Aging & Longevity

Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their...

Hematopoietic stem cells (HSCs) are multipotent self-renewing cells that give rise to all types of blood cells. Past research has identified that long-term hematopoietic stem cells in young mice and humans produce a balanced output of lymphoid and myeloid cells, while in old age, they are largely replaced by myeloid-biased HSCs (My-HSC). It has not yet been determined whether this transition results from epigenetic changes in a single population of HSC or if two or more subsets of HSCs exist...

Low concentrations of chemicals are widespread in the environment, but exploration of the effects of their chronic exposures on animal life span in the wild is limited. Field investigations showed that fish populations of lake skygazer (Culter dabryi) with chronic low-dose chlorpyrifos loads had shortened telomeres and truncated age structures. Laboratory experiments confirmed that chronic low-dose chlorpyrifos exposure induced telomere degradation and reduced survival in a dose- and...

Harms of chlorpyrifos emerge in polluted lakes and laboratory aquarium tanks.

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BACKGROUND AND OBJECTIVES: Increasing urbanization and the aging global population highlight cities as vital environments for promoting healthy aging. However, the relationship between characteristics of urban green spaces and older adults' mental well-being remains unclear.

Cellular morphological changes occur during cell life and diseases, such as senescence and cancer. Although the cellular conditions should be varied with the morphology changes, there have been no attempts to understand the cellular morphological changes by focusing on the intracellular molecular environment and elucidating the behaviour of nucleic acids. Nucleic acids can form hierarchical secondary and higher-order structures due to intermolecular interactions and other factors. Additionally,...

Ribosomal DNA (rDNA) encodes the 18S, 5.8S, and 28S rRNA, accounting for ∼70% of cellular transcription. Despite its essential role and links to cancer and aging, quantifying rDNA instability in mammals remains challenging due to its repetitive organization and inherent heterogeneity. Here, we developed a murine rDNA FISH probe and genomic tools tailored for laboratory mouse strains. The results confirmed rDNA cluster locations, revealed substantial inter- and intra-strain as well as...

Cancer cells precisely modulate replication stress to sustain genomic instability without triggering lethal DNA damage, yet regulators enabling this delicate balance remain largely unknown. Here, we identify N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF) as a novel and critical regulator of replication stress in colorectal cancer (CRC). NSMF expression is significantly elevated in CRC tissues and correlates closely with elevated replication stress. In...

Aging is accompanied by profound changes in energy metabolism, yet the underlying drivers and modulators of these shifts remain incompletely understood. Here, we investigated how life-history evolution shapes metabolic aging and pharmacological responsiveness by leveraging Drosophila melanogaster lines divergently selected for reproductive timing. We measured organismal oxygen consumption rate and performed untargeted metabolomics in young and old flies of both sexes from long-lived "O" lines...

Immune cells from the skull marrow reach the meninges through bone channels. In this issue of Immunity, Eme-Scolan and colleagues show that these channels form neonatally and can be remodeled to alter immune access to the brain's borders. Their work suggests that the skull is a developmental checkpoint for neuroimmune defense, potentially shaping vulnerability or resilience across the lifespan.

Dual-task walking, performing a secondary task while walking, challenges attentional and motor resources and has been linked to increased fall risk. While cognitive dual tasks are most often studied, physical (e.g., load carriage) and "combination" tasks such as obstacle crossing may also impact gait. Whole-body angular momentum and its variability provide sensitive markers of locomotor stability. We investigated how dual-task type influences gait mechanics and stability in younger and older...

CONCLUSIONS: These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.

Rechargeable zinc metal batteries are promising for large-scale energy storage due to their low cost and high safety, but their development is seriously hindered by the dendritic growth and side reactions of zinc metal anodes. To address this challenge, we report here that rational design of low-surface-tension electrolytes can enable dense nucleation and fine-grained growth of zinc. This low-surface-tension strategy leads to high stability of the solid-electrolyte interface, dendrite-free...

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Senescent cell accumulation contributes to aging, and their clearance represents an effective anti-aging strategy. Current senolytic strategies focus on drug-mediated senescent cell clearance, but it is unknown whether a hypobaric condition can induce senescent cell death. Here we show that hypobaric pressure (HP) at -375 mmHg without hypoxia induces cells to undergo lysosome-dependent cell death (LDCD). Mechanistically, we unveil that HP activates transmembrane protein 59 (TMEM59) to induce...

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Disease tolerance is a defence strategy essential for survival of infections, limiting physiological damage without killing the pathogen^(1,2). The disease course and pathology an infection may cause can change over the lifespan of a host due to the structural and functional physiological changes that accumulate with age. Because successful disease tolerance responses require the host to engage mechanisms that are compatible with the disease course and pathology caused by an infection, we...

Age-related decline in physical function is a hallmark of aging and a major driver of morbidity, disability, and loss of independence in older adults, yet the molecular processes linking muscle aging to functional deterioration remain incompletely defined. Emerging evidence implicates ferroptosis, defined as iron-dependent, lipid peroxidation-driven cell death, as a compelling but underexplored contributor to age-related muscle wasting and weakness. Although ferroptosis signatures appear in aged...