Aging & Longevity

Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition. Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline. Mimicking an age-related increase in...

Tissue-specific regulation of gene expression is essential for multicellular organisms, and RNA-binding proteins play central roles in these molecular processes. To determine how the Caenorhabditis elegans RNA-binding protein, ADR-1, regulates tissue-specific gene expression, we profiled the RNA-binding targets of ADR-1 in neural cells and assessed the effects of ADR-1 binding on neural gene expression. We identified a cohort of neural transcripts that function in lipid metabolism and are...

A central question in the fields of genetics and evolution was the nature and origin of spontaneous mutation. Bacterial genetic experiments throughout the middle of the 20th century were key to understanding how genomes change and what cellular mechanisms act to limit such change. These mechanisms are shared among all life on the planet and have implications for human diseases and aging. The purpose of this review is to highlight genetic breakthroughs during this period using bacterial systems...

Aging disrupts physiological and behavioral homeostasis, largely driven by one-carbon metabolism, mitochondrial, and metabolic imbalance. To elucidate the roles of conserved metabolic and mitochondrial genes in age-related decline, we employed genetic manipulations in vivo using Drosophila melanogaster models, in a cell-autonomous and non-cell-autonomous manner. By using panneuronal and indirect flight muscle (IFM) specific drivers, we assessed the impact of gene knockdown (KD) or overexpression...

Growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) are stress-induced cytokines increased in age-related and metabolic disorders. The aim of the present study was to analyze the association between circulating concentrations of GDF15 and FGF21 in obesity and type 2 diabetes (T2D) in the context of aging. Serum samples from 405 participants (33 with normal weight and normoglycemia (NG), 156 with obesity and NG, 157 with obesity and impaired glucose tolerance (IGT),...

CONCLUSIONS: Significant heterogeneity exists in cognitive function among older adults with CMD, characterized by three distinct profiles. Varied transition patterns and probabilities underscore the importance of identifying and intervening with individuals at elevated risk of negative transitions, potentially improving their cognitive function.

Lactate, a byproduct of glycolysis, was first identified to induce a novel post-translational modification (PTM) known as lysine lactylation (Kla) in 2019. Kla has been shown to regulate various biological processes, including transcription, metabolism, cell proliferation, and inflammatory responses, which are pivotal in both tumorigenesis and cellular aging. Initially, Kla was identified as an epigenetic marker on histones, where it regulates gene transcription. However, more recent studies...

CONCLUSIONS: A 6-month program of progressive resistance exercise combined with nutritional support improved muscle mass and strength in postmenopausal women with osteosarcopenia. Although the HE group showed less improvement at earlier time points, their muscle strength and physical performance were comparable to those of the RE group by the end of the intervention.

The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each...

Cartilaginous fishes (e.g., sharks, rays, and skates) cannot see blue or violet light, potentially because they lack the shortwave-sensitive cone opsin gene (sws). Widespread gene loss can occur during evolution, but the evolutionary mechanisms underlying sws loss remains unclear. Here, we construct whole-genome assemblies of Okamejei kenojei (skate) and Prionace glauca (blue shark). We then analyze the distribution characteristics and intragroup differences of opsin-related genes in...

Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), a transition driven by cellular senescence, a state of irreversible cell-cycle arrest. However, the molecular mechanisms promoting this pathological process remain unclear. Here we show that the channel protein Pannexin1 (Panx1) promotes this detrimental senescence and subsequent kidney fibrosis. We found that Panx1 functions in a noncanonical role as a calcium (Ca^(2+)) leak channel within the endoplasmic reticulum (ER), a key...

We present direct sequencing methodologies, scTAPS for 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and scCAPS + specifically for 5hmC, enabling quantitative detection of 5mC and 5hmC at single-base resolution and single-cell level. Achieving approximately 90% mapping efficiency, our plate-based methods accurately recover 5mC and 5hmC profiles in CD8 + T and mouse embryonic stem cells. Notably, scCAPS + reveals a global increase in 5hmC across neuronal and non-neuronal cells in the...

The concept of cognitive reserve explains how the brain maintains function despite age-related changes or neuropathological damage. Factors such as education, cognitive stimulation, and physical activity contribute to strengthening this reserve. While research has highlighted the benefits of structured exercise, less attention has been given to the impact of incidental physical activity (IPA) everyday, unplanned movements like walking or household chores. This study examined the relationship...

CONCLUSION: Our results reveal less activation of the task-relevant areas in participants from Okinawa as compared to Dutch participants. It could be hypothesized, with caution, that Okinawan older adults may need less executive processing resources to perform the task. Other differences in activation may be related to different strategy use, which may be studied in more detail in future investigations.

Patterns of brain aging are generally conserved among primates; however, there is marked variation in the observed rate among individuals, species, and brain regions. The hippocampus is a region particularly susceptible to the aging process. To better understand how the hippocampus changes over the lifespan, we measured gene expression in 96 banked hippocampus samples from adult male and female rhesus macaques aged 3-35 years old. Importantly, our dataset included representation across adulthood...

Sodium chloride (NaCl) is an essential nutrient, but it is toxic in excess. In humans, excessive dietary NaCl can cause high blood pressure, which contributes to age-related diseases, including stroke and heart disease. We used Caenorhabditis elegans to elucidate how NaCl levels influence animal aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here, we report that the supplemental NaCl in standard NGM,...

Normal aging is associated with decline in dopamine function. Factors associated with individual differences in dopamine decline rates remain unclear but are important to map to spare dopamine-related functions, such as cognition. Here we focused on manifestations of cerebral small-vessel disease from magnetic resonance imaging (white-matter lesions, lacunes, and perivascular space dilation) and vascular risk factors (e.g., hypertension, body mass index (BMI), and hyperlipidemia). We assessed...

Sarcopenia is characterized by aging-related progressive loss of muscle mass and function; however, the specific and sensitive biomarkers are still limited. Biometals and trace elements provide a potential connection linking the environment and lifestyle to pathological processes of sarcopenia. The aim of the present study was to investigate the relationship between urinary trace elements levels and the presence of sarcopenia. A total of 100 older adults aged ≥65 years consisting of 50 patients...

CONCLUSION: ABLE demonstrated the feasibility of recruiting biologically older yet generally healthy middle-aged adults for gerotherapeutic interventions.

CONCLUSION: It was determined that nurses' views on old age and aging affect their attitudes towards the older patients. It was observed that nurses' views on old age and aging were negative, but their attitudes towards the older patients were positive.