Aging & Longevity

Somatic mitochondrial DNA (mtDNA) mutations are implicated as important drivers of ageing and age-related diseases. Their pathological effect can be counteracted by increasing the absolute amount of wild-type mtDNA via moderately upregulating TFAM, a protein important for mtDNA packaging and expression. However, strong TFAM overexpression can also have detrimental effects as it results in mtDNA hypercompaction and subsequent impairment of mtDNA gene expression. Here, we have experimentally...

A stable caregiving environment early in life is essential for children's development, and disruptions have the potential to impact biological processes. Using data from the Bucharest Early Intervention Project, we examined a developmental cascade model in which shifts in pubertal tempo following early caregiving disruptions come at an epigenetic cost. Among 115 individuals, all of whom experienced severe deprivation early in life, we tracked caregiving disruptions across childhood; assessed...

BackgroundSocial frailty has not been studied in the Philippines, a Southeast Asian country with distinct sociocultural characteristics.ObjectiveTo (i) develop and validate the Social Frailty Index-Philippines (SFI-Phil), using all-cause mortality (up to 4 years) as the outcome and (ii) evaluate performance of SFI-Phil across age, sex, and residence.MethodsPerforming regression analyses on baseline and 4-year follow-up data from 5153 older adults aged 60+ from the nationally representative...

INTRODUCTION: Osteoarthritis (OA), a prevalent musculoskeletal condition, is associated with an increased risk of falls. Maintaining posture relies on visual, vestibular, and proprioceptive inputs, but these systems can be compromised due to aging or disease, heightening fall risk. Such impairments may result from neuromuscular decline and reduced cognitive or visuospatial processing abilities. This study aimed to investigate prefrontal cortical (PFC) activation patterns during clinical sensory...

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature aging and primarily caused by the accumulation of progerin, a mutant form of lamin A. Although the effects of progerin on multiple tissues have been previously studied, its impact on brain development is not completely understood. We established cortical organoids derived from HGPS patient-induced pluripotent stem cells (iPSCs) from patients with HGPS to investigate the role of progerin in the...

CONCLUSION: The association between the TG/HDL-C ratio (atherogenic index) and incident ASCVD steadily attenuates with age. In adults over 65, an elevated ratio may be associated with a lower risk of incident ASCVD. These findings may reflect changes in metabolic atherosclerotic risk or a survival effect associated with aging and require further investigation.

Cognitive decline associated with healthy ageing is multifactorial: brain-based and lifestyle factors uniquely and jointly contribute to distinct neurocognitive trajectories of ageing. To evaluate existing models of neurocognitive ageing such as compensation, maintenance, or reserve, we explore how various known brain-based and cardiorespiratory fitness factors intersect to better understand cognitive decline. In a pre-registered study (https://osf.io/6fqg7), we tested 73 healthy older adults...

The rhesus macaque presents a promising model for translational research into human brain aging due to this species' long lifespan and close phylogenic relationship. We conducted a cross-sectional study identifying microstructural and morphological biomarkers of aging in a cohort of 37 healthy animals (18F/19M, aged 5-28 years), using high-resolution T2-weighted (T2w) and diffusion-weighted (DW) images. Using Tensor Based Morphometry, significant age-associated regional brain atrophy was...

Metformin is the most commonly prescribed glucose-lowering agent worldwide for the treatment of type II diabetes. Due to evidence of improvements in healthspan and lifespan in model organisms, and mechanistic data relevant to the hallmarks of aging, it has been considered a promising candidate in the search for pharmacological interventions that may attenuate the ageing process in humans. Various epidemiological studies have been influential in generating support for this hypothesis. These...

COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific...

Influenza poses a significant threat to older adults, exacerbated by age-related immune decline and the high prevalence of chronic conditions. Despite being the most effective preventive measure, influenza vaccination rates among this population remain alarmingly low, with Italy and Europe failing to meet the World Health Organization’s target of 75% coverage for individuals aged 65 and over. This review, informed by a geriatric conference in Enna, Sicily, examines the epidemiology of influenza...

Lifespan is a highly variable life trait across the Tree of Life, governed by complex and multifactorial mechanisms. While some conserved pathways regulating longevity have been identified in various species, the molecular basis of this phenotype is far from being understood. In this context, the adoption of new model species and methods of investigation may offer opportunities to explore the molecular underpinnings of longevity in animals. In this study, we investigated the genomic resources of...

CONCLUSIONS: Those aged > 70, at risk of malnutrition, and having dementia had higher odds of sarcopenia. In contrast, having an educational level of a diploma or lower, ≥ one session of physical activity per week, and having hypertension showed a reverse association with sarcopenia. Findings underscore the importance of targeted interventions to mitigate sarcopenia risk in aging populations.

Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months...

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Cytochrome b(5) reductase 3 (CYB5R3) overexpression mimics several metabolic benefits of calorie restriction, with sex- and tissue-specific effects. This study aimed to investigate how CYB5R3 overexpression impacts hepatic metabolism in young mice, focusing on mitochondrial biogenesis, lipid metabolism, autophagy and nutrient sensing pathways thus establishing a baseline that allows for subsequent comparisons with older animals. The accrual of CYB5R3 polypeptide exhibited marked sexual...

CONCLUSIONS: Working and non-working older adults showed similar biological circadian rhythms, but working ones had a more robust rest-activity rhythm and higher levels and intensity of physical activity.

A previous study employing fMRI measures of retrieval-related neural selectivity reported that young, but not older, adults employ 'retrieval gating' to attenuate aspects of an episodic memory that are irrelevant to the retrieval goal. We examined whether the weak memories of the older adults in that study rendered goal-irrelevant memories insufficiently intrusive to motivate retrieval gating. Young and older participants studied words superimposed on rural or urban scenes, or on scrambled...

Aging is considered as an independent risk factor for cardiovascular diseases. Common hallmarks of vascular aging include endothelial dysfunction, vascular inflammation, elevated oxidative stress, and telomere dysfunction. Perivascular adipose tissue (PVAT) is the local aggregate of adipose tissue surrounding the vascular bed, serving as a critical regulator of vascular function via either paracrine or endocrine manners. Aging-dependent malfunction of adipose tissues increases the risk of...

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal...