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An experimental compound called AP503 significantly strengthened bones in mice by activating GPR133, a receptor that boosts bone formation while slowing bone loss. Because the same treatment has also been linked to stronger muscles, researchers see intriguing potential for combating age-related decline and osteoporosis.

Semaglutide, the drug found in Ozempic and Wegovy, was linked to nearly 40% fewer asthma attacks in a large real-world study. It was also associated with about 20% fewer COPD flare-ups. Researchers say GLP-1 drugs may offer respiratory benefits in addition to their effects on diabetes and obesity, but clinical trials are needed to confirm the findings.

The first arm bone fragment from these mysterious human relatives was found near cutting instruments and animal remains in southwestern China

CONCLUSIONS AND IMPLICATIONS: Rural nursing homes exhibited disaster resilience under baseline disaster conditions but not during evacuation. It is possible that evacuation exposes rural nursing home residents to structural and operational constraints that may differentially compromise postdisaster survival. Future federal and state guidance may benefit from aligning preparedness standards with the distinct constraints of rural nursing homes.

Cellular senescence is one of the best-studied biological programs, yet it continues to reveal unexpected aspects. In this issue of Developmental Cell, Durik et al.¹ describe how senescent cells shed large cytoplasmic fragments that promote their survival and may represent a mechanism of communication with neighboring cells.

Somatic mutations accumulate throughout life in every cell, and this process constitutes one of the hallmarks of aging-genomic instability. Caloric restriction (CR) has been shown to extend lifespan across diverse species. Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes, and cerebellar neurons, we found that CR in mice reduces genome-wide somatic mutation burdens across multiple tissues and cell types. CR reduced both substitution and insertion/deletion burdens,...

Current brain atlases are largely descriptive, cataloging correlative molecular snapshots such as gene expression signatures yet offering limited functional insight. Here, we develop a scalable, cell-type-resolved in vivo CRISPR interference (CRISPRi) platform enabling systematic gene function profiling in the mouse brain. Through genome-wide screens across four neuronal populations at three time points spanning youth to aging, we identify neuronal essential genes missed in vitro and define a...

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disorder characterized by marked clinical heterogeneity and incompletely understood genotype-phenotype correlations. While X-chromosome inactivation has been extensively investigated, the contribution of autosomal epigenetic mechanisms to phenotypic variability remains poorly defined. Here, we performed an exploratory genome-wide DNA methylation analysis in 32 AFD patients (22 females and 10 males; mean age 51.7 years) recruited...

GAIP-interacting protein C-terminal 1 (GIPC1/GIPC) is a well-established protein in the field of cancer biology. Recent studies have revealed that GIPC1 may exert opposing, context-dependent functions in various diseases or physiological processes, although the underlying regulatory mechanisms remain to be explored. Since GIPC1 contains a PDZ domain that interacts with various proteins, this domain is a promising therapeutic target. Molecular probes designed against the GIPC1-PDZ domain could...

As the body ages, chronic low-grade inflammation, metabolic dysregulation, and loss of tissue resilience occur; however, the pathways linking these processes have not been fully characterized. Beyond traditional host defence, the canonical complement C3a-C3AR1 signalling axis has been identified as an ageing-sensitive pathway. Studies involving naturally aged animals, older human cohorts, and models of age-related diseases indicate that chronic C3a-C3AR1 signalling can drive the reprogramming of...

The evolutionary biology of aging is fundamental to understanding the mechanisms of aging and how to develop anti-aging treatments. Thus far most evolutionary theory concerns the genetics of aging with limited physiological integration. Here we present an intuitive evolutionary framework built on how physiology is regulated and how this regulation itself ages. Life has evolved to secure reproduction and avoid system failure in early life, and it is the regulation that evolves in response to...

Yu and colleagues¹ demonstrate that α-synuclein pathology within the dorsal motor nucleus of the vagus (DMV) compromises neuronal excitability and drives Parkinson's disease-related gastrointestinal dysmotility through alteration of a fundamental DMV-gut circuit. Electroacupuncture reactivates this circuit ameliorating this functional deficit.

Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their...

Proteins generally begin with methionine, which is often removed to expose the second residue. RuBP carboxylase/oxygenase (Rubisco), the most abundant enzyme on Earth and a major carbon and nitrogen reservoir, escapes this paradigm. Its catalytic subunit, RbcL, undergoes unusual amino terminal maturation, including atypical initiator methionine-serine cleavage and proline acetylation, a modification not seen in other biological systems. We define a specialized pathway of two sequential...

ObjectiveThis study examines how life expectancy (LE) without and with depression differs by living arrangement among older adults in Japan, with particular attention to gender differences.MethodsData were drawn from the Nihon University Japanese Longitudinal Study of Aging (1999-2009). Multistate life table methods were used to estimate LE spent without and with depression among adults aged 65 years and older across different living arrangements.ResultsPronounced gender differences were...

This year's Lasker~Bloomberg Public Service Award honors the singular achievement of Michael J. Fox, who has devoted much of his life to a philanthropic effort to conquer Parkinson's Disease (PD), a progressive neurodegenerative disorder that afflicts many millions of patients world-wide. Just a few years after his diagnosis of PD at the tender age of 29, Fox pivoted in part from his enormous success in acting [leading roles in the Back to the Future trilogy (1985-1989) and in the hit National...

Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD). However, their clinical application is constrained by replicative aging during in vitro expansion. In this study, we investigated whether a three-dimensional (3D) Matrigel-based culture system could modulate replicative aging in LNCs. Compared with conventional two-dimensional...

Bone marrow-derived macrophages were shown to play an important role in coping with Alzheimer's disease (AD). Boosting their spontaneous recruitment reduces inflammation and disease pathology and slows cognitive decline in mouse models of amyloidosis. However, the factors limiting their spontaneous homing to the diseased brain remain unclear. In this study, we discovered that monocyte development is impaired in mouse models and in patients. In the 5×FAD mouse model, monocyte differentiation was...

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