Antiaging effects of metformin are governed by several mechanisms. In general, metformin activates AMPK and inhibits mTOR, downregulates IGF-1 signaling, reduces insulin levels, and inhibits electron transport chain (ETC) and mitochondrial complex 1.

Lithium is an alkali metal that is present in trace amounts in the body. The antiaging effect of lithium may be related to autophagy regulation, increasing telomere length, and enhancement of mitochondrial function in the brain. Inositol monophosphatase (IMPase) and glycogen synthase kinase-3 (GSK-3) contribute to the role of lithium in the regulation of autophagy.

Spermidine is a natural polyamine that is essential for cell proliferation and growth. Spermidine, as a polycation, binds to molecules such as DNA, RNA, and lipids, so it can play an important role in cellular functions. Spermidine affects autophagy, inflammation, DNA stability, transcription, and apoptosis. According to previous studies, spermidine can cause autophagy in multiple organs such as the liver, heart, and muscles. Spermidine induces autophagy by regulating the expression of autophagy-related genes such as Atg7, Atg15, and Atg11. Increased expression of elF5A and transcription factor EB (TFEB) by spermidine also induces autophagy.

Pterostilbene is an analogue of resveratrol from blueberries, which is obtained by both natural extraction and biosynthesis. Pterostilbene has anti-inflammatory, antioxidant, and antitumor effects. In a study investing the effect of pterostilbene on sepsis-induced liver injury, it was found that pterostilbene activates SIRT1, so it can also affect FOXO1, p53, and NF-κB. Pterostilbene also decreases the levels of inflammatory cytokines such as TNF-α and IL-6, decreases myeloperoxidase (MPO) activity, and increases Bcl-2 expression. Accordingly, pterostilbene can have anti-inflammatory and antiapoptotic effects.

Melatonin is a hormone in the pineal gland that affects many physiological functions. Melatonin secretion gradually decreases with aging. One of the antiaging mechanisms of melatonin is due to its antioxidant effects and reduction of oxidative stress, which leads to improved mitochondrial function. Melatonin has the ability to scavenge toxic free radicals and decrease reactive oxygen species (ROS) and can indirectly stimulate antioxidant enzymes such as GPx, glutathione reductase (GRd), and SOD. Melatonin also exerts its antiaging effects by increasing SIRT1 expression.

Acetylsalicylic acid or aspirin is obtained from the bark of the willow tree. Aspirin has a variety of medical uses. One of the main uses is to prevent secondary cardiovascular diseases. It also has analgesic and antitumor properties. The antiaging effects of aspirin on C. elegans, mice, and Drosophila melanogaster have been investigated. Lifespan increases when germ cell progenitors become ablated. One of the proposed antiaging mechanisms of aspirin is through its effect on the reduction of germline stem cells. Another proposed mechanism is improving intestinal barrier function by restricting the K63-linked ubiquitination and preventing intestinal immune deficiency.

Fisetin is a natural compound in the category of flavonoids. Fisetin can reduce age-related decline in brain function. This action can also be due to its antioxidant and anti-inflammatory effects. Fisetin can have a direct antioxidant effect and maintain mitochondrial function in the existence of oxidative stress and increase glutathione levels in cells. It has also anti-inflammatory effects against microglial cells by inhibition of 5-lipoxygenase and decreasing the production of lipid peroxides and inflammatory products. Fisetin can prevent neuroinflammation, neurodegeneration, and memory impairment by reducing oxidative stress. These functions are mediated by preventing the accumulation of ROS, inhibiting inflammatory cytokines, and regulating endogenous antioxidant mechanisms. Fisetin has senolytic effects as well by inhibiting the PI3K/AKT pathway. Downstream molecules of the mentioned pathway are involved in different parts of cellular processes by acting on the Akt/mTOR pathway that eventually leads to elimination of senescent cells. A study in mice found that taking fisetin reduces oxidative stress and inflammation and removes senescent cells; thus, tissue homeostasis is restored and lifespan is increased.

Campisi: Many of the processes that happen during aging really happen as a consequence of the declining force of natural selection. That is, there was no natural selection for these diseases. The process we study, cellular senescence, it's now clear - and certainly in mouse models - that this process, the cellular process, drives a large number of age-related diseases, everything from macular degeneration, to Parkinson's disease, cardiovascular disease, and even late-life cancer, but it evolved to protect young organisms from cancer. So we certainly don't want to stop it when we're young.

Senescence is a state that the cell enters, in which it adopts three new traits. One of them is it gives up almost forever, almost forever, the ability to divide. It will tend to resist dying. And most important, it tends to secrete a lot of molecules that can have effects on neighboring cells, and also in the circulation. Not that many cells have been studied when they become senescent. And almost everything else we know about senescence is slowly changing as we learn more and more about different cell types and different ways that cells enter senescence.

There are still very few of them even in very old and very diseased tissue. A few percent at the most. So why do people think this has anything to do with aging? That has to do with the third thing that happens when cells become senescent is they begin to secrete a large number of molecules that have biological activity outside the cell. And that means that those senescent cells can call immune cells to the site where they are, it can cause neighboring cells to fail to function. And it basically causes a situation that is classically termed chronic inflammation.

If you eliminate senescent cells, it is possible to do one of three things to an age-related pathology: You either make it less severe, or you postpone its onset, or - and this is, of course, the one we all love - in a few cases, you can even reverse that pathology.

Dubal: in every society that records mortality across the world, women live longer than men. From Sierra Leone, where lifespan is lower, to Japan and Sweden, where lifespan is much longer. But here's a really interesting piece of information: When we look historically across multiple countries and societies, at times of extreme mortality, like famine and like epidemics, the girls will live longer than the boys and the women will live longer than the men. And this, this really suggests to us that there is a biologic underpinning for female longevity, because even when there is very high and equal stress in the environment with very high mortality, the girls are outliving the boys and the women are outliving the men. There's some very, very sad and really remarkable times that, that demonstrate this including the Irish famine and many, many other examples in our world history.

If we think about this, biologically, why there could be sex differences and human longevity. One has to do with chromosomes, our genetics, our genetic code, and every single one of our cells in our bodies. And that is that female mammals and certainly female human mammals have two X chromosomes in every cell. One of them is inactivated during development, but there are two X chromosomes, and that is the sex chromosome complement of women and girls. In contrast, boys and men have one X and one Y chromosome. And so here already at the outset, there is a very clear and striking difference in our genetics. And so with this difference, and XX in females compared to XY in males, there, there arises for biologic reasons, for sex differences in longevity. One is that in males, there's a presence of a Y. And it is thought, although not experimentally shown, that maybe there are toxic effects or deleterious effects of the presence of a Y chromosome.

Further, all the mitochondria in all of your cells are inherited from our mothers. So in the process of cellular division and the creation of a zygote, mothers pass on their mitochondria, not fathers. And so this becomes really important because mitochondria can only undergo evolution in a female body. Males will never pass their mitochondria on. And so at the end of the day, what that predicts is that mitochondrial function is more evolved to female physiology, when compared to male physiology. And this may make a difference with aging when things begin to go awry. The female cells may be more fit because their mitochondria are more evolved to the female cells compared to male cells.

The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging. Hesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging.

Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age.

Hesperetin is the first compound we have tested as a proof-of-concept for the hypothesis that a Cisd2 activator will have an anti-aging effect. Our findings provide an experimental basis for using Cisd2 as a molecular target for the screening and development of novel compounds that are able to activate Cisd2 pharmaceutically with the goal of translating these drugs into clinical interventions that can be used in geriatric medicine. Most importantly, hesperetin can be rapidly delivered systematically to multiple organs and tissues in vivo. Additionally, it has no detectable in vivo toxicity after long-term oral administration for 6-7 months in mice, specifically when supplemented in food at a dose of 100 mg/kg/day, which has a human equivalent dose of 491 mg/60 kg/day. Accordingly, it will be of great interest to develop hesperetin as a medicinally or nutritionally functional food for preventive purposes related to extending healthy lifespan and/or therapeutic purpose related to treating age-related diseases.

Some types of T cells work to calm their over-active brethren. Known as regulatory T cells, or T-regs, they typically tamp down inflammation, quieting that mob and thereby protecting nearby healthy tissues. In tumor tissue, researchers found a different flavor of T-regs. These immune-suppressing cells, swarming in tumor-environment specimens, were different from T-regs found elsewhere in the body. Their cell surfaces are marked by two distinct protein receptors. These specially marked T-regs were particularly good at tamping down inflammation, expanding in number and protecting the tumor cells from attack by other types of T cells.

To a casual observer, the T-regs from the tumor samples would look no different from those found elsewhere in the body. But the team used new techniques that allow scientists to identify characteristics of tens of thousands of individual cells in a sample, and advanced computing methods to sift through data. It allowed them to spot two types of receptor proteins on the surfaces of T-regs collected from the tumor. The telltale proteins have names only a scientist could love: IL-1R1 and ICOS. "What makes these cells unique is that they express both those proteins. You just don't see that co-expression on other T-reg cells."

One reason this pair of proteins may have been overlooked by researchers previously is that they occur in human T-regs, not in those of mice. Much of laboratory work in immunology relies on mouse models of the immune response, but this study focused on human tissues, taken from patients who either had cancer or non-cancerous lesions. Researchers hypothesize that these tumor-resident T-regs have been tricked by cancer into working for the wrong team. Surrounded by T cells searching for cancer cells to destroy, the tumors acquired an ability to either attract or generate a blanket of these ICOS/IL-1R1-bearing T-regs. Exactly how they did so is not clear, but their impact is to build up an immunosuppressive environment, protecting the tumor from ordinary T cells doing their jobs.

Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise.

One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca2+ handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.

Cancer is the uncontrolled growth of body cells leading to the formation of tumors, triggered by the accumulation of mutations in a cell's genome. In order to become malignant, metastasizing cancer, tumor cells go through a series of transformations involving interactions between the body's immune system and the tumor. However, many mechanistic details in this process are still unclear, making the prevention and treatment of cancer notoriously difficult. However, there is growing evidence that in tumor progression to metastasis, inflammation of blood vessel-lining endothelial cells is a key process.

Researchers showed that metastasizing tumors, in contrast to non-metastasizing ones, accumulate proteoglycan molecules; these, in turn, attach to and accumulate LDL to the walls of blood vessels. The bound LDL becomes oxidized. There are also high levels of its receptor, called LOX-1, in the endothelial cells of metastasizing tumors. This, they found, causes these cells to produce inflammation signals that attract neutrophils. They then proved that in mice, the suppression of LOX-1 can significantly reduce tumor malignancy, and also that LOX-1 overexpression caused an increase in signaling molecules attracting neutrophils.

The study also points to a promising approach for treating and preventing malignant cancer - and cardiovascular disease - by targeting neutrophil recruitment to endothelial cells. "The number of patients with cancer who die not of cancer, but of cardiovascular events, is increasing. Targeting the LOX-1/oxidized LDL axis might be a promising strategy for the treatment of the two diseases concomitantly."

The critical outstanding question is: Can aging processes be slowed down? Evidence in nature suggests a positive answer to this fundamental question. For instance, similar pathobiological changes associated with aging develop over very different time scales in different mammalian species. While it may take 70 years for a senile cataract to develop in a human, similar age-related changes develop in horses within 20 years, in dogs within 10 years, and in mice in even only 2 years. Analogous considerations also apply to many other age-related alterations (hair greying, muscle loss, etc.). Although the biology underlying these differences in aging rate are not well understood, these examples demonstrate that similar aging phenomena in comparable tissues can develop over very different absolute time scales. Therefore, there seems to be some plasticity that could be harnessed, in theory, for slowing down the aging process.

Much of what is currently thought to be known about the biological underpinnings of the aging process has been presented in concepts like the "hallmarks of aging" which summarize processes claimed to be involved in driving organismal aging phenomena. Here, we carefully examine the evidence presented in favor of such links between these processes and aging. As we will explain in detail below, we identify limitations that are often grounded in the choice of models and/or the way aging is measured. We conclude by outlining experimental designs that are suited to overcome these current limitations and that can be used to address if and to what extent putative aging regulators are in fact involved in regulating organismal aging rate.

Aging research essentially deals with a many-to-many mapping problem. There are changes in many age-sensitive phenotypes (collectively representing the aging process, i.e., the transition of a young adult organism to an aged one) that could, in theory, each be influenced by a large set of regulators. Advances in aging research will critically depend on a better definition of this problem. In conclusion, aging research will benefit from a better definition of how specific regulators map onto age-dependent change, considered on a phenotype-by-phenotype basis. Resolving some of these key questions will shed more light on how tractable (or intractable) the biology of aging is.

The existing literature provides evidence that acarbose can affect the life span. This review links inflammation, mitochondria, and telomeres with the gut microbiota, illustrating individual mechanisms involved in acarbose-associated life span extension. Acarbose improves the immune system, inflammatory response, and mitochondrial function by affecting the gut microbiota. Acarbose supplementation is a cost-effective method for delaying aging given its potential health-restorative effects and limited side effects. This offers hope for analyzing the use of acarbose to improve health and reduce the risk of age-related diseases.

Additional experiments should be undertaken to verify our speculations; for instance, which bacteria affect the length of telomeres and mitochondrial function after acarbose intervention needs to be studied. The role of acarbose in affecting telomere length by regulating the gut microbiota should be investigated with a more rigorous scientific approach.

The present review describes several mechanisms by which acarbose affects the life span through the gut microbiota by considering different viewpoints and provides a new theoretical basis for the mechanism of acarbose-extended life spans. Hitherto, to the best of our knowledge, no other reviews have explained the mechanisms underlying life span extension by acarbose based on the perspective of gut microbiota. In general, many factors that affect the life span and mechanisms of acarbose that can help extend the life span of humans remain to be studied.

Glutamine is a conditionally essential amino acid involved in energy production and redox homeostasis. Aging is commonly characterized by energy generation reduction and redox homeostasis dysfunction. Various aging-related diseases have been reported to be accompanied by glutamine exhaustion. Glutamine supplementation has been used as a nutritional therapy for patients and the elderly, although the mechanism by which glutamine availability affects aging remains elusive.

Here, we show that chronic glutamine deprivation induces senescence in fibroblasts and aging in Drosophila melanogaster, while glutamine supplementation protects against oxidative stress-induced cellular senescence and rescues the D-galactose-prompted progeria phenotype in mice. Intriguingly, we found that long-term glutamine deprivation activates the Akt-mTOR pathway, together with the suppression of function. However, the inhibition of the Akt-mTOR pathway effectively rescued the autophagy impairment and cellular senescence caused by glutamine deprivation.

Collectively, our study demonstrates a novel interplay between glutamine availability and the aging process. Mechanistically, long-term glutamine deprivation could evoke mammalian target of rapamycin (mTOR) pathway activation and autophagy impairment. These findings provide new insights into the connection between glutamine availability and the aging process.

To our knowledge, this cohort study is the first study examining the association between epigenetic age acceleration (EAA) and healthy longevity among older women. In this racially and ethnically diverse cohort of older women, increased EAA as measured by Horvath, Hannum, PhenoAge, and GrimAge clocks was associated with lower odds of survival to age 90 years with intact mobility. Results were similar when including intact cognitive functioning.

Among 1813 women, there were 464 women (mean age at baseline, 71.6 years) who survived to age 90 years with intact mobility and cognitive functioning, 420 women (mean age at baseline, 71.3 years) who survived to age 90 years without intact mobility and cognitive functioning, and 929 women (mean age at baseline, 70.2 years) who did not survive to age 90 years. Women who survived to age 90 years with intact mobility and cognitive function were healthier at baseline compared with women who survived without those outcomes or who did not survive to age 90 years. The odds of surviving to age 90 years with intact mobility were lower for every 1 standard deviation increase in EAA compared with those who did not survive to age 90 years as measured by Horvath (odds ratio 0.82), Hannum (odds ratio 0.67), PhenoAge (odds ratio 0.60), and GrimAge (odds ratio 0.68) clocks.

This cohort study's findings suggest that EAA may be a valid biomarker associated with healthy longevity among older women. Our results suggest that EAA may be used for risk stratification and risk estimation for future survival with intact mobility and cognitive functioning within populations. Future studies could usefully focus on the potential for public health interventions to reduce EAA and associated disease burden while increasing longevity.

In addition to neuroprotective strategies, neuroregenerative processes could provide targets for stroke recovery. However, the upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) impedes innate regenerative efforts. Here, we examine the regulatory role of PTPσ (a major proteoglycan receptor) in dampening post-stroke recovery. Use of a receptor modulatory peptide (a mimetic of the PTPσ regulatory wedge region with a TAT domain to facilitate membrane penetration) or PTPσ gene deletion leads to increased neurite outgrowth and enhanced neural stem cell migration in vitro.

Post-stroke ISP treatment results in increased axonal sprouting as well as neuroblast migration deeply into the lesion scar with a transcriptional signature reflective of repair. Lastly, peptide treatment post-stroke (initiated acutely or more chronically at 7 days) results in improved behavioral recovery in both motor and cognitive functions. Therefore, we propose that CSPGs induced by stroke play a predominant role in the regulation of neural repair and that blocking CSPG signaling pathways will lead to enhanced neurorepair and functional recovery in stroke.

Using a three-dimensional human tissue culture model mimicking the brain, researchers have shown that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer's disease. Normally HSV-1 - one of the main variants of the virus - lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function, signature features found in patients with Alzheimer's.

Researchers re-created brain-like environments in small 6 millimeter-wide donut-shaped sponges made of silk protein and collagen. They populated the sponges with neural stem cells that grow and become functional neurons capable of passing signals to each other in a network, just as they do in the brain. Some of the stem cells also form glial cells, which are typically found in the brain and help keep the neurons alive and functioning.

The researchers found that neurons grown in the brain tissue can be infected with VZV, but that alone did not lead to the formation of the signature Alzheimer's proteins tau and beta-amyloid - the components of the tangled mess of fibers and plaques that form in Alzheimer's patients' brains - and that the neurons continued to function normally. However, if the neurons already harbored quiescent HSV-1, the exposure to VZV led to a reactivation of HSV, and a dramatic increase in tau and beta-amyloid proteins, and the neuronal signals begin to slow down. "It's a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble."

Muscle strength is a powerful predictor of mortality that can quickly and inexpensively be assessed by measuring handgrip strength (HGS). What is missing for clinical practice, however, are empirically meaningful cut-off points that apply to the general population and that consider the correlation of HGS with gender and body height as well as the decline in HGS during processes of normal ageing. This study provides standardised thresholds that directly link HGS to remaining life expectancy (RLE), thus enabling practitioners to detect patients with an increased mortality risk early on.

Relying on representative observational data from the Health and Retirement Study, the HGS of 8,156 survey participants aged 50-80 years was z-standardised by gender, age and body height. We defined six HGS groups based on cut-off points in standard deviation (SD) from the mean; we use these as predictors in survival analyses with a 9-year follow-up and provide RLE by gender based on a Gompertz model for each HGS group.

Even slight negative deviations in HGS from the reference group with have substantial effects on survival. RLE among individuals aged 60 years with standardised HGS of up to -0.5 SD from the mean is 3.0/1.4 years lower for men/women than for the reference group, increasing to a difference of 4.1/2.6 years in the group with HGS of -0.5 SD to -1.0 SD from the mean. By contrast, we find no benefit of strong HGS related to survival. Survival appears to decrease at much higher levels of muscle strength than is assumed in previous literature, suggesting that medical practitioners should start to become concerned when HGS is slightly below that of the reference group.