Aging & Longevity

Normative models of brain metrics based on large populations could be extremely valuable for detecting brain abnormalities in patients with a variety of disorders, including degenerative, psychiatric and neurodevelopmental conditions, but no such models exist for the brain's white matter (WM) microstructure. Here we present a large-scale normative model of brain WM microstructure - based on 19 international diffusion MRI datasets covering almost the entire lifespan (totaling N = 54,583...

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Hypothalamic POMC neurons modulate systemic energy balance and glucose homeostasis by sensing nutritional state signals. In addition to this classic regulatory mode, these neurons are also activated by the sensory perception of food. Here, we report that food-related sensory cues engage glycogen metabolism in POMC neurons. Genetic depletion of glycogen through various approaches renders POMC neurons unresponsive to food-associated sensory stimuli. This defective perception of food is linked to...

Classifying ovaries solely as reproductive organs has obscured their role as systemic regulators of female physiology. This Perspective makes the case that ovarian aging is a primary determinant of healthspan and belongs at the center of geroscience.

Aged skeletal muscle has a diminished capacity to recover after disuse. Although muscle regrowth requires coordinated interactions between immune and progenitor cells, the mechanisms of impaired remodeling in aged skeletal muscle remain poorly understood yet possibly involve the accumulation of senescent cells. We used a flow cytometry approach coupled with scRNAseq to determine the muscle senescent cell identity and transcriptional landscape during skeletal muscle recovery following disuse...

Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP....

Senescence and immortality are central biological paradigms. While regenerative capabilities in Deuterostomia are known, the fate of lost and discarded tissues has been presumed terminal. Here, we demonstrate that explanted epidermal, connective, neural, and muscle tissue from the sea cucumber Psolus fabricii (Holothuroidea: Echinodermata) healed and continued to grow in natural, nonaxenic seawater without supplementation for more than 3 years. In experimental trials, these explants, termed...

CONCLUSION: Both pain severity and pain interference were significantly associated with cognitive impairment after adjustment for key confounders. These findings highlight the importance of addressing pain's impact on daily functioning to mitigate cognitive decline in this population.

CONCLUSIONS: Given its significant public health implications, targeted interventions are essential to reduce food insecurity and its associated health burden, ultimately improving longevity and quality of life among aging populations.

As the challenges posed by an aging population become increasingly apparent, the prevention and treatment of age-related diseases have become key research priorities. This study hypothesizes that Zhizi Baipi Decoction exhibits aging modulatory effects. Traditional Chinese Medicine Decoction that has been passed down for generations and remains widely used in contemporary clinical practice. Due to their short lifespan, well-defined genetic backgrounds, and ease of manipulation, model organisms...

While mitochondria are recognized as promising therapeutic targets for common pathologies of aging, existing drug discovery platforms fail to capture the adequate physiological and biological contexts necessary to identify translatable, clinically-relevant leads. The goal of this study was to identify marine natural products that modulate mitochondrial function using a screening pipeline leveraging primary human cells in a cell-based phenotypic primary screen. Using this approach, we identified...

The anterior cingulate cortex (ACC) is particularly vulnerable to aging, which impairs cognitive functions such as attention and working memory. Although aging is known to alter intrinsic electrophysiological properties in other brain regions, the differences in the properties of aged ACC neurons and young adult neurons remain uninvestigated. In this study, we compared the intrinsic membrane properties and firing characteristics of aged layer 2/3 pyramidal neurons (26-month-old rats) with those...

CONCLUSION: These results show the impact of food insecurity and functional limitations and HRQOL in older adults. The results emphasize the urgent need for addressing food insecurity and promote healthy aging among older adults in New York City.

Young children are at increased risk for respiratory tract infections and are frequently colonized by respiratory pathogens. However, how the mucosal immune system differs between children and adults is relatively unknown. We collected nasal samples from 50 young children (aged 1-5 years) and 318 young adults (aged 18-34 years) to study how the mucosal immune system and host-microbe interactions differ with age. We used multi-omics data integration to combine host (immunophenotyping,...

Globally, the growing proportion of older individuals is imposing personal and societal costs. However, interventions that slow aging are possible; for example, dampened nutrient signaling pathway activity in animal models promotes better health later in life. Recent findings indicate that such interventions have long-term effects even when applied transiently in early adulthood, forming a "physiological memory." Similar memory has been extensively documented in human epidemiology, where the...

Aging is typically framed as a one-way, irreversible accumulation of molecular damage in cells and tissues, leading to progressive functional decline. Yet mammalian reproduction, and particularly female reproduction, reveals a striking exception to this rule. Despite residing within an aging organism and within a fast-aging ovarian tissue environment, oocytes give rise to embryos that begin life with restored developmental potential and youthful molecular organization. By reframing ovarian...

Maintaining balance requires a complex interplay between sensory and motor processes, and this ability deteriorates with age, impairing daily life activities and contributes to increased fall risks. Importantly, while cognitive-motor interference paradigms suggest an aging-related increase in the cortical involvement in balance regulation, direct evidence remains lacking. To clarify this issue, we assessed the effect of aging on sway-based corticokinematic coherence (CKC), which is a measure of...

Endogenous bioelectric currents regulate development and regeneration, but their influence on organismal longevity and stem cell-mediated repair is not well understood. We demonstrate that a brief, clinically safe pulse of electrical current (PEC) produces lasting rejuvenation in the colonial chordate Botryllus schlosseri. In this species where all differentiated tissues are replaced weekly and progenitor populations mediate the weekly de novo generation of new organs, organismal aging is...

The mitochondrial unfolded protein response (UPR^(mt)) protects mitochondria from proteotoxic stress. Current models induce acute and severe mitochondrial disruption and propose cytosolic detection following the release of mitochondrial damage signals into the cytosol. However, this mode of toxicity contrasts sharply with physiological stress, such as the gradual accumulation of reactive oxygen species (ROS) during aging or chronic respiratory chain defects. Here, we employ a chemogenetic...

Haematopoietic stem cells (HSCs) produce all blood and immune cells throughout life, but ageing progressively impairs their function, generating excessive myeloid and megakaryocyte cells at the expense of lymphocytes. This lineage imbalance contributes to immune decline, chronic inflammation and increased disease susceptibility in the elderly, yet the underlying mechanisms remain poorly understood. Here we show that a specific Meg3^(+) HSC subset...