Aging & Longevity

During aging, microglia - the resident macrophages of the brain - exhibit altered phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model...

Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O(2peak)) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We...

Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status. In this prospective UK Biobank study, BA acceleration was measured using the Klemera-Doubal method BA (KDM-BA) and Phenotypic age (PhenoAge). Cox models estimated associations of BA acceleration with incident T2D (n = 271,885) and CAD (n = 270,054). Both additive and multiplicative interactions between BA acceleration and polygenic risk score (PRS) were examined. Predictive performance was...

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CONCLUSIONS: Postural imbalance is a common occurrence in a vulnerable older population in Brazil. Importantly, we found that depressive symptomatology was associated with increased odds of having postural imbalance and postural imbalance with falls experienced in the previous 6 months. Notwithstanding our analyses' exploratory nature, these issues should receive greater attention in primary care practice and research.

Aging is a universal biological process that impacts all tissues, leading to functional decline and increased susceptibility to age-related diseases, particularly cardiometabolic disorders. While aging is characterized by hallmarks such as mitochondrial dysfunction, chronic inflammation, and dysregulated metabolism, the molecular mechanisms driving these processes remain incompletely understood, particularly in a tissue-specific context. To address this gap, we conducted a comprehensive...

DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis...

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CONCLUSIONS: This study highlights that HCBS have not been fully utilised and are influenced by various factors. Moving forward, it is crucial to address the care needs of different income groups, with particular attention to the unique challenges faced by rural older adults. Targeted policies and interventions are necessary to enhance accessibility for those with chronic illnesses and limited family support. Local governments should work in partnership with families to develop higher-quality,...

The quality and quantity of the ovarian reserve are meticulously regulated through various cell death pathways to guarantee the availability of high-quality oocytes for fertilization. While apoptosis is recognized for contributing to maintaining ovarian reserve, the involvement of other cell death pathways remains unclear. Employing chemical genetics and proteomics, this study reveals the crucial involvement of Cathepsin B in maintaining the ovarian reserve. Results indicate that apoptosis and...

CONCLUSION: Decomposing the power spectrum into periodic and aperiodic components allows for the characterization of age-related changes.

Immune resilience as a salutogenic force to preserve healthspan and resilience to challenges. The figure was created with BioRender (https://www.BioRender.com/).

Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against...

CONCLUSIONS: The frailty index was cross-sectionally associated with EAA, while only GrimAge and DunedinPoAm38 EAA predicted changes in the frailty index. More research is needed to understand the interplay between pathways.

Postmenopausal women often experience fatigue and mood disturbance both of which interfere with quality-of-life. Since greater physical function aids psychosocial well-being, we hypothesized the acute cardiopulmonary responses during walking may reveal important factors linked to fatigue and mood disturbance. In this cross-sectional study, women of similar body mass index (BMI) aged 55-75 y were dichotomized to mid-life (55-65 y; 83.4 ± 8.4 kg/m²; n = 14) or older (≥65 y; 81.8 ± 10.4 kg/m²; n =...

Changes in the proteome and its dysregulation have long been known to be a hallmark of aging. We derived a proteomic aging trait using data on 1459 plasma proteins from 44,435 UK Biobank individuals measured using an antibody-based assay. This metric is strongly associated with four age-related disease outcomes, even after adjusting for chronological age. Survival analysis showed that one-year older proteomic age, relative to chronological age, increases all-cause mortality hazard by 13 percent....

Incidence of colorectal cancer (CRC) is increasing likely due to different mechanisms driving initiation and progression. The initial model proposed by Fearon and Vogelstein posits it as a multi-hit neoplasia, originating from adenomatous-polyps induced by WNT activation, ultimately progressing to aggressiveness through p53 loss. Integrating human data with mouse genetics, we redefine this paradigm, highlighting pivotal roles of MYC, oncogenic URI and p53 degradation to initiate CRC. Early APC...

The large variety of inflorescence architectures evolved in grasses depends on shape, longevity and determinacy of meristems directing growth of the main and lateral axes. The CLAVATA pathway is known to regulate meristem size and inflorescence architecture in grasses. However, how individual meristem activities are determined and integrated to generate specific inflorescences is not yet understood. We found that activity of distinct meristems in the barley inflorescence is controlled by a...

CONCLUSIONS: A valid and reliable 17-item community-level indicator was developed, aligning with the WHO framework and incorporating dementia-friendly elements. This indicator is a valuable tool for monitoring, evaluation, and inter-community comparisons, aiding the development of AFCs and DFCs in aging societies like Japan. Additionally, this indicator can be adapted for other high-income countries with similar socioeconomic backgrounds, healthcare systems, and community structures, providing a...

Age-related skeletal muscle atrophy, known as sarcopenia, is characterized by loss of muscle mass, strength, endurance, and oxidative capacity. Although exercise has been shown to mitigate sarcopenia, the underlying governing mechanisms are poorly understood. Mitochondrial dysfunction is implicated in aging and sarcopenia; however, few studies explore how mitochondrial structure contributes to this dysfunction. In this study, we sought to understand how aging impacts mitochondrial...