Aging & Longevity

Aging and obesity are associated with pro-inflammatory changes in adipose tissue. Overlapping mechanisms, such as the infiltration of inflammatory macrophages and T cells into visceral adipose tissue, have been implicated in contributing to inflammation. However, a comparative analysis of both states is needed to identify distinct regulatory targets. Here, we performed single-cell RNA sequencing of stromal vascular fractions (SVF) isolated from gonadal white adipose tissue (gWAT) of young mice...

Caloric restriction (CR) with fasting extends lifespan but is difficult to maintain in humans. Here, we compared conventional CR with periods of fasting to an ad libitum-fed low-protein, high-carbohydrate (LPHC) diet diluted 25% with non-digestible fibre. Both approaches similarly enhanced longevity and metabolic health in mice relative to a control diet. Proteomic analysis of liver tissue revealed that CR increased proteins associated with energy and mitochondrial pathways. By contrast, the...

Fasting-based interventions are gaining momentum as strategies to modulate longevity. Conversely, the same metabolic adaptations that once ensured survival during starvation now contribute to the global obesity epidemic. While previous studies have characterized metabolic changes during fasting, few have examined the refeeding phase, and most lack an integrated analysis of key hormonal and metabolic regulators, including insulin, leptin, adiponectin, free T3, FGF21, and the plasma metabolome. To...

Emerging evidence has revealed a strong association between obstructive sleep apnea (OSA) and aging. Considering the critical role of the cardiovascular system, this review explores the key mechanisms linking OSA to cardiovascular aging through a focus on chronic intermittent hypoxia (CIH) -induced oxidative stress and chronic inflammation. Specifically, we examine six key pathways: (1) cellular senescence, (2) mitochondrial dysfunction, (3) metabolic dysregulation, (4) telomere attrition, (5)...

Chronic hypertension with aging induces significant alterations in the structure and function of brain parenchyma and memory dysfunction. While therapeutic control of hypertension reduces risk, the functional changes in neural circuitry that underlie memory deficits are unknown. Identifying possible early onset changes in the hippocampal trisynaptic circuit (HTC) may reveal opportunities for therapeutic intervention. A large-scale clinical study revealed a direct relationship between reduced...

Myeloid-biased differentiation of multipotent hematopoietic stem and progenitor cells (HSPCs) occurs with aging or exhaustion. The molecular mechanism(s) responsible for this fate bias remain unclear. Here, we report that linker histone regulates HSPC fate choice at the lymphoid versus myeloid bifurcation. Linker histones package nucleosomes and compact chromatin. HSPCs expressing a doxycycline (dox)-inducible H1.0 transgene favor the lymphoid fate, display strengthened nucleosome organization,...

Recent advances in single-cell transcriptomics have led to the identification of disease-associated microglia (DAM) as a distinct, conserved microglia state associated with mouse models of Alzheimer's disease (AD) and amyotrophic lateral sclerosis, and with aging. DAM are characterized by downregulation of homeostatic genes and upregulation of lipid metabolism and phagocytosis genes, including key risk factors for AD in humans. Although characterized in models of AD, whether DAM acts as...

CONCLUSIONS AND IMPLICATIONS: This systematic review and meta-analysis identified and quantified the risk factors associated with impaired IC, which will facilitate the creation of targeted interventions aimed at preventing impaired IC and lessening its adverse effects on health. Quantitative analysis is still needed with additional studies in the future. Targeted prevention approaches should mitigate IC impairment by focusing on the modifiable risk factors.

Reproduction affects lifespan and fat metabolism across species, suggesting a shared regulatory axis. In Caenorhabditis elegans, ablation of germline stem cells leads to extended lifespan and increased fat storage. While many studies focus on germline-less glp-1(e2144) mutants, the hermaphroditic germline of C. elegans provides an excellent opportunity to study how distinct germline anomalies affect lifespan and fat metabolism. We compare metabolomic, transcriptomic, and genetic pathway...

Hematopoietic stem cells (HSC) sustain lifelong blood and immune system homeostasis. This study identifies P-selectin as a pivotal regulator of HSC function under aging and inflammatory stress. We observed pronounced Selp upregulation in aged HSC and inflammatory contexts, which drives excessive proliferation and differentiation while depleting their long-term self-renewal capacity. Using tissue-specific Selp overexpression models, we demonstrate that chronic Selp elevation disrupts HSC...

Declining mitochondrial function is an established feature of aging and contributes to most aging-related diseases through its impact on various pathologies such as chronic inflammation, fibrosis and cellular senescence. Our recent work suggests that benign prostatic hyperplasia, which is an aging-related disease frequently associated with inflammation, fibrosis and senescence, is characterized by a decline in mitochondrial function. Here, we utilize glycolytic restriction and pharmacologic...

CONCLUSIONS: A negative eGFR(diff) (eGFR(cys)-eGFR(cr) < -15 mL/min/1.73m²) was associated with a higher risk of dementia, poorer cognitive functions, and worse biological age acceleration. While those with a positive eGFR(diff) had a lower risk.

Aging biomarkers play a vital role in understanding longevity, with the potential to improve clinical decisions and interventions. Existing aging clocks typically use blood, vitals, or imaging collected in a clinical setting. Wearables, in contrast, can make frequent and inexpensive measurements throughout daily living. Here we develop PpgAge, an aging clock using photoplethysmography at the wrist from a consumer wearable. Using the Apple Heart & Movement Study (n = 213,593 participants; >149...

CONCLUSION: Molecular signatures underlying regional vulnerability to AD provide a framework for understanding genetic and systemic factors in disease progression. Findings highlight specific molecular pathways, including ECM-related processes and hormonal regulation, as key drivers of susceptibility. Finally, identified drug repurposing candidates present promising therapeutic avenues for further investigation.

While the health effects of dietary copper intake have been widely studied, no research to date has specifically examined its association with biological aging. Here, we aim to explore the relationship between dietary copper intake and biological aging, while examining the mediating role of dietary inflammatory index (DII). This cross-sectional study included 18,160 adults from the 2003 to 2018 National Health and Nutrition Examination Survey (NHANES). Weighted multivariable linear regression...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a fatal genetic disorder caused by progerin, a mutant lamin A variant that disrupts nuclear architecture and drives systemic cellular dysfunction. Gastrointestinal (GI) involvement in HGPS remains poorly understood, despite growing evidence of gut abnormalities and microbial dysbiosis in progeroid mouse models. Here, we provide the first comprehensive characterization of colonic pathology in Lmna^(G609G/G609G) mice and assess the therapeutic impact...

The advent of in vivo reprogramming through transient expression of the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC) holds strong promise for regenerative medicine, despite ongoing concerns about safety and clinical applicability. This review synthesizes recent advances in in vivo reprogramming, focusing on its potential to restore regenerative competence and promote rejuvenation across diverse tissues, including the retina, skeletal muscle, heart, liver, brain, and intestine. We highlight...

CONCLUSIONS AND IMPLICATIONS: This review and meta-analysis support that exercise training is an effective model of improving frailty levels among older adults in long-term care. Strategies to address the practical aspects of these programs are needed, but this study emphasizes that structured exercise should be a crucial aspect of long-term care.

CONCLUSIONS AND IMPLICATIONS: Our findings highlight the clinical importance of recognizing fatigue throughout the entire aging life span as an independent marker for subsequent negative health outcomes and mortality. Although fatigue might serve as a surrogate for intrinsic capacity, it remains unclear if fatigue is amenable to intervention.

Age-related decline in motor control, manifesting as impaired posture, gait, and slowed movement execution, significantly diminishes the quality of life in older adults. These functional deficits are associated with alterations in neurophysiological data, which are analyzed using advanced techniques including spectral analysis, complexity measures, and functional connectivity network analysis. These methodologies provide valuable insights into the neurobiological mechanisms underpinning...