In this recent study, researchers compared three IGF-1 polymorphisms in postmenopausal Asian women and investigated their potential link to osteoporosis.
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Osteoporosis is characterized by the loss of bone density and an increased risk of fractures. This serious health condition is a major public health concern, particularly among older women. According to the National Osteoporosis Foundation, approximately 80% of the estimated 10 million Americans with osteoporosis are women. Additionally, roughly one in two women over the age of 50 will break a bone due to osteoporosis.
“Osteoporosis (OP) is prevalent in postmenopausal women. Several studies investigated the association between IGF-1 polymorphisms and OP among postmenopausal females with conflicting outcomes.”
While the main risk factor for osteoporosis is undeniably aging, the causes of osteoporosis are more complex—involving a combination of genetic and environmental factors. The insulin-like growth factor 1 (IGF-1) gene plays a critical role in bone growth and development, and previous studies have suggested that variations in this gene may be associated with osteoporosis. Some genetic variants have been found to be associated with decreased IGF-1 levels, which may contribute to the development of osteoporosis.
“Although two meta-analyses have been published, conclusion of the association between IGF-1 and OP is pending, probably due to limited studies on postmenopausal women [21, 22].”
The Study
To further investigate the association between IGF-1 variants, osteoporosis and postmenopausal women, the researchers conducted a case-control study involving a cohort of postmenopausal women in Taiwan. The study included a total of 95 women with osteoporosis and 222 age-matched controls without this condition. The researchers genotyped the participants for the three IGF-1 variants and analyzed the data to determine the association between these variants and osteoporosis.
The results of the study revealed an association between the rs35767 variant and osteoporosis in these postmenopausal Asian women. Women with the variant had an increased risk of osteoporosis compared to those without the variant. In addition to the case-control study, the researchers also conducted a meta-analysis to combine the results of previous studies on the topic. This meta-analysis included their current findings and three other studies (published in English), totaling 2,267 individuals. The meta-analysis confirmed the results of their case-control study and found a significant association between the rs35767 variant and risk of osteoporosis in postmenopausal Asian women.
“We reveal a conclusive risk association in rs35767 with OP in postmenopausal females judged by TSA with 2,267 Asians in a combination of 3 published studies and our case-control study. However, rs2288377 and rs5742612 show no association with OP but it needs more sample sizes to evaluate the relationship.”
Conclusion
In conclusion, this research paper provides strong evidence for a decisive association between the rs35767 variant in the IGF-1 gene and the development of osteoporosis in postmenopausal Asian women. The study suggests that this variant may be a significant genetic risk factor for osteoporosis in this population. Their research could help in understanding the genetic basis of osteoporosis and also pave the way for personalized medicine in the management of this condition in the future. Identifying individuals at high risk for osteoporosis based on their genetic profile could allow for early detection and interventions to prevent or delay the onset of this disease. However, more research is needed to confirm these findings in other populations and to compare this study with other studies that have not been documented in the English language.
“To conclude, our case-control study is a crucial sample in meta-analysis to reach [the] conclusion of the association between IGF-1 rs35767 and OP in postmenopausal women.”
Click here to read the full research paper published by Aging.
Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.
In this new study, researchers aimed to further elucidate the mechanisms of sarcopenia by examining the influence of denervation in young and middle-aged mice.
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A hallmark characteristic of aging is the progressive loss of skeletal muscle mass, known as sarcopenia. A process called motor neuron denervation (Den)—when nerve signals to muscles are blocked or reduced—leads to muscle atrophy, fatigue and eventually muscle loss. Determining how and when Den events influence older muscles is crucially important for developing interventions to stop or reverse age-related muscle wasting.
“Further, aged muscle exhibits reduced plasticity to both enhanced and suppressed contractile activity. It remains unclear when the onset of this blunted response occurs, and how middle-aged muscle adapts to denervation.”
Dysfunctional mitochondria in muscle tissue are known to increase with age. Lysosomes are responsible for the recycling of damaged mitochondria. However, as muscles age, lysosomal function in muscle tissue also declines.
“The purpose of this study was to compare mitochondrial turnover pathways in young (Y, ~5months) and middle-aged (MA, ~15months) mice, and determine the influence of Den.”
Male mt-Keima mice aged 4-6 months (young) and 14-16 months (middle-aged) were included in this study. The researchers performed surgical procedures to induce Den in the hindlimb muscles of the study mice. After one, three, or seven days of Den, tissue was excised and imaged using confocal microscopy. The researchers collected whole-muscle protein extracts and conducted Western blotting. Statistical analysis was performed using the data they collected.
The middle-aged muscles were compared to muscles from control and young mice. The researchers found that muscle mass, mitochondrial content and PGC-1α protein levels were not different between the young and middle-aged mice. However, indications of enhanced mitochondrial fission and mitophagy and a greater abundance of lysosome proteins were evident in the middle-aged muscle. Their data suggest that increases in fission drive an acceleration of mitophagy in middle-aged murine muscle in order to preserve mitochondrial quality.
“Den exacerbates the aging phenotype by reducing biogenesis in the absence of a change in mitophagy, perhaps limited by lysosomal capacity, leading to an accumulation of dysfunctional mitochondria with an age-related loss of neuromuscular innervation.”
Conclusion
“In our present study, the inability to upregulate mitophagy flux with denervation is driven by a combination of 1) failure to increase mitophagic proteins and 2) the appearance of dysfunctional lysosomes.”
This latest study may shed light on how muscles age and reveal the importance of mitophagy and lysosomal function in maintaining healthy muscles among middle-aged mice. The study also highlights that denervation induces mitochondrial decline and exacerbates lysosome dysfunction in muscles, thereby worsening age-related muscular atrophy. Further studies are needed to gain a deeper understanding of the mechanisms behind these changes and how they can be prevented or reversed.
“Thus, therapies to combat muscle wasting with age-related physiologic denervation must be designed accordingly. Our results imply targeting both mitochondrial biogenesis and maintenance of lysosome capacity will serve to restore mitochondrial homeostasis and likely metabolic capacity of skeletal muscle.”
Click here to read the full research paper published by Aging.
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In a new study, researchers explored Alzheimer’s disease and its potential relationship with the estrogen receptor-α gene (ESR1).
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The United States government currently has a mind-blowing annual budget of $3.5 billion designated for Alzheimer’s disease (AD) and dementia research funding. Therapeutics pushed forward thus far have been largely based on the amyloid-beta (Aβ) cascade hypothesis of AD. Surprisingly, despite decades and billions, these interventions have yielded little to no benefits for AD patients. This lack of efficacy has encouraged some researchers to rethink AD pathology and focus on discovering key triggers and mechanisms of neuroinflammation.
“There has been a lengthy and ongoing scientific debate around the causative factors of AD, and the relative importance of both senile Aβ plaques and tau tangles has been largely informed by postmortem investigations of the AD brain. For several decades, the amyloid hypothesis has dominated the field, which has brought forth many high-profile therapeutic attempts that have produced side effects but no real benefits [5].”
Women & Alzheimer’s Disease
Women compose two-thirds of the United States Alzheimer’s population. Is this gender-specific risk a result of living longer or is it due to other causes, perhaps related to hormonal differences or gender-associated differential gene expression? Previous studies have found that estrogen may protect neurons from the damaging effects of amyloid-beta plaques and tau tangles. However, in women, estrogen levels tend to decline with age, which could be one reason why aging women are more susceptible to AD.
“AD is characterized by three major questions: Why is age the primary risk factor? Why are women more sensitive to the onset of this form of dementia? And why are neurons in areas of the brain that are essential for memory selectively targeted?”
The Study
Originally, the researchers in this study had been in the process of investigating ESR1-knockdown in breast cancer when they stumbled upon another discovery. (ESR1 is a gene that codes for the estrogen receptor, a protein that helps to regulate cell division and differentiation.) To their surprise, KEGG pathway enrichment analysis showed that ESR1 may also be related to axonal guidance, inflammation-related gene markers and Notch signaling pathways. Upon further validation using a dataset of in vivo AD inflammatory samples, the team found that the ESR1 gene was altered in AD patients and was associated with an increase in pro-inflammatory markers.
“ESR dysfunction likely plays a role in AD pathology – especially in women – although the specific mechanisms remain unclear. In vivo and ex vivo studies demonstrate that neuroinflammatory brain states overlap with ESR signaling pathways and that these two systems interact closely.”
In the current study, the researchers used an animal model to explore the potential role of ESR1 in modulating inflammation-related AD pathology. Using a macrophage cell line, they identified ESR1 as a key modulator of inflammation in the context of AD. They then showed that when the ESR1 gene was absent or mutated, neuroinflammation occurred. This finding offers a potential mechanism for understanding the gender-specific risk of AD in women.
“Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1β, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalized treatment of AD.”
Conclusion
The research team concluded that further studies are needed to elucidate the exact mechanisms through which ESR1 modulates inflammation and its role in Alzheimer’s disease. These findings may offer a novel therapeutic direction for treating AD. Therapeutics targeting ESR1 could potentially be used to reduce inflammation in the brain and prevent AD progression. This may be beneficial for both men and women afflicted with this devastating disease.
“Unfortunately, despite enormous efforts, there remains no cure for this terrible illness, and current treatments merely alleviate its devastating symptoms for a short time. This study performed several bioinformatics-based analyses, concluding that ESR1 dysfunction might mediate axonal guidance, induce neuroinflammation or pyroptosis in the brain, and subsequently worsen AD conditions.”
Click here to read the full research paper published by Aging.
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.
Researchers evaluated three different mouse strains with varying sensitivity to radiation lung fibrosis in an effort to uncover the underlying mechanisms.
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Radiation is an effective treatment for many types of cancer. Unfortunately, this treatment has the potential to cause long-term side effects in some patients, including the thickening or scarring of lung tissue, known as pulmonary fibrosis. Radiation-induced pulmonary fibrosis (RIPF) is a serious complication that can occur after radiation therapy and can lead to death. Predicting an individual’s risk of developing RIPF remains challenging for clinicians, as little is known about the underlying mechanisms that cause it.
“Differential susceptibility to lung injury from radiation and other toxic insults across mouse strains is well described but poorly understood.”
While the precise mechanisms underlying RIPF are not fully understood, it is thought that senescent pneumocytes (or alveolar cells) play a key role. Pneumocytes are a type of cell in the lung that are essential for gas exchange. Type II pneumocytes (AECII) function as alveolar stem cells after lung injury. The researchers hypothesized that macrophages (a type of white blood cell that play an important role in immune responses) may contribute to promoting AECII senescence.
“AECII are known to be in close contact with alveolar macrophages, and, in this fashion, to contribute to lung homeostasis [11].”
The researchers hypothesized that natural variations in macrophage function contribute to differences in RIPF susceptibility. To explore their hypothesis, they evaluated three different mouse strains with varying sensitivity to radiation lung fibrosis: C57L mice (RIPF-prone), C57BL6/J mice (intermediate) and C3H/HeN mice (RIPF-resistant). Female mice (to avoid sex-based differences in results) underwent thoracic irradiation (IR). Changes in macrophages and pneumocytes were assessed.
The Results
The team found that susceptibility to radiation-induced lung injury and premature AECII senescence varied by mouse strain. Pulmonary irradiation led to varied macrophage phenotypes and accumulation in each strain. In responses to polarizing stimuli, macrophages demonstrated strain-dependent responses. M2 macrophages induced AECII senescence via NOX2-derived superoxide production in a strain-dependent manner. Finally, macrophages expressing NOX2 accumulated in fibrotic lungs after radiation.
“NOX1 and NOX2 protein were expressed at the highest levels in C57L BMDM, with intermediate expression in C57BL6/J BMDM and the lowest expression in C3H/HeN BMDM (Figure 6B).”
The researchers demonstrated that the C57L mice (the strain with the greatest sensitivity to RIPF) exhibited the greatest rate of accumulation of senescent AECII cells. At the same time, they found that the fibrosis-sensitive (C57L and C57Bl6/J) mouse strains exhibit a greater accumulation of M2 polarized macrophages than the fibrosis-resistant strain (C3H/HeN).
“However, until now, the impact of M2 polarization on AECII senescence was unexplored. In this study, we identified that M2 macrophage polarization can contribute to AECII senescence, potentially leading to a positive feedback loop that furthers pulmonary injury.”
Conclusion
This study provides new insights into the role of macrophages in RIPF susceptibility. The findings suggest that natural variations in macrophage function contribute to differences in RIPF susceptibility. The different macrophage polarization profiles across strains may contribute to their varying susceptibilities to RIPF by promoting AECII senescence. These findings may help to develop new strategies for the prevention and treatment of RIPF.
“In this study, variation in the accumulation of senescent cells across strains with varying sensitivity to fibrosis has been established. Further, strain variation in macrophage response to polarizing stimuli and capacity to produce superoxide and induce senescence in epithelial cells is described. Together, these data highlight the importance of macrophage-epithelial interactions in the context of lung fibrosis and identify NOX2 as a possible therapeutic target in radiation lung injury.”
Click here to read the full research paper published by Aging.
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.
Researchers investigated the relationship between familial longevity, chronological age and heart rate parameters, including heart rate variability and 24-h rhythms.
Closeup view of an ECG/EKG display
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A normal resting heart rate (HR) for adults should be anywhere between 60 and 100 beats per minute. A low resting heart rate has been associated with better overall health and fitness. Crosswise, a higher resting heart rate appears to have a strong correlation with mortality. Heart rate variability (HRV), the beat-to-beat changes in heart rate, is indicative of the heart’s ability to respond to changes in physical and emotional stress. Low HRV has been shown to be a risk factor for heart disease, while high HRV has been associated with good heart health. Although HR and HRV are frequently studied, these parameters are not often investigated continuously or over long periods of time in healthy, middle-aged individuals.
“Parameters of HR and HRV are often investigated during a short electrocardiogram (ECG) measurement at the study center or in the hospital, but not continuously over a longer period while individuals continue with their daily lives.”
“This is one of the first studies to look at the relationship between parameters of HR, HRV, and 24-h rhythms in HR based on continuous ambulatory ECG measurements over a period of several days with both familial longevity and chronological age in a single design.”
The majority of the recruited study participants were middle-aged and from the Leiden Longevity Study (LLS): 37 offspring of long-lived families between 52 and 83 years old, and 36 of their partners/spouses of the same age range. In addition, the researchers recruited 35 younger individuals from the Switchbox Leiden Study between 18 and 40 years old. All study participants were asked to wear a small heart rate monitor, the Equivital EQ02 life monitor (EQ02), for 24 to 90 hours. They were then instructed to carry on with their daily lives and regular routines.
Results & Conclusion
After data cleaning and statistical analyses, no association between heart rate parameters and familial longevity was found. However, middle-aged participants had lower 24-hour heart rates (average and maximum HR, not minimum HR), lower amplitudes, and earlier trough and peak times than the young participants. During long-term EQ02 recordings, middle-aged participants showed a less optimal HRV in both the sleep and awake periods. The researchers believe this might indicate that older hearts are less adaptable than those in the young.
“This could be a first indication of deteriorated cardiovascular health in middle-aged individuals.”
The researchers were forthcoming about the limitations of this study. The study sample was relatively small, there was no standardization of daily activities among the participants, and any potential medications used by the younger participants were not adjusted for (as they were for the middle-aged participants). Despite these limitations, this study provides novel insight into heart rate parameters over longer periods of time and in relation to familial longevity and chronological age.
“In our study, we can conclude that resting HR during the sleep period is not associated with familial longevity or chronological age. This study showed that continuous ambulatory ECG measurements can be used to obtain adequate information on HR, HRV and 24-h rhythms in HR, which was also showed by others [50]. However, the small sample size, due to the poor quality of a part of the data, is a limitation of this study and should be improved in future studies. Furthermore, we suggest for future research to control for exercise and day planning between groups. Lastly we suggest to include an additional group with participants of an older age than the middle-aged group, and to investigate the relation between health status and HR parameters.”
Click here to read the full research paper published by Aging.
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.
In a trending new study, researchers investigated the efficacy of an adenoviral-based COVID-19 vaccine in elderly patients.
Adenoviral COVID-19 Vaccine Elicits Robust Immunity in Elderly Cohort
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Around the world, more than 180 COVID-19 vaccines are currently in production or development. Some COVID-19 vaccines have been less effective in the elderly—a population that is already highly vulnerable to severe viral infection. Humoral immunity, or antibody-mediated immunity, is an important weapon against COVID-19. Immune responses in the elderly are often hindered by aging, an unfortunate process known as age-related immunosenescence. Vaccines that can successfully elicit a robust humoral immune response in the elderly are critical for achieving COVID-19 immunity and interrupting disease transmission in this population.
“The development of an effective vaccine against SARS-CoV-2 targeted for an elder population is a challenge [17]. Furthermore, there is limited data describing the behavior of COVID-19 vaccines when administered to the elderly.”
Sputnik V
The two most widely available vaccines in the United States are both mRNA vaccines, the Pfizer-BioNTech and Moderna vaccines. Of course, there are other vaccines that are more commonly available in other countries, such as Gam-COVID-Vac, or Sputnik V. Sputnik V is an adenoviral-based SARS-CoV-2 vaccine.
“Gam-COVID-Vac (Sputnik V), uses a heterologous recombinant adenovirus 26 (Ad26) and adenovirus 5 (Ad5) as vectors that deliver the genetic sequence of the SARS-CoV-2 Spike protein, has been administered to tens of millions of volunteers worldwide, and has a good tolerability profile [14, 15].”
Adenoviral-based vaccines use a weakened form of a common cold virus (adenovirus) to deliver the genetic instructions for making the SARS-CoV-2 spike protein. When these instructions are delivered to human cells, they cause the cells to produce the spike protein. The body then produces antibodies against the spike protein, which provides immunity against SARS-CoV-2. In early 2021, Sputnik V was the only vaccine available to the elderly in Argentina. The ability of this particular vaccine to elicit humoral immunity in this elderly population had yet to be fully investigated.
In this study, 149 volunteers between 70 and 96 years old received two doses of the Sputnik V vaccine between December 2020 and February 2021. The researchers took blood samples from the participants before vaccination and 14, 28, 90, and 180 days post-vaccination (dpv). The researchers used the blood samples to analyze the humoral immune responses (antibodies) that were elicited by Sputnik V.
Results & Conclusion
The results showed that Sputnik V elicited robust anti-RBD immune responses in the elderly volunteers. The researchers found that the younger participants and the participants with previous COVID-19 infection had higher anti-RBD immune responses. They also found that humoral immune responses did not vary by gender at early time points. However, concentrations of antibodies were more persistent in elderly females than males at 60 dpv, and only dropped at 90 dpv.
“Our results show that Gam-COVID-Vac was able to deal with the ageing of the immune system, eliciting a robust immune response in an elderly cohort, which lasted approximately 90 dpv at high levels, and protected against COVID-19.”
Immunization with Sputnik V may be a promising vaccine for the prevention of severe COVID-19 disease in elderly patients. This suggests that adenoviral-based vaccines could be a safe and effective option for protecting elderly patients against COVID-19 and other emerging infectious diseases. However, additional studies are needed to further evaluate the safety profile and efficacy of this vaccine in elderly patients. If this vaccine proves to be effective in preventing COVID-19 in the elderly, it could have a profound impact on public health.
“As the aging population is increasing globally, especially in developed countries, vaccine efforts must consider age-related issues in order to ensure effectiveness. Ongoing studies will provide data regarding the best strategy to strengthen and prolong the protective immune response against COVID-19 in the elder population, challenging the immunosenescence process, to ameliorate the severity of the disease and avoid the SARS-CoV-2 infection.”
Click here to read the full research paper published by Aging.
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.
In a trending new study, researchers investigated a common chemical and its multigenerational effects on fertility and ovarian function.
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The food, beverages and products that women are exposed to before and during pregnancy can have lifelong consequences for babies in the womb. This concept is known as fetal programming. Introducing endocrine-disrupting chemicals (EDCs; toxins) during critical moments of fetal development can significantly impact the child’s health, development and fertility. These negative impacts may even compound in future generations.
“However, our understanding of the negative effects of chemicals on health in women is less than those in men [24].”
Acrylamide
Frying, roasting or baking starchy food at high temperatures produces a Maillard reaction. A problematic result of this reaction is the formation of a chemical compound called acrylamide (ACR). Acrylamide can be found in many common foods, including french fries, chips, bread, crackers, coffee, and so on. Exposure to this chemical during pregnancy has been linked to reduced development and reproductive function.
“Based on the formation of ACR in food during high temperatures and its presence in water and cosmetics [25, 26], this potential EDC may constitute a major problem for human health and could notably affect female fertility by influencing the ovary structure and function.”
While the effects of ACR in-utero have been documented, researchers Nouf Aldawood, Maroua Jalouli, Abdulkarem Alrezaki, Saber Nahdi, Abdullah Alamri, Mohamed Alanazi, Salim Manoharadas, Saleh Alwasel, and Abdel Halim Harrath from King Saud University wondered how exposure to acrylamide impacts health, development and fertility after a second generation. In a new study, the team investigated exposure to this toxin and its effects on ovarian function over the course of two generations of rats. On September 6, 2022, their research paper was published in Aging’s Volume 14, Issue 17, and entitled, “Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging.”
The Study
“In our current study, the focus was on the effect of ACR during pregnancy on the ovarian function extended over two successive generations as the ovaries are considered one of the most sensitive organs to toxic substances and exposure during the fetal stage.”
The researchers raised 20 healthy female Wistar-Albino rats and mated them. Between gestation days six and 21 (delivery), five pregnant rats were dosed daily with distilled water (the control group; no ACR), five pregnant study rats were dosed daily with 2.5 mg/kg of ACR, five pregnant study rats were dosed with 10 mg/kg of ACR, and the last five pregnant rats were dosed with 20 mg/kg of ACR. Offspring exposed to ACR, or animals of the first generation (AF1), were collected, as were the offspring of the control group (CF1). Blood samples were collected and ovaries were assessed at four weeks of age. AF1 and CF1 rats were raised until maturity and mated again. All pregnant rats were dosed depending on what/how much their mother received. The AF1 and CF1 rats gave birth to the second generation: the AF2 and CF2 offspring. Again, blood samples were collected and ovaries were assessed at four weeks of age.
Results
The researchers found that the first generation of offspring from the rats dosed with ACR (AF1) had ovaries that weighed significantly more than those in the control group (CF1). Upon histoarchitecture examination of the ovaries, this weight increase may have been caused by ovarian cysts that were identified within the AF1 rats and indicated a disruption in ovarian function. Interestingly, the results were quite different in AF2 rats. The researchers were surprised to find that prenatal ACR exposure in the second generation decreased ovarian weights and increased estradiol levels, CYP19 mRNA levels and CYP19 protein expression in all three study groups. These findings in the AF2 rats indicated early ovarian aging.
“In this study, we found that the first generation reacted differently from the second generation. Indeed, maternal exposure to ACR caused an ovarian disruption in AF1 as evidenced by severe histopathological damage, development of cysts, and high apoptosis in the stroma cells, and decreased plasmatic estradiol levels and its corresponding CYP19 gene and protein expression. However, it has induced early ovarian aging in AF2 characterized by high estradiol and progesterone levels, upregulation of CYP19, and apoptotic cell death in the stroma.”
Conclusion
“Altogether, the present study suggests that the in utero multigenerational exposure to ACR highly reduced fertility and ovarian function in females of the first generation, while it has induced early ovarian aging in females of the second generation.”
This may be the world’s first study to examine the multigenerational impact of ACR exposure on ovarian function and fertility in female rat offspring. This study provides evidence that in-utero exposure to ACR can lead to ovarian dysfunction and accelerated ovarian aging. Ovarian aging is not only a potential barrier to fertility but also a major risk factor for ovarian cancer. Women should take fetal programming into grave consideration when pregnant. Results from this study have important implications for human health and fertility.
“Moreover, this study provides some interesting evidence for the eventual implication of the epigenetic impacts of endocrine disruptors on female reproduction across generations. Future studies, using genome wide DNA methylation approaches for some specific key biomarkers of ovarian development, such as CYP19, are fundamental to determine how prenatal exposure to endocrine disruptors could drive adverse secondary phenotypic effects among the future generations in both humans and animals.”
Click here to read the full research paper published by Aging.
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.
In a trending new research paper published in Aging, researchers investigated the effects of microglial activity on post-stroke inflammation and outcomes.
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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].”
“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.
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.
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.
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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.
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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
“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 behavioral, social 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 [1–4].”
“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 [45–48].”
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 socialsupport; 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.
Agingis 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.
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 biologicalclock. 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‘sVolume 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
Click here to read the full editorial paper published by Aging.
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.
