Aging & Longevity

Despite significant research, mechanisms underlying the failure of islet beta cells that result in type 2 diabetes (T2D) are still under investigation. Here, we report that Sox9, a transcriptional regulator of pancreas development, also functions in mature beta cells. Our results show that Sox9-depleted rodent beta cells have defective insulin secretion, and aging animals develop glucose intolerance, mimicking the progressive degeneration observed in T2D. Using genome editing in human stem...

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival,...

Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited. Glycerophosphocholine phosphodiesterase 1 (Gpcpd1) is a highly abundant muscle enzyme that hydrolyzes glycerophosphocholine (GPC). The physiological functions of Gpcpd1 remain largely unknown. Here we show, in mice, that the Gpcpd1-GPC metabolic pathway is...

Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of...

Progressive neurocognitive dysfunction is the leading cause of a reduced quality of life in patients with primary brain tumors. Understanding how the human brain responds to cancer and its treatment is essential to improve the associated cognitive sequelae. In this study, we performed integrated transcriptomic and tissue analysis on postmortem normal-appearing non-tumor brain tissue from glioblastoma (GBM) patients that had received cancer treatments, region-matched brain tissue from unaffected...

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices^(1,2). A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode^(3-5). Furthermore, it acts as a barrier...

Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation bias toward myeloid lineages. However, the molecular mechanism behind HSC aging remains largely unknown. In this study, we observed that RNA N¹-methyladenosine-generating methyltransferase TRMT6-TRMT61A complex is increased in aged murine HSCs due to aging-declined CRL4^(DCAF1)-mediated ubiquitination degradation signaling. Unexpectedly, no difference of tRNA N¹-methyladenosine methylome is...

Aqueous sodium-ion batteries are practically promising for large-scale energy storage, however energy density and lifespan are limited by water decomposition. Current methods to boost water stability include, expensive fluorine-containing salts to create a solid electrolyte interface and addition of potentially-flammable co-solvents to the electrolyte to reduce water activity. However, these methods significantly increase costs and safety risks. Shifting electrolytes from near neutrality to...

Genetic variation at the transmembrane protein 106B gene (TMEM106B) has been linked to risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) through an unknown mechanism. We found that presence of the TMEM106B rs3173615 protective genotype was associated with longer survival after symptom onset in a postmortem FTLD-TDP cohort, suggesting a slower disease course. The seminal discovery that filaments derived from TMEM106B is a common feature in aging and, across a range of...

Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation of mitochondrial DNA (mtDNA) mutations. However, little is known about how accumulated mtDNA mutations modulate intestinal homeostasis. We observe the accumulation of mtDNA mutations in the small intestine of aged male mice, suggesting an association with physiological intestinal aging. Using polymerase gamma (POLG) mutator mice and wild-type mice, we generate male mice with progressive mtDNA mutation...

Aluminum alloys play an important role in circular metallurgy due to their good recyclability and 95% energy gain when made from scrap. Their low density and high strength translate linearly to lower greenhouse gas emissions in transportation, and their excellent corrosion resistance enhances product longevity. The durability of Al alloys stems from the dense barrier oxide film strongly bonded to the surface, preventing further degradation. However, despite decades of research, the individual...

Male reproductive traits such as ejaculate size and quality, are expected to decline with advancing age due to senescence. It is however unclear whether this expectation is upheld across taxa. We perform a meta-analysis on 379 studies, to quantify the effects of advancing male age on ejaculate traits across 157 species of non-human animals. Contrary to predictions, we find no consistent pattern of age-dependent changes in ejaculate traits. This result partly reflects methodological limitations,...

Exergame training, in which video games are used to promote exercise, can be tailored to address cognitive and physical risk factors for falls and is a promising method for fall prevention in older people. Here, we performed a randomized clinical trial using the smart±step gaming system to examine the effectiveness of two home-based computer game interventions, seated cognitive training and step exergame training, for fall prevention in community-dwelling older people, as compared with a...

A decline in hematopoietic stem cell (HSC) function is believed to underlie hematological shortcomings with age; however, a comprehensive molecular understanding of these changes is currently lacking. Here we provide evidence that a transcriptional signature reported in several previous studies on HSC aging is linked to stress-induced changes in gene expression rather than aging. Our findings have strong implications for the design and interpretation of HSC aging studies.

Foxp3^(+)CD4^(+) regulatory T (Treg) cells found within tissues regulate local immunity, inflammation, and homeostasis. Tregs in epididymal visceral adipose tissue (eVAT) are critical regulators of local and systemic inflammation and metabolism. During aging and under obesogenic conditions, eVAT Tregs undergo transcriptional and phenotypic changes and are important for containing inflammation and normalizing metabolic indices. We have employed single-cell RNA sequencing, single-cell Tra and Trb...

Physical activity is consistently associated with better health and longer life spans. However, the extent to which length and intensity of exercise across the life course impact health outcomes relative to current activity is undefined. Participants of the Baltimore Longitudinal Study of Aging were asked to categorize their level of physical activity in each decade of life from adolescence to the current decade. In linear mixed effects models, self-reported past levels of physical activity were...

Doxorubicin (Dox), a widely used treatment for cancer, can result in chemotherapy-induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox treatment has also been used as a model of aging. However, it is unclear if Dox induces brain changes similar to that observed during aging since Dox does not readily enter the brain. Rather, the mechanism for chemobrain likely involves the induction of peripheral cellular...

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants...

Lipid droplets are the essential organelle for storing lipids in a cell. Within the variety of the human body, different cells store, utilize and release lipids in different ways, depending on their intrinsic function. However, these differences are not well characterized and, especially in the context of ageing, represent a key factor for cardiometabolic diseases. Whole body lipid homeostasis is a central interest in the field of cardiometabolic diseases. In this review we characterize lipid...

Skin aging is a complex process influenced by intrinsic factors and environmental stressors, including ultraviolet (UV) radiation and air pollution, among others. In this study, we investigated the effects of UVA and UVB radiation, combined with urban particulate matter (UPM), on human dermal fibroblasts (HDF). We show here that treatment of HDF with a subcytotoxic dose of UVA/UVB results in a series of events leading to mitochondrial dysfunction, increased ROS levels, and DNA damage. These...