Aging & Longevity

CONCLUSIONS: In the multimorbidity management model for older adults, interventions such as patient peer support groups and case manager-led health education are proposed as theoretical strategies. These potential measures aim to support patient self-efficacy and facilitate health literacy, thereby potentially contributing to better overall health of patients.

CONCLUSIONS: There are distinct joint trajectories of physical frailty and social relationships among Japanese community-dwelling older adults. These trajectories are associated with different risks of long-term care needs, with the progressive frailty and rapid social relationships decline subgroup facing the greatest burden.

Macrophages are pivotal immune cells due to their phagocytic capabilities, yet the impact of aging on macrophage phagocytosis remains poorly understood. Using comprehensive in vitro and in vivo phagocytic assays, we demonstrate significantly reduced phagocytic activity in monocyte-derived macrophages from aged humans and mice compared to young counterparts. RNA-seq analysis revealed upregulated expression of extracellular matrix protein genes, particularly collagens, in aged macrophages;...

Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various...

Aging tissues experience a gradual decline in perfusion and metabolic resilience due to complex interactions among extracellular matrix (ECM) remodeling, vascular dysfunction, and mitochondrial impairment. Stiffening of the ECM that results from collagen crosslinking, elastin loss, and basement membrane thickening reduces vascular compliance and impairs local angiogenesis. The consequent reduction in capillaries and diminished endothelial reactivity leads to ongoing or intermittent hypoxia,...

Quantitative insights into brain metabolism are essential for advancing our understanding of the energy dynamics in the brain. Here, we present a nanowatt-resolution biocalorimeter capable of real-time metabolic heat output measurements of individual, live Drosophila melanogaster brains. Using this platform, we show that female brains, across multiple genotypes, exhibit a significantly higher metabolic rate (∼10%-15%) than male brains at a young age (<10 days old) and follow distinct metabolic...

Aging is the primary risk factor for most chronic diseases, and the global rise in aging populations presents an escalating challenge due to functional decline and multimorbidity. Gene therapy provides a versatile framework for modulating aging-regulatory pathways, such as epigenetic regulation, telomere maintenance, and stress-response networks, with the potential to reshape aging trajectories. In this review, we provide an in-depth synthesis of the genetic and epigenetic determinants of aging...

The human immune system undergoes dynamic remodeling from infancy through old age. We profiled PBMCs from 167 healthy individuals (ages 2 months to 105 years): infants (n = 36), children (n = 26), adolescents (n = 20), young adults (n = 24), middle‑aged (n = 16), older adults (n = 33) and oldest old (n = 12) using scRNA‑seq and snATAC‑seq (n = 23). MAIT and γδ T cells showed a "rise and fall" pattern, rising in childhood, peaking in young adulthood, and declining with age. Conventional CD8⁺ T...

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more...

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular 'clocks' to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

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The brain and body undergo coordinated changes throughout the life span, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to aging and peripheral biomarkers of metabolic and vascular function, including body mass index, blood pressure, and blood biochemistry. We use multivariate pattern learning to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and...

Hypoxia is a common stress encountered by animal tissues during development, physiology, and disease. To cope with hypoxic stress, cells remodel metabolic and signaling networks to preserve viability and function. Lysosomes serve as central hubs for metabolic control and intracellular signaling, yet their role in hypoxic adaptation remains unclear. Here, we identify the lysosomal calcium transporter TMEM165 as a hypoxia-responsive regulator of cellular homeostasis. Under hypoxic conditions,...

ObjectivesThis study examined the influence of hearing status and loneliness on verbal fluency trajectories in adults aged 60 years and older, assessing their contributions to baseline performance and longitudinal change over time.MethodsData were drawn from 4,929 participants in the Health and Retirement Study (HRS) with objective hearing assessment in 2018 and three waves of semantic verbal fluency and loneliness measured in 2018, 2020, and 2022. Latent growth curve models were estimated to...

Chronic intestinal inflammation establishes a pro-senescent microenvironment that fuels the stepwise evolution from inflammatory bowel disease (IBD) to colorectal cancer. Although cellular senescence initially functions as a tumor-suppressive barrier, the persistent accumulation of senescent cells can promote disease progression through the senescence-associated secretory phenotype (SASP). Key SASP mediators, including VEGF, IL-8/CXCL8, and matrix metalloproteinases (MMPs), reprogram endothelial...

Chronic moderate aerobic exercise promotes health in older adults and provides neuroprotection to patients with neurodegenerative diseases, most notably Parkinson's disease (PD). Exosomes are small extracellular vesicles that facilitate interorgan communication. During exercise, they are selectively packaged with bioactive molecules termed "exerkines" and released into the blood. Exosomes protect their exerkine cargo, including DNA, RNA, and proteins, and facilitate their interorgan transit....

As the global population ages, effective strategies to attenuate or prevent neurodegenerative processes are becoming increasingly important. Gerobiotics, an emerging class of probiotic strains and their derived postbiotics, are considered promising geroprotective agents because of their potential to target fundamental mechanisms of aging, modulate the gut-brain axis, and attenuate age-related cognitive and functional decline. This review aims to synthesize existing evidence from preclinical and...

CONCLUSION: Plasma SVIP demonstrates significantly higher diagnostic accuracy than VCP for the detection of aMCI, suggesting its potential as a candidate blood-based biomarker pending large-scale pathophysiological validation.