Stroke Outcomes Mediated by These 2 Mechanisms

In a trending new research paper published in Aging, researchers investigated the effects of microglial activity on post-stroke inflammation and outcomes.

Stroke Outcomes Mediated by These 2 Mechanisms

The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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When the blood supply in and around the brain becomes interrupted, a stroke can occur. A hemorrhagic stroke is when a blood vessel bursts in or near the brain. An ischemic stroke is caused when a blood vessel carrying oxygen and nutrients to the brain is obstructed—usually by a clot. The most common type of stroke is ischemic, which accounts for approximately 87% of all strokes in humans. A major risk factor for an ischemic stroke is aging.

Inflammation (a chronic condition among the elderly) is a key contributing factor to strokes, and microglia are the primary immune cells in the brain. Researchers recently identified a role for the microglial IRF5-IRF4 regulatory axis in mediating responses after stroke. However, whether or not aged microglia also undergo the same regulatory mechanisms after a stroke had previously not been determined.

“Microglial activation plays a central role in initiating and perpetuating the post-stroke inflammation, and acts as a ‘double-edged’ sword to confer both detrimental and beneficial effects [9].”

In a recent study, researchers Conelius Ngwa, Abdullah Al Mamun, Shaohua Qi, Romana Sharmeen, Yan Xu, and Fudong Liu from The University of Texas Health Science Center at Houston investigated aged mice and the role of the microglial IRF5-IRF4 regulatory axis after a stroke. On August 12, 2022, their research paper was published in Aging’s Volume 14, Issue 15, and entitled, “Regulation of microglial activation in stroke in aged mice: a translational study.

The Study

“We have previously found IRF4 signaling is anti-inflammatory and IRF5 is pro-inflammatory in young ischemic microglia [11]. In the present study, we hypothesized IRF4 CKO [conditional knockout] worsens while IRF5 CKO improves stroke outcomes.” 

To better understand how microglia responds to stroke in aged individuals, the researchers first investigated microglial IRF5 and IRF4 expression in young and aged mice. A well-established mouse model of ischemic stroke was used in this study. Next, the researchers performed conditional knockout (CKO) of IRF5 or IRF4 in young and aged mice. The study arm mice underwent a 60-minute middle cerebral artery occlusion (MCAO). Stroke outcomes were quantified three days after MCAO.

To evaluate microglial activation and immune responses (surface and intracellular inflammatory markers) post-stroke, the researchers performed flow cytometry and enzyme-linked immunosorbent assay (ELISA). IRF5 CKO aged microglia had significantly lower levels of IL-1β and CD68 compared to controls. IRF4 CKO had significantly higher levels of IL-1β and TNF-α compared to control microglia. Levels of anti-inflammatory cytokines IL-4 and IL-10 were higher in IRF5 CKO, and lower in IRF4 CKO aged mice. 

“Plasma levels of TNF-α and MIP-1α were decreased in IRF5 CKO vs. flox aged mice, and IL-1β/IL-6 levels were increased in IRF4 CKO vs. controls.”

Results & Conclusion

Since IRF5 signaling drives microglial pro-inflammatory responses, the researchers hypothesized that microglial IRF5 is detrimental for aged mice in stroke. They also suggested that IRF4 signaling drives anti-inflammatory responses and its expression is protective in aged mice in stroke. Indeed, IRF5 CKO aged mice demonstrated improved stroke outcomes; whereas worse outcomes were seen in IRF4 CKO mice compared to their control counterparts. Furthermore, the results of this study demonstrated that aged microglia express higher levels of IRF5 and lower levels of IRF4 compared to young microglia after stroke.

This study provides valuable insights into how microglial activation is regulated post-stroke, and highlights the importance of the IRF5-IRF4 axis in stroke outcomes. The researchers conclude that the IRF5-IRF4 axis is a promising target for developing novel strategies to treat ischemic stroke. Further research is warranted to determine how these findings can be translated into clinical practice to improve stroke outcomes in the elderly.

“By using the aged IRF4/IRF5 microglial CKO mouse models, the study aimed to selectively suppress microglial pro-inflammatory activation and promote its anti-inflammatory response, and will potentially help develop new, effective therapeutic strategies against stroke.”

Click here to read the full research paper published by Aging.

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Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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3 Domains of Well-Being Extend Elderly Mobility and Longevity

In Aging’s Volume 14, Issue 15, cover paper, researchers hypothesized that multidimensional well-being may prolong mobility-limitation-free survival and longevity among older adults.

3 Domains of Well-Being Extend Elderly Mobility and Longevity
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The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

The word “well-being” is commonly used in workplace environments, therapy sessions, doctor’s offices, books, online, and elsewhere. However, the definition of this word seems to differ across varying contexts, cultures, traditions, values, and even biological sexes. Below are four definitions of well-being:

  • “noun: [Well-being is] the state of being comfortable, healthy, or happy.” — Oxford English Dictionary
  • “In simple terms, well-being can be described as judging life positively and feeling good.” — Centers for Disease Control and Prevention
  • “The meaning of WELL-BEING is the state of being happy, healthy, or prosperous : welfare.” — Merriam-Webster Dictionary
  • “Well-being, or wellbeing, also known as wellness, prudential value or quality of life, refers to what is intrinsically valuable relative to someone. So the well-being of a person is what is ultimately good for this person, what is in the self-interest of this person.” — Wikipedia

Based on these definitions, one could argue the root meaning of well-being may be distilled down to individual happiness and prosperity that contributes to healthy aging. However, this prosperity and happiness is not anchored to only one domain of well-being. There are three domains of being well, which include behavioralsocial and psychological well-being.

Aging & Well-Being

“Successful aging is a multidimensional construct covering behavioral, social, and psychological domains of well-being, all amenable to individual actions and public health interventions [14].”

Successful, or healthy, aging may be the result of adherence to several protective factors simultaneously within all three of the well-being domains. Previously, the majority of research on healthy aging has been limited to a single domain per study. In a new study, researchers Marguerita Saadeh, Xiaonan Hu, Serhiy Dekhtyar, Anna-Karin Welmer, Davide L. Vetrano, Weili Xu, Laura Fratiglioni, and Amaia Calderón-Larrañaga (from Karolinska InstitutetKarolinska University HospitalStockholm UniversityLund University, and Stockholm Gerontology Research Center) believe that the vast heterogeneity in aging phenotypes cannot be explained by one domain of well-being alone. On July 18, 2022, their research paper was published on the cover of Aging’s Volume 14, Issue 15, and entitled, “Profiles of behavioral, social and psychological well-being in old age and their association with mobility-limitation-free survival.”

“Despite the rising evidence supporting a multidimensional construct of successful aging, most longitudinal studies still fail to cover well-being indicators belonging to different domains, as shown by the disproportionate amount of literature focusing exclusively on lifestyle factors [4548].”

Three Domains of Well-Being: 10 Indicators

In their current study, the researchers selected 10 indicators of behavioral, social and psychological well-being: 1) Behavioral: Mediterranean diet, smoking, physical leisure activities, and mental leisure activities; 2) Social: Social leisure activities (i.e., social participation), social connections and social support; 3) Psychological: life satisfaction, negative affect and positive affect.

Blue zones” are areas around the world with high concentrations of centenarians, or people who live to be over 100 years old. A prevalent diet among people living in blue zones is the Mediterranean diet. The Mediterranean diet consists of fruits, vegetables, whole grains, beans, nuts/seeds, lean poultry, fish, seafood, dairy, eggs, and extra virgin olive oil. This diet has been closely studied as a protective factor of healthy aging.

The psychological well-being indicator listed as “negative affect” refers to the degree to which a person feels guilt, anger and fear, and the following features are considered: distressed, upset, scared, nervous, and afraid. “Positive affect” considers the extent to which a person is active, inspired, determined, alert, and enthusiastic. For additional explanations, the remaining indicators of well-being used in this study are expounded in thorough detail within the research paper itself.

Aging & Mobility

“Mobility decline precedes disability and premature death, and is therefore considered an optimal early indicator of physical function decay among older adults [34].”

The simple ability to exercise, complete day-to-day chores and maintain personal hygiene all rely on a minimum range of physical mobility. A sedentary lifestyle is a well-recognized risk factor for chronic diseases, such as obesity, type 2 diabetes, cardiovascular disease, and some forms of cancer. Furthermore, mobility limitations are associated with social isolation, depression and cognitive decline. The researchers in this study aimed to identify well-being profiles and their association with mobility-limitation-free survival.

“The specific aims of this study were: 1) to identify distinct well-being profiles among men and women separately, by using latent class analysis; 2) to determine which of these profiles are associated with the greatest benefit in terms of mobility-limitation-free survival; and 3) to quantify these potential benefits in absolute terms by calculating differences in median age at onset of mobility limitation or death across profiles.”

The Study

The study population consisted of 1488 functionally healthy individuals (after all exclusion criteria were applied to the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) population-based study). In addition to collecting self-reported data on the 10 indicators of behavioral, social and psychological well-being listed above, the researchers included data on the participants’ covariates. Covariates included age, education, number of chronic diseases, mini-Mental State Examination score (MMSE), and NEO Five-Factor Inventory (NEO-FFI) questionnaire. At the beginning of the study (baseline), the average age in the cohort was 69 years old (with a standard deviation of +/- 8.3 years). Ninety-one percent of participants had at least a high-school-level of education. Females (59%) composed the majority of the cohort.

“In this study, we used latent class analysis to detect data-driven subgroups of people with similar well-being profiles according to behavioral (diet, smoking, and physical and mental leisure activities), social (social participation, connections, and support) and psychological (life satisfaction, positive and negative affect) well-being indicators, as defined by the Centers for Disease Control and Prevention (CDC) [25].”

Since men and women tend to behave differently when it comes to multiple factors of well-being, the researchers stratified their analyses by sex. They scheduled regular followed-ups with these participants over the course of 15 years. Well-being profiles were derived from the 10 well-being indicators using latent class analysis. Endpoints were defined as mobility-limitation-free survival, limited mobility or death. Limited mobility was defined as having a walking speed below 0.8 meters per second.

“A composite endpoint, considered to be an indicator of mobility-limitation-free survival, was operationalized by taking into account the time from study entry until the development of mobility limitation (i.e., walking speed <0.8m/s) or death, whichever occurred first.”

Results

At baseline, the researchers identified three well-being profiles among both men and women that followed a clear gradient in all behavioral, social and psychological indicators throughout the study. Participants categorized in the best well-being profile had high adherence to the Mediterranean diet, the lowest proportion of current smokers, high engagement with leisure activities, and the highest levels of social and psychological well-being. Those in the intermediate well-being profile had low/moderate adherence to the Mediterranean diet, a higher proportion of former/never smokers, and moderate levels of social and psychological well-being. (Men in the  intermediate well-being profile had a low/moderate engagement in leisure activities, while women had moderate/high engagement levels.) Participants in the worst well-being profile had low adherence to the Mediterranean diet, a higher proportion of former/never smokers, the lowest levels of leisure activity engagement, and the lowest levels of social and psychological well-being.

To examine the association between these well-being profiles and the incidence of mobility limitation or death, the researchers used Cox and Laplace regression models and applied sensitivity analyses to the data.

“In agreement with the Cox regressions, results from Laplace regressions showed that men in the intermediate and best profiles survived 1 and 3 years longer without mobility limitations, respectively, compared to those in the worst profile after adjustment for potential confounders (Figure 2). Women in the intermediate and best profiles lived 2 and 3 years longer without mobility limitations, respectively, compared to those in the worst profile.”

Conclusion

The well-being profiles of older adults are associated with their risk of developing mobility limitations and death. Those in the best well-being profile had the lowest risk, while those in the worst well-being profile had the highest risk. These findings suggest that interventions to improve multi-domain well-being in older adults may improve longevity and help reduce the incidence of mobility limitations in old age. Although this study has many strengths, the researchers were forthcoming about its limitations. Future studies are recommended to confirm these findings.

“While theoretical insights into different models of successful aging are on the rise, empirical evidence from population-based longitudinal data on the complex interplay among the distinct well-being domains and their association with person-centered outcomes, such as mobility-limitation-free survival, is currently lacking. This study addresses such an important gap and provides further evidence to better understand and promote functional independence in community-dwelling older adults through primary prevention multi-domain interventions.”

Click here to read the full research paper published by Aging.

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Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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Osteoporosis Linked to Age-Related Changes in Circadian Rhythm

Researchers published a new editorial paper on restoring the circadian rhythm to minimize the risk of aging-related osteoporotic fractures.

The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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The circadian rhythm is a daily cycle (24 hours) of biological activity that is driven by an internal biological clock. A regular circadian rhythm is important for maintaining numerous facets of human life. Aging-related changes to this delicate rhythm have demonstrated negative consequences in many aspects of health, including bone health.

“Among the many risk factors for osteoporosis, a new kid on the block is disruption of the biological clock.”

On July 19, 2022, an editorial paper was published in Aging‘s Volume 14, Issue 14, entitled, “Restoring rhythm to prevent age-related fractures.” In this editorial, Annelies E. Smit, Maaike Schilperoort and Elizabeth M. Winter from Leiden University Medical Center discuss the treatment of osteoporosis by way of restoring circadian rhythm. The researchers review the use of both medical and lifestyle interventions that aim to restore circadian rhythm to minimize the risk of aging-related osteoporotic fractures.

Osteoporosis & Cortisol

Osteoporosis is a condition characterized by decreased bone mass and an increased risk of bone fracture. Age-related osteoporosis is a major public health concern, particularly in postmenopausal women. Cortisol, a stress hormone and the most important endogenous glucocorticoid (GC), plays a key role in the regulation of circadian rhythm. Circulating cortisol levels are naturally highest in the morning and gradually decline throughout the day. (This high peak in cortisol is responsible for initiating the waking cycle each morning.)

“Rhythm in circulating cortisol levels is regulated by the ‘master clock’, the suprachiasmatic nucleus (SCN) in the hypothalamus.”

Unfortunately, as humans age, SCN rhythmicity frequently becomes decoupled from environmental rhythms. Changes in circadian rhythm can result from aging-related lifestyle changes, such as changes in light exposure (which can occur from decreasing visual capabilities), the sleep-wake cycle, eating habits, and exercise patterns. Over time, cortisol begins to peak earlier in the morning, and average circulating cortisol levels increase. The researchers argue that circadian rhythm-related changes in cortisol secretion result in a loss of bone mass and age-related osteoporosis.

“Since both SCN [5] and cortisol [6] rhythm amplitude decline with age, and because we demonstrated in a preclinical model that flat endogenous GC levels result in osteoporosis, we argue that flattened circadian rhythmicity in the elderly population is causally related to the high incidence of osteoporosis at older age [4].”

Restoring Circadian Rhythm

Glucocorticoid (GC) therapy is a common treatment for osteoporosis. Unfortunately, administering glucocorticoids at an improper time can disrupt the natural circadian rhythm of cortisol secretion, leading to an increased risk of osteoporotic fractures. The researchers suggest that restoring the circadian rhythm is critical for restoring healthy patterns of cortisol secretion, especially in patients receiving glucocorticoid therapy.

“In elderly, physical inactivity and irregular eating patterns are common, and both have been demonstrated to dysregulate bone rhythm [8].”

In addition to lifestyle changes, such as timed exercise and timed feeding, the researchers note that chronotherapy may contribute to reinforcing circadian rhythmicity. Chronotherapy is a promising new field of circadian medicine that aims to optimize the timing of drug administration to match the natural circadian rhythm. The researchers suggest glucocorticoids, and any other bone formation-promoting therapeutic, should be administered in the morning (to mimic the behavior of a healthy circadian rhythm). Chronotherapy can also incorporate lifestyle interventions, such as changes in sleeping patterns, sleep hygiene and light exposure therapy.

“Thus, restoring normal sleep/wake cycles by psychological and behavioural measures, such as strict bedtime routines, may strengthen SCN rhythm.”

Conclusion

Circadian rhythms are important for bone health and preventing age-related osteoporosis. Glucocorticoid therapy can disrupt circadian rhythms, but this disruption can be minimized by administering glucocorticoids in the morning. In addition, lifestyle changes and chronotherapy can help reinforce circadian rhythms.

“In conclusion, the multifaceted origin of age-related fractures asks for a full toolbox of intervention strategies, to which restoring circadian rhythm may provide a valuable addition. Lifestyle and medical interventions may improve sleep quality and decrease risk for osteoporotic fractures (Figure 1). Furthermore, respecting circadian timing through chronotherapy could optimize current and new therapeutic outcomes.”

Figure 1. Bone health depends on diurnal variation in bone turnover, which is regulated by the circadian timing system
Figure 1. Bone health depends on diurnal variation in bone turnover, which is regulated by the circadian timing system

Click here to read the full editorial paper published by Aging.

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Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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Trending With Impact: Humanin G Treatment in AMD Reduces Inflammation

In the cover paper published in Aging-US Volume 14, Issue 10, researchers investigated a potential therapeutic intervention to reduce chronic inflammation in age-related macular degeneration (AMD).

Trending With Impact: Humanin G Treatment in AMD Reduces Inflammation

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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One of the leading causes of vision loss among aging populations in the United States, and worldwide, is age-related macular degeneration (AMD). The progression of this disease is known to be driven by inflammatory processes. However, the exact inflammation-associated proteins and the mechanisms that drive them have not yet been fully elucidated.

“Inflammation plays a crucial role in the etiology and pathogenesis of AMD (Age-related Macular Degeneration).”

In a new study in Aging (Aging-US), researchers from the University of California Irvine and the University of Southern California investigated a potential therapeutic intervention to reduce chronic inflammation in AMD and delay or prevent retinal degeneration. On May 16, 2022, this trending research paper was published on the cover of Aging’s Volume 14, Issue 10, and entitled, “Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD).”

“Our discovery is novel and may contribute to the development of therapeutics/ tools for reducing inflammation to alleviate AMD disease pathology.”

The Study

Humanin G (HNG) is a naturally produced peptide that may play a pivotal role in tissue homeostasis and normal functioning throughout the body—including the eyes. Previous studies have shown that high-intensity exercise and resistance training positively correlate with protein levels of Humanin G in human plasma and skeletal muscle. Studies have also shown that Humanin G protein levels negatively correlate with aging. In this study, researchers investigated the impact of exogenous Humanin G on markers of inflammation in AMD cells. 

“Moreover, treatment with exogenous Humanin G is known to reduce the expression of markers associated with aging-related disorders [32]. Therefore, we tested the effects of Humanin G on inflammatory markers in this study.”

First, the researchers measured levels of inflammation-associated proteins (including cell adhesion molecules, cytokines and chemokines) among samples of AMD plasma and normal (control) plasma. AMD plasma showed higher protein levels of inflammation markers compared to control plasma samples. Next, the researchers used the ELISA assay to measure Humanin G protein levels in the plasma of both AMD patients and normal subjects. They found that, in AMD patients, protein plasma levels of Humanin G were significantly lower compared to normal subjects. 

“In the current study, we found that the plasma levels of endogenous Humanin protein were significantly lower by 36.58 % in AMD patients compared to that in age-matched normal subjects.”

Exogenous Humanin G was then added to AMD and normal (control) cybrids derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and Humanin G-treated AMD and normal cybrids. Levels of inflammatory proteins were measured using the Luminex XMAP multiplex assay. The researchers observed that protein levels of inflammation markers previously elevated in AMD cells were reduced after Humanin G treatment. 

“To our knowledge, this is the first report that confirms the protective role of Humanin G against inflammation in AMD RPE transmitochondrial cybrid cells and it is significant because reducing ocular inflammation could alleviate its damaging effects observed in the RPE cells that eventually lead to retinal degeneration in AMD pathogenesis.”

Conclusion

“In conclusion, we present novel findings that: A) show reduced Humanin protein levels in AMD plasma vs. normal plasma; B) suggest the role of inflammatory markers in AMD pathogenesis, and C) highlight the positive effects of Humanin G in reducing inflammation in AMD.”

Results in this study are significant because treatment with exogenous Humanin G may be able to revert the abnormal levels of inflammatory proteins that are found in AMD patients back to (or near) normal ranges. These findings may lead to novel therapeutics that can improve AMD disease trajectory. 

“Further studies are required to gain an in-depth understanding of the mechanisms underlying Humanin G-mediated suppression of inflammation in AMD and to establish Humanin G’s therapeutic potential as an inhibitor of AMD-associated inflammation. Furthermore, in addition to administration of Humanin G, knockdown or knock-out of the studied inflammatory markers using siRNA or CRISPR editing, may present a new line of treatment for AMD.”

Click here to read the full research paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

For media inquiries, please contact media@impactjournals.com.

Trending With Impact: Neuromodulation in Alzheimer’s Disease Treatment

Dr. Fabrizio Vecchio wrote about the potential synergistic effects of neuromodulation combined with cognitive training to treat Alzheimer’s disease.

Neuromodulation in Alzheimer’s Disease Treatment

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Many neurodegenerative disorders among elderly populations share some common characteristics. In dementias, for example, neurons and glial cells undergo a progressive loss of structure or function in the brain and spinal cord. Alzheimer’s disease (AD) is the most common form of dementia and the main cause of cognitive impairment. Studies have confirmed that cognitive treatments, such as cognitive stimulation, training and rehabilitation, can improve brain function by increasing brain plasticity.

Recently, researcher Fabrizio Vecchio, from IRCCS San Raffaele Roma‘s Brain Connectivity Laboratory, discussed innovative treatment options for Alzheimer’s disease. On April 27, 2022, Dr. Vecchio published his new editorial paper in Volume 14, Issue 9, of Aging (Aging-US), entitled, “Cognitive training and neuromodulation for Alzheimer treatment.”

“Neuromodulation techniques are having a growing consensus as a therapeutic approach of incipient and mild to moderate dementia because of their capability to be modulated both in space, i.e. in different cortical and subcortical areas of the brain, and time.”

Neuromodulation

Neuromodulation is a considerably recent development in the medical field. This promising treatment option therapeutically alters nerve activity within specific neurological sites of the body using the targeted delivery of electrical stimulation or chemical agents. Neuromodulation can be used not only for patients with dementia but also for those with a number of other disorders, including chronic pain, epilepsy and psychiatric disorders. However, the demonstrated value of cognitive treatments has not been discounted by Dr. Vecchio. In his editorial paper, he discussed the potential synergistic effects of neuromodulation combined with cognitive training (COG). 

“Together with cognitive treatments one of the possible innovative strategies to be undertaken is the neuromodulation that involves non-invasive brain stimulation techniques (NIBS) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS).”

Dr. Vecchio described his recent study on repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training. In this randomized, double-blind, sham-controlled trial, researchers evaluated the efficacy of rTMS-COG treatment in Alzheimer’s patients. Before, immediately after and 40 weeks after rTMS-COG treatment, patients were assessed using neuropsychological and electroencephalography (EEG) examinations. The researchers evaluated six regions of the brain and analyzed neuropsychological and neurophysiological data derived from EEG. After six weeks of intensive daily treatment, immediate results showed an improvement in cognitive scales. At the 40-week follow-up evaluation, improvements in brain connectivity emerged.

“Based on these assumptions and promising results, particularly of rTMS and COG, some researchers hypothesized that a treatment combining rTMS and COG may result in synergic effects more effective [in] respect to applying the two therapies separately.”

Conclusion

Although more research must be conducted to confirm the clinical efficacy of neuromodulation for the treatment of Alzheimer’s disease, initial results are promising. Cognitive treatments should not be discounted either, as they have been shown to improve brain function. Dr. Vecchio suggests a potentially efficacious combination of neuromodulation and cognitive training that may offer significant benefits for patients with Alzheimer’s disease.

“In conclusion, rTMS combined with cognitive training, can be regarded as a potentially useful treatment for AD, not modifying the neuropathological changes, but slowing down their effects on brain networks and providing important groundwork for future studies to build upon. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression.”

Click here to read the full editorial paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

For media inquiries, please contact media@impactjournals.com.

Trending With Impact: Tobacco PEBP Increases Lifespan in Fruit Flies

Researchers conducted an interspecies analysis to determine the effects on aging that occur when certain plant proteins are expressed in animals and animal proteins are expressed in plants.

Fruit flies

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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The proteostasis network is a cellular quality control system that ensures proteins fold correctly, damaged proteins are eliminated and protein pools are replenished. During the aging process, the proteome and respective signaling pathways frequently become error-prone. A class of proteins believed to play a role in aging-related processes is the phosphatidylethanolamine-binding proteins (PEBPs). These conserved regulators of signaling networks are found in plants, animals and other organisms.

In a previous 2021 study, researchers from Fraunhofer Institute for Molecular Biology and Applied Ecology IME, University of Münster and Twyman Research Management demonstrated that a PEBP found in the tobacco plant, NtFT4, improves vitality, growth and protein yield when transfected in human cells. In a recent study, published in Aging (Aging-US) Volume 14, Issue 7, these same researchers transfected plant PEBPs in animals, and animal PEBPs in plants, to further investigate changes in activity within their respective aging processes. The research paper was published on April 8, 2022, and entitled, “The tobacco phosphatidylethanolamine-binding protein NtFT4 increases the lifespan of Drosophila melanogaster by interacting with the proteostasis network.”

“To investigate the functions of PEBPs in more detail, we undertook interspecies analysis and determined the molecular, cellular and organism-level effects of animal PEBPs expressed in Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) and plant PEBPs expressed in Drosophila.”

The Study

Specifically, the team used tobacco plant PEBPs (NtFT2 and NtFT4), fruit fly (Drosophila melanogaster) PEBPs (CG7054 and Pebp1) and human PEBPs (RKIP and hPEBP4). They found that the expression of animal PEBPs in the thale cress (Arabidopsis) and tobacco plants had no effect on flowering or growth. However, the expression of tobacco PEBPs in animals did have an intriguing impact. The researchers observed that the tobacco PEBP NtFT4 increased the lifespan of fruit flies by interacting with the proteostasis network—through mechanisms such as heat shock protein 26 (HSP26). NtFT4 expression in older flies promoted longevity by prolonging Hsp26 gene expression and maintaining protein integrity. After the PEBP CG7054 was knocked down in fruit flies, overall lifespan significantly decreased and approximately 20% of adult flies died within two days.

“In contrast, the expression of plant PEBPs in Drosophila increased the adult fly lifespan by up to one third, whereas the silencing of the endogenous PEBP CG7054 reduced longevity.”

Conclusion

“The heterologous expression of NtFT4 in flies revealed new aspects of PEBP activity that point to a role in proteostasis, improving health and lifespan [41].”

This study provides new insights into the role of PEBPs in plants and animals and how they might contribute to the aging process. Plants may use different cellular mechanisms than animals when it comes to aging-related processes such as the regulation of signaling networks. The results of this study highlight the unique role that plants may play in understanding the aging process. Further studies are needed to better understand the molecular mechanisms behind these effects, as well as their potential applications for aging interventions in humans.

“We found that heterologous expression of the tobacco (Nicotiana tabacum) PEBP NtFT4 in Drosophila melanogaster significantly increased the lifespan of adult flies and reduced age-related locomotor decline. Similarly, overexpression of the Drosophila ortholog CG7054 increased longevity, whereas its suppression by RNA interference had the opposite effect.”

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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Trending With Impact: Underlying Mechanisms of Replicative Senescence

Published on the cover of Aging’s Volume 14, Issue 7, researchers conducted a new study investigating the role of IGFBP5 in replicative senescence.

cell division illustration

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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In 1961, Leonard Hayflick and Paul Moorhead proposed a theory later named the Hayflick Limit. They discovered that a normal human cell can divide between 50 and 70 times before it can no longer proliferate and eventually dies. Researchers have since continued to explore this phenomenon and, today, this aging process is known as cellular (replicative) senescence.

“There are currently several experimental models of cellular senescence. Hayflick and Moorhead observed that primary human fibroblasts in culture exhibit a limited proliferative capacity [6]. This growth arrest during passages is called replicative senescence.”

This permanent cessation of the cell cycle is universally found in biology due to known and unknown causes, including the shortening of telomeres. While telomere shortening plays an important role, it is not the only event responsible for inducing cellular senescence. Thus, researchers have spent decades under the microscope experimenting with cellular models of replicative senescence.

In a new study released on April 4, 2022, researchers from Sapporo Medical University in Sapporo, Japan, investigated mechanisms of replicative senescence in vitro. Their trending research paper was published on the cover of Aging (Aging-US) Volume 14, Issue 7, and entitled, “Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts.”

The Study

Cellular senescence is typically characterized by cell growth arrest, an increase of cells positive for SA-β -gal staining, and upregulation of p16 and p19. To begin this study, the team cultured embryonic mouse fibroblasts (MEFs) and conducted cell passages according to the 3T3 method. They found that the MEFs underwent senescence after the 5th passage (P5). The team also found that at P8, the expression of insulin-like growth factor binding protein 5 (IGFBP5) mRNA was significantly reduced when compared with that of P2 MEFs.

Next, the team performed a knockdown of IGFBP5 in the MEF cells. Results showed that IGFBP5 knockdown induced premature cellular senescence in P2 MEFs. Knockdown of IGFBP5 increased phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) but did not affect expression levels of Akt or p16 repressors. The researchers also found that supplementing the cell culture growth medium with additional exogenous IGFBP5 delayed growth arrest and reduced replicative senescence in the MEF cells.

“To examine whether activated ERK1 and ERK2 by IGFBP5 knockdown are involved in the induction of senescent phenotypes, we examined effects of knockdown of ERK1 and ERK2 using a combination with IGFBP5 siRNA in P2 MEFs.”

Upon further analysis of ERK1/2’s role in IGFBP5-knockdown cells, the team found that the silencing of ERK2, and not ERK1, blocked the increase in the number of SA-β-GAL-positive cells. ERK2 knockdown attenuated the reduction in the cell number and upregulation of p16 and p21 in IGFBP5-knockdown cells. This study provides evidence that downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts.

Conclusion

For the first time, the role of IGFBP5 in replicative senescence was demonstrated in MEFs. Their findings suggest that ERK2 underlies cellular senescence induced by IGFBP5 downregulation. Cellular senescence appears to be a complex process with many moving parts. While more research is needed to fully understand the role of IGFBP5 in replicative senescence, this study provides new insights into the underlying mechanisms involved in this complex process.

“In conclusion, the results of the present study demonstrated that downregulation of IGFBP5 during serial passage contributes to replicative senescence via an ERK2-dependent mechanism (Figure 6). The results suggest that IGFBP5 counteracts replicative senescence in MEFs.”

Figure 6. Schematic summary of our findings. MEFs at early passage secrete certain levels of IGFBP5. Secreted IGFBP5 proteins inhibit MEK/ERK2 by attenuating their phosphorylation (P) in the neighboring cell, leading to suppression of cellular senescence. IGFBP5 secretion is decreased during serial passage, causing activation of ERK2 and cellular senescence.
Figure 6. Schematic summary of our findings. MEFs at early passage secrete certain levels of IGFBP5. Secreted IGFBP5 proteins inhibit MEK/ERK2 by attenuating their phosphorylation (P) in the neighboring cell, leading to suppression of cellular senescence. IGFBP5 secretion is decreased during serial passage, causing activation of ERK2 and cellular senescence.

Click here to read the full research paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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Protein Linked to Aging-Related Muscle Loss

Researchers investigated the mitochondrial protein GRSF1 for its role in the physiology of skeletal muscle aging.

Figure 1. Expression of GRSF1 across myogenesis. (A) RT-qPCR analysis of GRSF1 mRNA levels in proliferating (0 h) and differentiating (24-120 h) human myoblasts; n=3. GRSF1 mRNA levels were normalized to the levels of GAPDH mRNA. (B) Western blot analysis of the levels of GRSF1 at the indicated times during differentiation; n=2. (C) Immunofluorescence detection of GRSF1 (green) and mitochondria (red) in proliferating myoblasts and differentiating myotubes. Arrowheads indicate GRSF1 signals; n=3. Scale bar, 50 μm.
Figure 1. Expression of GRSF1 across myogenesis. (A) RT-qPCR analysis of GRSF1 mRNA levels in proliferating (0 h) and differentiating (24-120 h) human myoblasts; n=3. GRSF1 mRNA levels were normalized to the levels of GAPDH mRNA. (B) Western blot analysis of the levels of GRSF1 at the indicated times during differentiation; n=2. (C) Immunofluorescence detection of GRSF1 (green) and mitochondria (red) in proliferating myoblasts and differentiating myotubes. Arrowheads indicate GRSF1 signals; n=3. Scale bar, 50 μm.
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Skeletal muscle is responsible for regulating physical movement and comprises between 30 and 40% of the human body’s mass. The loss of skeletal muscle has major impacts on overall health and quality of life—leading to frailty and a decreased ability to perform activities of daily living. The most common cause of muscle loss is aging, and a prevalent pattern of aging-associated muscular decline is known as sarcopenia.

“With advancing age, the progressive loss of skeletal muscle mass and function, known as sarcopenia, leads to reduced muscle strength and diminishes individual mobility, quality of life, and lifespan [12].”

In a research paper published in Aging (Aging-US) Volume 13, Issue 11, researchers from the National Institutes of Health’s National Institute on Aging and Chungnam National University investigated a protein that may play a role in aging-related muscle loss. Their paper was published on June 2, 2021, and entitled, “GRSF1 deficiency in skeletal muscle reduces endurance in aged mice.”

Skeletal Muscles and Mitochondrial Proteins

The healthy operation of skeletal muscle is dependent on well-regulated mitochondrial functioning. Skeletal muscle is extremely rich in mitochondria, as mitochondria supply muscle cells with the energy they need to help move the body, known as adenosine 5′-triphosphate, or ATP. With age, the mitochondria in skeletal muscles begin to progressively malfunction. The exact mechanisms involved in this decline have not been fully elucidated.

“In aging skeletal muscle, mitochondria display reduced function, altered morphology, and increased production of reactive oxygen species (ROS), which contribute to a progressive loss of muscle mass and strength [1314].”

The guanine-rich RNA sequence binding factor 1 (GRSF1) protein is widely distributed in mammalian organs, and primarily enriched in mitochondria organelles. This makes the skeletal muscle an ideal organ in which researchers can study GRSF1, and other mitochondrial proteins, to investigate their role in aging-related processes such as sarcopenia. Although GRSF1 has been well-studied for its role in maintaining mitochondrial function, the involvement of GRSF1 in skeletal muscle aging had not yet been investigated until this study.

The Study

In this study, the researchers used Grsf1cKO mice—a mouse model in which GRSF1 is specifically knocked out in murine skeletal muscle cells. The mice appeared normal until 7-9 months of age. At 16-18 months of age, however, the researchers observed a reduction in muscle endurance compared to wild-type (WT) control mice. The authors postulated that these results suggested the loss of GRSF1 in skeletal muscle may not alter muscle function until later in life.

“The Grsf1cKO mice at this age ran about a 30% shorter treadmill distance on average relative to WT controls (Figure 3A).”

Upon further transcriptomic analysis, the team found that more than 200 muscle genes were differentially expressed in the GRSF1-deficient mice compared to the control mice. Some of the differentially expressed RNAs that were elevated in the Grsf1cKO mice were the hypoxia-inducible Mgarp mRNA, the mRNA encoding Sarcolipin (SLN), the pro-inflammatory proteins CXCL10 and NFKB2, and the transcription factor ATF3. The authors suggested that increased SLN mRNA may also potentially contribute to the decline in skeletal muscle endurance seen in Grsf1cKO mice.

“The reduction of endurance in Grsf1cKO muscle was accompanied by differential expression of several mRNAs, including some that encoded mitochondrial proteins, inflammatory proteins, ion transporters, and transcription factors (Mgarp, Sln, Cxcl10, Nfkb2, and Atf3 mRNAs).”

Conclusion

The researchers found that the absence of GRSF1 in murine skeletal muscle cells led to a decrease in muscle endurance. Initially, the researchers had anticipated that GRSF1 knock-out would lead to a dramatic loss in muscle function. However, their study revealed that the function of GRSF1 in skeletal muscle appeared to only be moderate. Overall, this is an important finding, as it provides new insights into the role of GRSF1 in muscle physiology and opens up new avenues for research into potential therapies for aging-related muscle loss.

“This modest in vivo effect suggests that there are redundant or compensatory mechanisms that prevent catastrophic damage from GRSF1 loss in aging muscle, and that identifying such factors might be of therapeutic benefit in diseases caused by impaired function of muscle mitochondria and impaired muscle regeneration.”

Click here to read the full priority research paper published in Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

For media inquiries, please contact media@impactjournals.com.

Trending With Impact: Plasma Injection Improves Poor Response to IVF

Researchers investigated the effects of injecting platelet-rich plasma in women with a poor ovarian response to in vitro fertilization (IVF).

IVF

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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In a day and age when women and men are beginning families later in the life cycle, women of advanced age (or with some health conditions) often have trouble becoming pregnant. Today, in vitro fertilization (IVF) is a widely-used form of assisted reproductive technology. This manual process of fertilization is achieved first by combining an egg and a sperm outside of the uterus and then helping the fertilized egg become implanted in the uterus.

The world’s first IVF baby was born in Lancashire, England, in 1978. Since then, this technique has solved reproductive issues for millions of women and men around the world. While this procedure has helped build many families, there is a subset of reproductively challenged women who exhibit resistance to IVF. Researchers have observed accelerated ovarian aging in women who demonstrate a poor ovarian response (POR) to IVF.

“These women are labeled ‘poor ovarian response’ (POR) or ‘poor responders’ due to a combination of low parameters of ovarian reserve and previous low oocyte yield after ovarian stimulation.”

In previous small-scale cohort and in vitro studies, exposure to platelet-rich plasma (PRP) has demonstrated improvements in ovarian tissue repair, regeneration and follicular development. In a new study, published in Aging (Aging-US) on March 22, 2022, researchers— from Acibadem Maslak HospitalAcibadem UniversityIVI RMA New JerseyThomas Jefferson University, and Yale School of Medicine—sought to validate these small-scale results by assessing the effects of intra-ovarian injection of autologous PRP in a cohort of 510 women with POR. Their trending research paper can be found in Volume 14, Issue 6, entitled, “Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP).”

The Study

This prospective observational study took place in Acibadem Maslak Hospital in Istanbul, Turkey, in 2020. The study’s inclusion criteria admitted women who were diagnosed with POR, between 30 and 45 years old, had at least a one-year history of infertility, and had at least one ovary. After the exclusion criteria were accounted for, 510 women with POR were included in the study. Patients were divided into three groups for subgroup assessment: patients younger than 38 years old, patients between 38 and 42 years old and patients between 42 and 45 years old.

Before IVF, autologous PRP was administered to participants through intra-ovarian injections. (Learn more about PRP and IVF materials and methods in the study.) The team then assessed the effects of PRP on ovarian reserve parameters and IVF outcomes. Ovarian reserve parameters included antral follicle count (AFC), ovarian volume, serum anti-Müllerian hormone (AMH) level, and serum follicle-stimulating hormone (FSH) level. IVF outcomes were defined by the number of oocytes retrieved (an oocyte is an immature ovum, or egg cell) and the number and quality of embryos that developed, including embryos in cleavage and blastocyst stages.

The Results

Compared to baseline measures before treatment, PRP injections resulted in higher AFC, higher serum AMH, lower serum FSH, and a higher number of mature oocytes and cleavage/blastocyst stage embryos. In this cohort of women with POR, the PRP intervention yielded a total pregnancy rate of 20.5% and a sustained implantation/livebirth rate of 12.9%.

“After PRP injection, 22 women (4.3%) conceived spontaneously, 14 (2.7%) were lost to follow up, and 474 (92.9%) attempted IVF. Among women who attempted IVF, 312 (65.8%) generated embryos and underwent embryo transfer, 83 (17.5%) achieved a pregnancy, and 54 (11.4%) achieved sustained implantation/live birth (SI/LB).”

The researchers found that the greatest increase in IVF outcomes was seen in women 38 years old or younger. They also performed a receiver operating characteristic curve analysis and found that the cut-off for patients who would not benefit from PRP was 40 years old. The authors explained that this was due to a lack of ovarian response.

Conclusion

The researchers suggest that PRP may be considered for IVF cycles in women with POR, especially for those younger than 38 years old. However, the authors also caution that PRP should not be recommended as part of routine treatments until further prospective randomized trials test for clinical efficacy in wider clinical applications. Intra-ovarian injection of autologous PRP may someday be the standard of care for women with POR seeking IVF.

“In conclusion, intraovarian injection of autologous PRP might be considered in women with POR. The ideal population that may benefit from this approach can be summarized as patients <40 years old, with an FSH < 21.2 mIU/mL, AMH > 0.23 ng/ml, with at least one antral follicle, and a mean ovarian volume > 4.30 cm3.”

Click here to read the full research paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

For media inquiries, please contact media@impactjournals.com.

PandaOmics Identifies Dual-Targets of Aging and Age-Related Diseases

Researchers used PandaOmics software to identify potential drug targets that could treat both aging and age-related diseases.

Researchers used PandaOmics software to identify potential drug targets that could treat both aging and age-related diseases.

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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What if drugs designed to treat conditions such as diabetes, osteoporosis and rheumatoid arthritis could at the same time provide patients with anti-aging benefits? On March 29, 2022, researchers—from Insilico MedicineUniversity of ChicagoGeorge Mason UniversityUniversity of Liverpool, and Buck Institute for Research on Aging—released a new study on the cover of Aging (Aging-US) Volume 14, Issue 6, about Insilico’s next-generation artificial intelligence (AI)-powered discovery software, called the PandaOmics platform. Their trending research paper is entitled, “Hallmarks of aging-based dual-purpose disease and age-associated targets predicted using PandaOmics AI-powered discovery engine.”

PandaOmics

The PandaOmics platform is a software based on an enormous database of research that is constantly being updated and refined. The database consists of over 1,500 diseases and 10,000 disease subtypes, approximately 1.9 trillion data points derived from over 10 million samples with microarrays, RNA sequencing, proteomes, methylomes, and other data types, 1.3 million drug compounds and biologics, and information embedded from over 40 million text-based sources and documents. This evolving omics database is then used to inform an intricate AI algorithm designed to identify patterns within the data.

The Hallmarks of Aging

While the underlying molecular mechanisms of aging are still technically in debate, researchers have basically agreed upon a consistent series of biochemical changes that have been identified in the aging process, known as the hallmarks of aging. There are nine classic hallmarks of aging, as well as three newer additions, which include: 1) altered intercellular communications, 2) cellular senescence, 3) deregulated nutrient signaling, 4) epigenetic shift, 5) genomic instability, 6) impaired proteostasis, 7) mitochondrial dysfunction, 8) stem cell exhaustion, 9) telomere attrition, 10) inflammation, 11) extracellular matrix stiffness, and 12) retrotransposons. 

Researchers have observed that substantial overlap exists between genes involved in the hallmarks of aging and in age-associated diseases (AADs). The goal of this study was to use the PandaOmics platform and the hallmarks of aging to identify dual-purpose drug targets that can be used to treat both aging and AADs.

“Hence, identifying potential targets that are implicated in multiple age-associated diseases, and also play a role in the basic biology of aging, may have substantial benefits.”

The Study

In this study, the researchers used the PandaOmics platform to generate a list of promising new or traditional aging-associated targets that may be used for drug discovery and repurposing. The team started by investigating genes that are dysregulated in multiple aging-associated diseases, as well as in aging itself. The researchers decided only to analyze 33 diseases. This decision was based on whether or not age is a strong risk factor for the disease’s onset, if there are strong confounding factors and on the availability of public datasets. Cancers and cardiovascular diseases were excluded from this list of selected diseases (this list can be found in the study).

The selected diseases were separated into AADs (n=14) and non-age-associated diseases (NAADs) (n=19). The team then programmed the PandaOmics platform to identify aging-associated patterns by prioritizing the top dysregulated genes in these diseases based on their involvement in the hallmarks of aging. The researchers compared the top-AAD and -NAAD genes and identified 145 overlapping common targets.

Results

“In this study, we used a variety of target identification and prioritization techniques offered by the AI-powered PandaOmics platform, to propose a list of promising novel aging-associated targets that may be used for drug discovery. We also propose a list of more classical targets that may be used for drug repurposing within each hallmark of aging.”

They found that most aging-associated targets were not specific to a single hallmark but were instead involved in multiple hallmarks. The team also found that most of the top targets played a role in the 10) inflammation and 11) extracellular matrix stiffness hallmarks of aging. Four targets were connected to all 12 hallmarks; these targets were AKT1, MTOR, SIRT1, and IGF1. Primary conclusions drawn from the study were that the hallmarks of aging are implicated in multiple AADs and NAADs, and that these hallmarks can be used to identify aging-associated targets for drug discovery and repurposing.

Figure 3. Targets associated with hallmarks of aging.
Figure 3. Targets associated with hallmarks of aging. 

Conclusion

The researchers were forthcoming about limitations in this study. Nevertheless, this exciting research provides valuable insight into the use of AI-powered discovery engines to uncover novel aging-associated targets for drug discovery. The PandaOmics platform is a valuable resource for aging researchers and offers the potential to identify new or traditional targets for the treatment of aging and age-related diseases.

“In conclusion, we successfully established an approach to identify potential dual-purpose targets for aging and AADs, enabling biologists and clinicians to further investigate their therapeutic potential in a cost-saving and time-efficient manner for drug discovery. These promising results underscore the ability of PandaOmics to identify novel targets not only for specific disorders, but across multiple types of diseases.”

Click here to read the full cover paper published in Aging (Aging-US).

AGING (AGING-US) VIDEOS: YouTube | LabTube | Aging-US.com

Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

For media inquiries, please contact media@impactjournals.com.

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