Aging & Longevity

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Brain maintenance may help explain why some individuals remain cognitively resilient despite aging, but its biological basis is not well understood. Here, we show that brain maintenance can be quantified from the relationship between brain structure and function. Using structural MRI and resting-state functional MRI from 1280 older adults, we built a model based on young adults to estimate the functional capacity supported by preserved brain structure, and defined brain maintenance as the...

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CONCLUSIONS: Higher RC levels were consistently associated with more advanced biological aging across two populations and two clinical aging metrics. These findings support RC as a clinically accessible marker associated with adverse biological aging profiles.

Ageing and interventions modulate health and mortality¹, yet the underlying molecular mechanisms of this modulation remain unclear. Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age and expected mortality, predicting lifespan-modulating interventions, time to death, chronic diseases and rejuvenation. Ageing-related changes were...

Accumulation of mutant mitochondrial DNA (mtDNA) heteroplasmy is among the strongest signatures of ageing¹. Here we investigated the underlying mechanism by calling mtDNA sequence, mtDNA abundance and mtDNA heteroplasmic variants in human blood using whole-genome sequences from approximately 750,000 individuals. We observed that mtDNA single-nucleotide variants (mtSNVs) accumulate sharply at age 60 years, occur at low levels of heteroplasmy, exhibit little evidence of positive selection and are...

Inflammation activates blood cells, contributing to ageing and malignancy^(1-3). Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis^(1-9), but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation-recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were...

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.