
Aging-US
Cancer and aging are two sides of age-related tumorigenesis.
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity
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Aug 13, 2024 • 3min
Lipid Accumulation Drives Cellular Senescence in Dopaminergic Neurons
BUFFALO, NY- August 13, 2024 – A new #research perspective was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 14 on July 19, 2024, entitled, “Lipid accumulation drives cellular senescence in dopaminergic neurons.”
As highlighted in the Abstract of this perspective, Parkinson’s disease (PD) is an age-related movement disorder caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the midbrain. However, the underlying causes of this DA neuron loss in PD are unknown, and there are currently no effective treatments to prevent or slow neuronal loss or the progression of related symptoms.
In their perspective, researchers Taylor Russo and Markus Riessland from Stony Brook University found that artificially inducing GluCer accumulation leads to cellular senescence of DA neurons. This suggests that lipid aggregation plays a crucial role in the pathology of PD by driving senescence in these vulnerable neurons.
“Here, we discuss the relevance of the age-related aggregation of lipids as well as the direct functional link between general lipid aggregation, cellular senescence, and inflammaging of DA neurons.”
Additionally, they propose that the expression of a cellular senescence phenotype in the most vulnerable neurons in PD can be triggered by lysosomal impairment and lipid aggregation.
“Importantly, we highlight additional data that perilipin (PLIN2) is significantly upregulated in senescent DA neurons, suggesting an overall enrichment of lipid droplets (LDs) in these cells.”
DOI - https://doi.org/10.18632/aging.206030
Corresponding author - Markus Riessland - markus.riessland@stonybrook.edu
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Keywords - aging, lipids, cellular senescence, Parkinson’s disease, glucosylceramides, lysosomes, neuroinflammation
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Aug 7, 2024 • 2min
mTORC1 in Classical Monocytes: Links to Human Size Variation & Neuropsychiatric Disease
BUFFALO, NY- August 7, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 14 on July 26, 2024, entitled, “mTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease.”
In this new study, researchers Karl Berner, Naci Oz, Alaattin Kaya, Animesh Acharjee, and Jon Berner from Woodinville Psychiatric Associates, Virginia Commonwealth University, University of Birmingham, University Hospitals Birmingham, and MRC Health Data Research UK, aimed to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response.
Their results showed that mTORC1 activity correlated highly with classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism).
“Our data suggest that human variability of mTORC1 gain of function observed during the differentiation of stem-like monocytes into vascular tissue-resident macrophages correlates with physical size, subsets of neuropsychiatric disease, and clinical ketamine or rapamycin response.”
DOI - https://doi.org/10.18632/aging.206033
Corresponding author - Jon Berner - jonbernermd@gmail.com
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Keywords - aging, ketamine, lithium, monocyte, mTORC1, rapamycin
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Aug 6, 2024 • 2min
Targeted Cancer Therapy: Initial High Concentration May Slow Down Selection for Resistance
BUFFALO, NY- August 6, 2024 – On July 28, 2024, Mikhail V. Blagosklonny M.D., Ph.D., from Roswell Park Comprehensive Cancer Center #published a new #editorial in Volume 16, Issue 14 of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), entitled, “Targeted cancer therapy: the initial high concentration may slow down the selection for resistance.”
“Unfortunately, any targeted therapy is, always, started with low levels of the drug in the organism, selecting for drug resistance. One should propose that initial drug levels must be maximized, and durations may be minimized, ideally, as portions of preemptive combination of targeted drugs.”
Read the full paper: DOI: https://doi.org/10.18632/aging.206046
Corresponding Author: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com
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Keywords - aging, lung cancer, resistance, brain metastases, METex14, capmatinib, rapamycin
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Aug 5, 2024 • 3min
Association Between Osteoporosis and Telomere Shortening
BUFFALO, NY- August 5, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 14, entitled, “Association between osteoporosis and the rate of telomere shortening.”
A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial.
In this current study, researchers Myung-Hoon Han , Hyuk Sung Kwon, Mina Hwang, Hyun-Hee Park, Jee Hyang Jeong, Kyung Won Park, Eun-Joo Kim, Soo Jin Yoon, Bora Yoon, Jae-Won Jang, Jin Yong Hong, Seong Hye Choi, and Seong-Ho Koh from Hanyang University Guri Hospital, Hanyang University Graduate School of Biomedical Science and Engineering, Ewha Womans University College of Medicine, Dong-A University College of Medicine, Pusan National University Hospital, Eulji University Hospital, Eulji University School of Medicine, Konyang University College of Medicine, Kangwon National University School of Medicine, Yonsei University Wonju College of Medicine, and Inha University College of Medicine, aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort.
“We compared the LTL values for each participant at baseline and over a 2-year follow-up period.”
Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study.
Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038).
“We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort.”
DOI - https://doi.org/10.18632/aging.206034
Corresponding authors - Seong Hye Choi - seonghye@inha.ac.kr, and Seong-Ho Koh - ksh213@hanyang.ac.kr
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Keywords - aging, leukocyte telomere length, osteoporosis, interleukin-6, prospective cohort
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 23, 2024 • 3min
Co-analysis of Methylation Platforms for Signatures of Biological Aging in the Domestic Dog
BUFFALO, NY- July 23, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 13, entitled, “Co-analysis of methylation platforms for signatures of biological aging in the domestic dog reveals previously unexplored confounding factors.”
Chronological age reveals the number of years an individual has lived since birth. By contrast, biological age varies between individuals of the same chronological age at a rate reflective of physiological decline. Differing rates of physiological decline are related to longevity and result from genetics, environment, behavior, and disease. The creation of methylation biological age predictors is a long-standing challenge in aging research due to the lack of individual pre-mortem longevity data.
In this new study, researchers Aitor Serres Armero, Reuben M. Buckley, Lajoyce Mboning, Gabriella J. Spatola, Steve Horvath, Matteo Pellegrini, and Elaine A. Ostrander from the National Human Genome Research Institute, the University of California Los Angeles, and Altos Labs ask whether dogs experience changes in their epigenetic age at a rate predicted by breed longevity.
“The consistent differences in longevity between domestic dog breeds enable the construction of biological age estimators which can, in turn, be contrasted with methylation measurements to elucidate mechanisms of biological aging.”
The researchers drew on three flagship methylation studies using distinct measurement platforms and tissues to assess the feasibility of creating biological age methylation clocks in the dog. They expanded epigenetic clock building strategies to accommodate phylogenetic relationships between individuals, thus controlling for the use of breed standard metrics. The team observed that biological age methylation clocks are affected by population stratification and require heavy parameterization to achieve effective predictions.
“Finally, we observe that methylation-related markers reflecting biological age signals are rare and do not colocalize between datasets.”
DOI - https://doi.org/10.18632/aging.206012
Corresponding author - Elaine A. Ostrander - eostrand@mail.nih.gov
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Keywords - aging, biological age, methylation, dog, lifespan, penalized regression
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 18, 2024 • 5min
Links Between Exercise, Senescence, and Lung Health
Over the human lifespan, our cells encounter numerous stressors that can trigger an intrinsic defense mechanism called cellular senescence. Cellular senescence is characterized by irreversible growth arrest and can act as a safeguard against cancer. However, when senescent cells accumulate in various tissues as we age, it can contribute to tissue degeneration and chronic diseases.
The senescence-associated secretory phenotype (SASP), a hallmark of senescent cells, plays a critical role by secreting inflammatory factors, proteases, and growth factors, disrupting tissue balance and fueling pathological conditions. Consequently, selectively eliminating senescent cells has emerged as a promising therapeutic strategy, potentially restoring tissue function and mitigating age-related disorders.
Full blog - https://aging-us.org/2024/07/links-between-exercise-senescence-and-lung-health/
Research Paper DOI - https://doi.org/10.18632/aging.205976
Corresponding author - Masataka Sugimoto - msugimot@tmig.or.jp
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Keywords - aging, senescence, exercise, PEDF, myokine, COPD
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 17, 2024 • 4min
Modulating Lung Fibroblast Activation via Senolysis of Senescent Human Alveolar Epithelial Cells
BUFFALO, NY- July 17, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 13, entitled, “Modulating in vitro lung fibroblast activation via senolysis of senescent human alveolar epithelial cells.”
Idiopathic pulmonary fibrosis (IPF) is an age-related disease with poor prognosis and limited therapeutic options. Activation of lung fibroblasts and differentiation to myofibroblasts are the principal effectors of disease pathology, but damage and senescence of alveolar epithelial cells, specifically type II (ATII) cells, has recently been identified as a potential trigger event for the progressive disease cycle. Targeting ATII senescence and the senescence-associated secretory phenotype (SASP) is an attractive therapeutic strategy; however, translatable primary human cell models that enable mechanistic studies and drug development are lacking.
In this new study, researchers Joseph S. Spina, Tracy L. Carr, Lucy A. Phillips, Heather L. Knight, Nancy E. Crosbie, Sarah M. Lloyd, Manisha A. Jhala, Tony J. Lam, Jozsef Karman, Meghan E. Clements, Tovah A. Day, Justin D. Crane, and William J. Housley from AbbVie Bioresearch Center and Northeastern University describe a novel system of conditioned medium (CM) transfer from bleomycin-induced senescent primary alveolar epithelial cells (AEC) onto normal human lung fibroblasts (NHLF) that demonstrates an enhanced fibrotic transcriptional and secretory phenotype compared to non-senescent AEC CM treatment or direct bleomycin damage of the NHLFs.
“In the current study, we confirm the presence of senescent cell populations within the human IPF lung, as well as assess primary cell reagents for sensitivity to senescent cell targeting therapies.”
In this system, the bleomycin-treated AECs exhibited classical hallmarks of cellular senescence, including SASP and a gene expression profile that resembles aberrant epithelial cells of the IPF lung. Fibroblast activation by CM transfer was attenuated by pre-treatment of senescent AECs with the senolytic Navitoclax and AD80, but not with the standard of care agent Nintedanib or senomorphic JAK-targeting drugs (e.g., ABT-317, ruxolitinib). This model provided a relevant human system for profiling novel senescence-targeting therapeutics for IPF drug development.
“Taken together, the model described herein provides a physiologically relevant, primary human cell system to study the effects of alveolar epithelial cell senescence on lung fibroblasts in the context of chronic fibrotic lung disease.”
DOI - https://doi.org/10.18632/aging.205994
Corresponding author - Tovah A. Day - t.day@northeastern.edu
Video short - https://www.youtube.com/watch?v=rpmo2PlGDKc
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About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 15, 2024 • 4min
Roles of PEDF in Exercise-induced Suppression of Senescence and its Impact on Lung Pathology in Mice
BUFFALO, NY- July 15, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 13, entitled, “Roles of pigment epithelium-derived factor in exercise-induced suppression of senescence and its impact on lung pathology in mice.”
Senescent cells contribute to tissue aging and underlie the pathology of chronic diseases. The benefits of eliminating senescent cells have been demonstrated in several disease models, and the efficacy of senolytic drugs is currently being tested in humans. Exercise training has been shown to reduce cellular senescence in several tissues; however, the mechanisms responsible remain unclear.
In this new study, researchers Hiromichi Tsushima, Hirobumi Tada, Azusa Asai, Mikako Hirose, Tohru Hosoyama, Atsushi Watanabe, Taro Murakami, and Masataka Sugimoto from Tokyo Metropolitan Institute for Geriatrics and Gerontology, Shigakkan University, and National Center for Geriatrics and Gerontology investigated myocyte-secreted factors with the potential to suppress cellular senescence, aiming to explore their protective effects against lung disease.
“We found that myocyte-derived factors significantly extended the replicative lifespan of fibroblasts, suggesting that myokines mediate the anti-senescence effects of exercise.”
A number of proteins within myocyte-derived factors were identified by mass spectrometry. Among these, pigment epithelium-derived factor (PEDF) exerted inhibitory effects on cellular senescence. Eight weeks of voluntary running increased PEDF levels in skeletal muscles and suppressed senescence markers in the lungs. The administration of PEDF reduced senescence markers in multiple tissues and attenuated the decline in respiratory function in the pulmonary emphysema mouse model. The researchers also showed that blood levels of PEDF inversely correlated with the severity of COPD in patients.
“Collectively, these results strongly suggest that PEDF contributes to the beneficial effects of exercise, potentially suppressing cellular senescence and its associated pathologies.”
DOI - https://doi.org/10.18632/aging.205976
Corresponding authors - Masataka Sugimoto - msugimot@tmig.or.jp
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Keywords - aging, senescence, exercise, PEDF, myokine, COPD
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 10, 2024 • 4min
Aging Exacerbates Oxidative Stress and Liver Fibrosis in an Animal Model of Down Syndrome
BUFFALO, NY- July 10, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 12, entitled, “Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome.”
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals.
In this new study, researchers Sebastiano Giallongo, Jessica Ferrigno, Rosario Caltabiano, Giuseppe Broggi, Amer M. Alanazi, Alfio Distefano, Emanuela Tropea, Antonella Tramutola, Marzia Perluigi, Giovanni Li Volti, Eugenio Barone, and Ignazio Alberto Barbagallo from the University of Catania, King Saud University, and Sapienza University of Rome investigated the impact of aging on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice).
“Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation.”
DS liver exhibited an altered inflammatory response and mitochondrial fitness as the researchers showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displayed dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver revealed increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, their findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients.
“These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.”
DOI - https://doi.org/10.18632/aging.205970
Corresponding author - Giovanni Li Volti - livolti@unict.it
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Keywords - aging, Down Syndrome, oxidative stress, liver
About Aging-US
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Jul 9, 2024 • 3min
Aging Retinal Pigmented Epithelium: Omics-based Insights Into Vision Decline
BUFFALO, NY- July 9, 2024 – A new #editorial paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 12, entitled, “Aging retinal pigmented epithelium: omics-based insights into vision decline.”
In this new editorial, researchers Ioan V. Matei and Luminita Paraoan from Edge Hill University discuss vision decline with aging. Of all senses affected by aging, vision decline arguably has the most impactful relationship with overall wellbeing, health and personal autonomy. However, while the ensuing importance of vision loss has long been recognised from a public health perspective given an increasingly aging population, understanding the molecular and cellular mechanisms driving age-related pathological changes is still in its infancy.
“This matter is, therefore, critical for tackling sensory impairment and ensuring healthy aging.”
The retinal pigmented epithelium (RPE), the cellular monolayer located between the neuroretina and the highly vascularized choroid, from which it is separated by Bruch’s membrane (BrM), has a critical role in human vision and performs essential functions throughout life for maintaining the retinal homeostasis. RPE is a specialised, fully differentiated tissue that is mitotically inactive, with no regenerative potential. Unsurprisingly, given all its characteristics, functions and metabolic demands, the RPE is particularly susceptible to aging, sustaining significant morphologic and physiologic changes.
“Aging is recognised as the highest risk factor for age-related macular degeneration (AMD), the leading cause of adult visual impairment and blindness in the Northern Hemisphere, which is directly linked to specific pathological changes of the RPE located in the macula, i.e., the central part of retina; these changes, therefore, affect central vision required for reading, driving, and discerning details of pictures, faces, shapes and colors.”
DOI - https://doi.org/10.18632/aging.205914
Corresponding author - Luminita Paraoan - Luminita.Paraoan@edgehill.ac.uk
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Keywords - aging, RPE, vision, omics
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