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BMI Correlates With Accelerated Epigenetic Aging in Young Adults

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In a recent study, researchers from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between measures of obesity and DNA methylation in young adults.

BMI Correlates With Accelerated Epigenetic Aging in Young Adults

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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While the study of genetics focuses on heredity and alterations in the genetic code itself, epigenetics refers to the changes in gene expression that occur as a result of environmental or lifestyle factors. Advances in epigenetic research have allowed measures of DNA methylation (DNAm) (epigenetic clocks) to illustrate clear links between obesity, accelerated epigenetic aging and a variety of negative health outcomes in older adults. Despite these advances, there is a lack of research about these correlations and sex-based variations among young adults. The ability to detect accelerated epigenetic aging in young adulthood could potentially be used to prevent the onset of chronic diseases and improve health outcomes later in life.

“Moreover, few studies have included replication across measures of obesity and epigenetic aging to examine the robustness or specificity of these effects. Finally, little is known about sex differences in the links between obesity and epigenetic aging, despite evidence of substantial sex dimorphism in both physiological and epigenetic aging [20].”

In a recent study, researchers Christy Anne Foster, Malcolm Barker-Kamps, Marlon Goering, Amit Patki, Hemant K. Tiwari, and Sylvie Mrug from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between obesity and measures of DNAm in young adults. They also investigated whether there is a sex-dependant correlation between obesity and DNAm in young adults. On January 18, 2023, their research paper was published in Aging’s Volume 15, Issue 2, and entitled, “Epigenetic age acceleration correlates with BMI in young adults.”

Research and Results

Here, the researchers explored the relationship between measures of obesity and epigenetic age acceleration in young adults. The team included a cross-sectional community sample of 290 healthy young adults—with 60% being female, 80% African American, 18% White, and a total mean age of 27 years old. The researchers measured participant BMI and waist circumference, and also calculated their epigenetic age acceleration using four epigenetic age estimators (derived from salivary DNA): Hannum DNAm, Horvath DNAm, Phenoage DNAm, and GrimAge DNAm. In addition, they collected data on covariates, including age, sex, race, parental education, and income-to-needs ratio.

After covariates were adjusted for, the researchers found that DNAm PhenoAge was higher in participants who had higher body mass index (BMI) and waist circumference in both sexes, with a stronger effect on BMI in males compared to females. Horvath DNA methylation age was associated with participants who had larger waist circumferences, but not BMI. Higher Hannum DNAm age was associated with both higher BMI and waist circumference in men, but not in women. In this study, GrimAge was not associated with either BMI or waist circumference. As a whole, none of the associations with the DNAm indicators varied by race. The researchers found that scoring higher on one or more of the four DNAm indicators was associated with an older chronological age, lower socioeconomic status, being female and White, as well as saliva cell composition. 

“Together, these results suggest that higher BMI and waist circumference are associated with higher epigenetic age in young adulthood. Because the analyses adjusted for chronological age, associations with higher epigenetic age indicate faster epigenetic aging [22]. Importantly, this study demonstrated associations between obesity and epigenetic aging using DNA from saliva, which involves a non-invasive sample collection compared to other tissues (e.g., blood) and thus can be more readily translated into clinical practice, highlighting the usefulness in young adults.”

Significance and Limitations

These findings are significant because they suggest that body weight plays a role in determining epigenetic age acceleration, which in turn can affect overall health and lifespan. Previous research has shown that epigenetic age acceleration is associated with increased risk for age-related diseases such as cardiovascular disease, type 2 diabetes and certain cancers. However, it is important to note that this study only shows a correlation between BMI and epigenetic age acceleration and does not provide evidence of causality. It is possible that other factors, such as diet, exercise and stress levels, could also contribute to the relationship between BMI and epigenetic age acceleration.

The authors were forthcoming about several study limitations in their research paper, including a relatively small sample size which limited statistical power and precluded rigorous analysis of individual CpG sites. The original sample was locally representative but experienced some differential attrition over time, which could limit generalizability to certain populations. Epigenetic clocks have been tested primarily in White populations and may be less relevant to African American individuals who comprised the majority of this sample. This study used salivary DNA, so replication using DNA extracted from other tissues will be important for future work. The cross-sectional design did not allow testing directional effects between BMI and epigenetic aging over time. None of the CpGs used in calculating methylation age were part of known causal effect on BMI as per Mendelian Randomization studies; further modeling with outcomes from other tissues impacted by obesity may provide more insight into methylation aging process.

Conclusions

In conclusion, this study sheds light on the relationship between BMI and epigenetic age acceleration in young adults. The results suggest that young adults with higher BMIs may be aging faster and at a higher risk for age-related diseases. These findings highlight the importance of maintaining a healthy weight and lifestyle, not only for weight management but also for overall health and lifespan.

In the context of the growing obesity epidemic and the increasing focus on personalized medicine and preventive health, this study provides valuable insights into the potential health impacts of body weight and the role of epigenetics in health and disease. Further research is needed to fully understand the mechanisms behind this relationship and to determine the best approaches for improving health and lifespan in young adults.

“In conclusion, this study extends prior research by demonstrating the association between obesity and salivary epigenetic aging in young adult males and females. These findings are of interest to those who are interested in epigenetic age acceleration as a potential biomarker. They also support future research examining obesity as a causal risk factor for epigenetic age acceleration. The findings underscore the importance of testing sex differences and including multiple epigenetic clocks in future research. Overall, the present results add to mounting evidence that obesity affects cellular aging across multiple tissues early in the lifespan.”

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

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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.

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

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Gene Linked to Osteoporosis Risk in Postmenopausal Asian Women

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In this recent study, researchers compared three IGF-1 polymorphisms in postmenopausal Asian women and investigated their potential link to osteoporosis.

Gene Linked to Osteoporosis Risk in Postmenopausal Asian Women

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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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.

In a recent study, researchers Sui-Lung Su, Yung-Hsun Huang, Yu-Hsuan Chen, Pi-Shao Ko, Wen Su, Chih-Chien Wang, and Meng-Chang Lee from the Tri-Service General Hospital and National Defense Medical Center in Taipei, Taiwan, explored the relationship between IGF-1 polymorphisms rs35767, rs2288377 and rs5742612 and the development of osteoporosis in postmenopausal Asian women. Their new research paper was published in Aging’s Volume 15, Issue 1, entitled, “A case-control study coupling with meta-analysis elaborates decisive association between IGF-1 rs35767 and osteoporosis in Asian postmenopausal females.”

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

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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.

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

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How Hidden Markov Models Could Elucidate Multimorbidity in Aging

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In a new study, researchers investigated longitudinal multimorbidity patterns among older adults from a Swedish urban population.

Figure 1. Evolution and transitions of multimorbidity patterns over time by age group (N=3,363).
Figure 1. Evolution and transitions of multimorbidity patterns over time by age group (N=3,363).
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Multimorbidity is a term that refers to living with two or more chronic diseases at the same time, and the prevalence of this phenomenon increases with age. In addition, humans tend to evolve and transition into distinct patterns of multimorbidity. These still ill-defined patterns of multimorbidity may offer a window of opportunity for researchers. Since the aging population continues to grow in many parts of the world, researchers are motivated to better understand these patterns and how they evolve and transition over time in order to develop interventions and therapeutics for healthier aging. However, this is a challenging task for several reasons.

“Multimorbidity is associated with a higher risk of polypharmacy and decreased quality of life, and challenges the decision-making of clinicians that lack effective guidelines for the management and treatment of patients with cohexisting complex diseases [4].”

Multimorbidity Patterns

While researchers have investigated multimorbidity, not all studies are created equal—rendering meta-analyses largely incongruent (thus far). One reason the evolution of multimorbidity patterns is so challenging to study is because most study designs are not powered to account for the dynamic nature of multimorbidity in old age. Another reason is that various studies use different lists of diseases. (Some studies include ten conditions or less and others include 200+ conditions.) Finally, most statistical methods used to organize data are not able to properly handle the complexity of multimorbidity.

“Exploring how multimorbidity patterns evolve throughout people’s lives and the time subjects remain within specific patterns is still an under-researched area [7, 8]. The understanding of how diseases cluster longitudinally in specific age groups would pave the way to the design of new prognostic tools, as well as new preventive and, eventually, therapeutic approaches.”

In a new study, researchers Albert Roso-Llorach, Davide L. Vetrano, Caterina Trevisan, Sergio Fernández, Marina Guisado-Clavero, Lucía A. Carrasco-Ribelles, Laura Fratiglioni, Concepción Violán, and Amaia Calderón-Larrañaga from the Jordi Gol i Gurina University Institute Foundation for Research in Primary Health Care (IDIAPJGol), Universitat Autònoma de Barcelona, Karolinska Institutet, Stockholm University, Stockholm Gerontology Research Center, University of Ferrara, Madrid Health Service, and Universitat Politecnica de Catalunya investigated the evolution of multimorbidity patterns in a longitudinal study using complex statistical models. The team published their research paper in Aging’s Volume 14, Issue 24, entitled, “12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models.”

Hidden Markov Models 

“Recently, several advanced machine-learning techniques such as non-hierarchical and hierarchical clustering techniques have been used to explore multimorbidity patterns.”

Hidden Markov Models (HMM) were developed based on the Bayesian Information Criterion. The Bayesian Information Criterion is an algorithm of inference that is used to select the best model from a set of possible models. It is a powerful technique for analyzing temporal data that can capture dynamic changes in longitudinal patterns over time. Since HMMs can account for complex longitudinal data, they are well-suited to investigate the dynamics of multimorbidity over time.

The Study

In this study, HMMs were used to investigate 3,363 older adults from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) and the evolution of their multimorbidity patterns over the course of 12 years. The aim of this research was to explore the evolution of these patterns across decades of life in older adults and to examine how they transition across different chronic diseases when further chronic diseases arise. In this cohort of study participants, the average age was 76.1 years old, 66.6% were female and 87.2% had multimorbidity at baseline.

The researchers divided the participants into three groups based on age: sexagenarians (between 60 and 66 years), septuagenarians (between 72 and 78 years) and octogenarians (81 years and over). Data used in the HMMs included age, gender, education level, self-reported chronic diseases and medications, results from a Mini Mental State Examination (MMSE), and walking speed. Data were collected from participants at baseline and at six and 12 years (three separate time points).

“At each follow-up wave, SNAC-K participants undergo an approximately five-hour-long comprehensive clinical and functional assessment carried out by trained physicians, nurses, and neuropsychologists.”

Results

The team identified four longitudinal multimorbidity patterns in each decade. The Unspecific pattern consists of participants with no specific pattern of multimorbidity. In all decades, participants showed the shortest permanence time in the Unspecific pattern. The researchers also included categories for participants who dropped out of the study or passed away.

Next, the top 10 diseases were selected out of each age group at each follow-up wave to identify the most common multimorbidity patterns. Among the sexagenarians, the multimorbidity patterns were clustered into cardiovascular and anemia, cardio-metabolic, and psychiatric-endocrine and sensorial. Among the septuagenarians, the multimorbidity patterns were clustered into cardiovascular and diabetes, neuro-vascular and skin-sensorial, and neuro-psychiatric and sensorial. Among the octogenarians, the multimorbidity patterns were clustered into respiratory-circulatory and skin, cardio-respiratory and neurological, and neuro-sensorial. The data showed that participants commonly shifted from one pattern to another. (See Figure 1.)

“In this study we identified and characterized longitudinal multimorbidity patterns among older adults from a Swedish urban population, and estimated the time they spent in each pattern as well as the probability of transitioning across different patterns throughout a 12-year follow-up period.”

Conclusions

“Our statistical approach enabled us to model the evolution and transitions of multimorbidity over time, and the results of this could be applied in the interests of healthier aging. Moreover, the age-stratified analyses allowed us to identify which disease combinations and transitions were more prevalent in each decade.”

The findings of this study suggest that multimorbidity patterns change with age and highlight the importance of understanding the dynamic nature of multimorbidity over time. Through the use of HMMs, this research was able to detect changes in the prevalence and transition of multimorbidity patterns across different decades of life. These findings can help healthcare providers and researchers better understand the complex nature of multimorbidity and develop more effective interventions for older adults. Furthermore, this research provides evidence that the use of HMMs to study longitudinal data is a useful tool for further research into multimorbidity. Additional studies with more data is needed to gain a better understanding of the interplay between multimorbidity and aging.

“Our study provides evidence that multimorbidity is dynamic and heterogeneous in old age. With increasing age, older adults experience decreasing clinical stability and progressively shorter permanence time within one same multimorbidity pattern. Moreover, a significant proportion ranging between 5.9%-22.6% belongs to an Unspecific pattern with a low burden of diseases and a promising preventive potential. Adding new variables related to drug use, environmental and genetic factors, and/or frailty to the longitudinal analysis of multimorbidity patterns may allow optimizing the epidemiological understanding and applicability of these models for patient-tailored prevention and management strategies.”

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

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

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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.

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

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Late-in-Life Interventions to Improve Cardiac Health

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In a new research perspective, researchers discuss spermidine, rapamycin, caloric restriction, and exercise training to improve cardiac health in aging individuals.

Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
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Cardiac dysfunction is a major public health concern. While it can occur for various reasons at any age, the prevalence of cardiac dysfunction dramatically increases with advancing age. Unfortunately, the underlying mechanisms of age-related cardiac decline are still largely unknown. Thus, it is essential for researchers to uncover novel strategies to improve cardiac health at advanced ages.

Autophagic Flux

An important physiological process involved in maintaining cardiovascular homeostasis is autophagic flux. Autophagic flux is the process by which cells break down and recycle their own cellular components after they have become damaged or unnecessary. This process is essential for maintaining healthy cardiac function, as it slows age-related oxidative damage, reduces the accumulation of toxic lipid and protein aggregates, and improves energy metabolism. However, the efficiency of autophagic flux decreases with age, resulting in declined cardiac function.

Given its crucial role and fading functioning, the search for strategies to improve autophagic flux may be essential for improving cardiovascular health as humans age. Researchers Jae Min Cho, Rajeshwary Ghosh, Sohom Mookherjee, Sihem Boudina, and J. David Symons from the University of Utah authored a new research perspective about nutraceutical, lifestyle and pharmacological interventions that can reduce age-associated cardiac dysfunction. On December 1, 2022, their research perspective was published in Aging’s Volume 14, Issue 23, entitled, “Reduce, Reuse, Recycle, Run ! : 4 Rs to improve cardiac health in advanced age.”

“In the following sections we review evidence that age-associated cardiac dysfunction can be Reduced by boosting cardiomyocyte autophagy (i.e., the ability to Reuse and Recycle damaged/dysfunctional proteins) via spermidine, rapamycin, and caloric-restriction. In addition, we highlight a new report indicating that a physiological intervention i.e., Running, rejuvenates cardiomyocyte autophagic flux to an extent that lessens age-associated cardiac dysfunction.”

Late-in-Life Interventions

Late-in-life interventions to improve cardiac health are particularly important since many of the world’s elderly populations are reaching advanced age with limited resources. This means that proven, inexpensive and accessible interventions to reduce cardiac dysfunction may have a profound impact on these populations. In this research perspective, the authors discuss four key interventions that reduce age-associated cardiac dysfunction: spermidine, rapamycin, caloric restriction, and exercise training. These interventions can reduce age-associated cardiac dysfunction by improving cardiac autophagy.

In October 2021, Cho et al. published a novel research paper about their study on late-in-life treadmill training in mice and its impact on autophagy, protein aggregates and heart function. The results of this study provided the first evidence that late-in-life exercise training can rejuvenate autophagic flux, clear protein aggregates and attenuate aging-associated cardiac dysfunction. In another murine study, researchers demonstrated that calorie restriction activates AMPK and increases the expression of autophagy-associated genes in the heart muscles.

Spermidine is a polyamine found in certain foods, such as legumes and nuts. A 2016 study linked spermidine to reduced age-associated cardiac dysfunction by attenuating cardiac hypertrophy and preserving diastolic function. Rapamycin is an mTOR inhibitor, immunosuppressant and anti-cancer drug. In a 2013 study, Flynn et al. were the first to report the cardiovascular effects of rapamycin in the context of aging. Rapamycin’s cardiovascular benefits include repressed pro-inflammatory signaling in heart muscles, reduced hypertrophy and preserved systolic function.

Conclusion

As the world’s population continues to age, it is increasingly important to identify interventions that can reduce age-associated cardiac dysfunction while avoiding high costs and potential side effects. In this research perspective, the researchers discussed evidence that spermidine, rapamycin, calorie restriction, and exercise training can improve autophagic flux and reduce age-associated cardiac dysfunction. While the mechanisms responsible for these improvements have yet to be fully elucidated, these strategies are cost-effective, accessible and relatively safe for elderly populations, and could provide a valuable way to improve cardiac health in advanced age.

“Findings from Cho et al. suggest that age-associated cardiac dysfunction can be re-established by Reducing (physical inactivity), Reusing (lysosomal degradation products e.g., amino acids for ATP synthesis), Recycling (damaged intracellular organelles via the lysosome and other protein degradation pathways), and Running (or increasing physical activity via any mode that can be enjoyed regularly and safely by the individual) (Figure 1).”

Click here to read the full research perspective 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.

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

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New Insights Into the Mechanisms of Sarcopenia

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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.

New Insights Into the Mechanisms of Sarcopenia

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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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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.

In a new study, researchers Matthew Triolo, Debasmita Bhattacharya and David A. Hood from York University in Toronto, Canada, aimed to characterize the time-dependent changes in denervated skeletal muscle from middle-aged mice. The team focussed on how mitochondrial turnover is impacted. On November 4, 2022, their research paper was published in Aging’s Volume 14, Issue 22, entitled, “Denervation induces mitochondrial decline and exacerbates lysosome dysfunction in middle-aged mice.”

The Study

“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.

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

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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.

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

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Is Estrogen Dysregulation Behind Alzheimer’s Pathology?

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In a new study, researchers explored Alzheimer’s disease and its potential relationship with the estrogen receptor-α gene (ESR1).

In a new study, researchers explored Alzheimer's disease and its potential relationship with the estrogen receptor-α gene (ESR1).

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 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. 

In a new study, researchers Junying Liu, Shouli Yuan, Xinhui Niu, Robbie Kelleher, and Helen Sheridan from Trinity College Dublin, Peking University and Jilin University examined the potential relationship between the estrogen receptor-α gene (ESR1) and neuroinflammation. Their research paper was published on November 1, 2022, in Aging’s Volume 14, Issue 21, and entitled, “ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process.”

“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.

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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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Aging’s Scientific Integrity Process

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The open-access journal Aging recently launched a new webpage showcasing the full Aging Scientific Integrity Process.

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BUFFALO, NY-November 8, 2022 – Scientific integrity is a crucial component of scholarly publishing for any credible journal. Peer-reviewed, open-access journal Aging (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) has recently presented its Scientific Integrity process.

Launched in 2009, Aging is an open-access biomedical journal dedicated to publishing high-quality, aging-focused research. Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. 

Aging has a scientific integrity process to ensure that publications meet a number of scrupulous criteria for authenticity and integrity. Each published paper is thoroughly analyzed by diligent reviewers and services, including multiple in-house developed image forensics softwares. A growing industry of digital technologies, tools and ideas are constantly being added to Aging’s scientific integrity toolbox. 

Aging’s Scientific Integrity process is built upon six critical components:

  1. Easily Accessible Ethics Statements
  2. Devotion to Industry Standards for Scientific Publishing
  3. Rigorous and Insightful Peer Review
  4. Detection and Zero-Tolerance of Plagiarism
  5. Leading-Edge Image Forensics
  6. Post-Publication Investigations (if needed)

You can read about each of these components in greater detail on Aging’s new Scientific Integrity webpage. 

The new webpage also depicts publishing statistics in a detailed graph (below)—showcasing a visual representation of the number of post-publication corrections and retractions by Aging compared to the industry average, between 2010 and 2022. As of September 2022, Aging’s average rate of corrections/retractions since 2009 is a low 2.33%. The industry average correction/retraction rate is 3.80%. 

Image forensics corrections/retractions (published & pending) as a percent of IF-eligible articles in Aging, 2009-2022

Aging’s highly-effective scientific integrity process allows researchers to read, share and cite Aging papers with confidence.

Click here for Aging’s full Scientific Integrity Process.

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Investigating Susceptibility to Radiation-Induced Pulmonary Fibrosis

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Researchers evaluated three different mouse strains with varying sensitivity to radiation lung fibrosis in an effort to uncover the underlying mechanisms.

Investigating Susceptibility to Radiation-Induced Pulmonary Fibrosis

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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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.”

Previous studies in mouse models have shown that there are natural variations in susceptibility to RIPF among different strains of mice. The mechanism(s) underlying this difference in susceptibility is still unknown. In a new study, researchers Eun Joo Chung, Seokjoo Kwon, Uma Shankavaram, Ayla O. White, Shaoli Das, and Deborah E. Citrin from the National Institutes of Health’s National Cancer Institute investigated differences in macrophage function across mouse strains and their potential contribution to varied RIPF susceptibility. On September 28, 2022, their research paper was published in Aging’s Volume 14, Issue 19, entitled, “Natural variation in macrophage polarization and function impact pneumocyte senescence and susceptibility to fibrosis.”

The Study

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

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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.

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

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Does A Link Exist Between Longevity, Aging and Heart Rate Parameters?

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Researchers investigated the relationship between familial longevity, chronological age and heart rate parameters, including heart rate variability and 24-h rhythms.

ecg ekg screen, heart rate
Closeup view of an ECG/EKG display

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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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.”

The Study

In a new study, researchers Janneke M. Wiersema, Annelies E.P. Kamphuis, Jos H.T. Rohling, Laura Kervezee, Abimbola A. Akintola, Steffy W. Jansen, P. Eline Slagboom, Diana van Heemst, and Evie van der Spoel from Leiden University Medical Center and Catharina Hospital used continuous ambulatory ECG measurements collected over a period of 24 to 90 hours to investigate the relationship between heart rate parameters and familial longevity and chronological age. On August 16, 2022, their research paper was published in Aging’s Volume 14, Issue 18, and entitled, “The association between continuous ambulatory heart rate, heart rate variability, and 24-h rhythms of heart rate with familial longevity and aging.”

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

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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.

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

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Adenoviral COVID-19 Vaccine Elicits Robust Immunity in Elderly Cohort

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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
Adenoviral COVID-19 Vaccine Elicits Robust Immunity in Elderly Cohort

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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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.

The Study

In a new study, researchers Rodrigo Hernán Tomas-Grau, Carolina Maldonado-Galdeano, Mónica Aguilar López, Esteban Vera Pingitore, Patricia Aznar, María Elena Alcorta, Eva María del Mar Vélez, Agustín Stagnetto, Silvana Estefanía Soliz-Santander, César Luís Ávila, Sergio Benjamín Socias, Dardo Costas, Rossana Elena Chahla, Gabriela Perdigón, Rosana Nieves Chehín, Diego Ploper, and Silvia Inés Cazorla from Instituto de Investigación en Medicina Molecular y Celular Aplicada, Centro de Referencia para Lactobacilos, Public Healthcare Administration (SIPROSA), and Néstor Kirchner Hospital investigated whether Gam-COVID-Vac could induce a robust humoral immunoresponse in elderly patients. On September 21, 2022, their research paper was published in Aging’s Volume 14, Issue 18, entitled, “Humoral immunoresponse elicited against an adenoviral-based SARS-CoV-2 coronavirus vaccine in elderly patients.”

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

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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.

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

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