Aging & Longevity

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Substantial shifts in reproductive behaviors have recently taken place in many high-income countries including earlier age at menarche, advanced age at childbearing, rising childlessness and a lower number of children. As reproduction shifts to later ages, genetic factors may become increasingly important. Although monogenic genetic effects are known, the genetics underlying human reproductive traits are complex, with both causal effects and statistical bias often confounded by socioeconomic...

Sex hormone signaling declines during aging, from early midlife through menopause, as a consequence of reduced circulating estrogens and decreased receptiveness to these hormones in target tissues. Estrogens preserve energy homeostasis and promote metabolic health via coordinated and simultaneous effects throughout the brain and body. Age-associated loss of estrogen production during menopause has been implicated in a higher risk for metabolic diseases and increased mortality. However, it...

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People today are choosing to have children later in life, often in their thirties and forties, when their fertility is in decline. We sought to identify and compile effective methods for improving either male or female fertility in this context of advanced reproductive age. We found few clinical studies with strong evidence for therapeutics that mitigate reproductive aging or extend fertility; however, this Perspective summarizes the range of emerging experimental strategies under development....

The female reproductive axis is one of the first organ systems to age, which has consequences for fertility and overall health. Here, we provide a comprehensive overview of the biological process of female reproductive aging across reproductive organs, tissues and cells based on research with widely used physiologic aging mouse models, and describe the mechanisms that underpin these phenotypes. Overall, aging is associated with dysregulation of the hypothalamic-pituitary-ovarian axis,...

Reproductive aging, spanning an age-related functional decline in the female and male reproductive systems, compromises fertility and leads to a range of health complications. In this Perspective, we first introduce a comprehensive framework for biomarkers applicable in clinical settings and discuss the existing repertoire of biomarkers used in practice. These encompass functional, imaging-based and biofluid-based biomarkers, all of which reflect the physiological characteristics of reproductive...

Ovarian aging is characterized by declines in follicular reserve and the emergence of mitochondrial dysfunction, reactive oxygen species production, inflammation, and fibrosis, which eventually results in menopause. Menopause is associated with increased systemic aging and the development of numerous comorbidities; therefore, the attenuation of ovarian aging could also delay systemic aging processes in women. Recent work has established that the anti-diabetic drug Canagliflozin (Cana), a...

Caloric restriction (CR) slows biological aging and prolongs healthy lifespan in model organisms. Findings from the CALERIE randomized, controlled trial of long-term CR in healthy, nonobese humans broadly supports a similar pattern of effects in humans. To expand our understanding of the molecular pathways and biological processes underpinning CR effects in humans, we generated a series of genomic datasets from stored biospecimens collected from n = 218 participants during the trial. These data...

Organellar homeostasis and crosstalks within a cell have emerged as essential regulatory and determining factors for the survival and functions of cells. In response to various stimuli, cells can activate the organellar quality control systems (QCS) to maintain homeostasis. Numerous studies have demonstrated that dysfunction of QCS can lead to various aging-related diseases such as neurodegenerative, pulmonary, cardiometabolic diseases and cancers. However, the interplay between QCS and their...

Exosomes are small extracellular vesicles (EVs), which have the diameter of 50-150 nm and originate from intralumenal vesicles in multivesicular endosomes (MVBs). Exosomes secreted from donor cells are delivered to recipient cells for transferring of exosome cargos, such as proteins, lipids and nucleic acids. The cargo transfer by exosomes has a pivotal role in cell-to-cell communication for many cellular processes; however, the detailed mechanism remains largely elusive. In our recent study, we...

High pressure can create extreme conditions that enable the formation of novel materials and the discovery of new phenomena. However, the ability to preserve the desirable characteristics of materials obtained under high pressure has remained an elusive challenge, as the pressure-induced changes are typically reversible, except for the pressure-induced chemical reactions such as polymerization of hydrocarbons. Here, we propose the concept of "pressure aging" (PA) that enables the permanent...

Many aspects of inflammation increase with aging in mice and humans. Transcriptomic analysis revealed that many murine anti-aging interventions produce lower levels of pro-inflammatory proteins. Here, we explore the hypothesis that different longevity interventions diminish NF-κB levels, potentially mediating some of the anti-inflammatory benefits of lifespan-extending interventions. We found that the NF-κB protein p65 is significantly downregulated in the liver of several kinds of slow-aging...

The global aging population raises concerns about heart failure (HF), yet its association with accelerated biological age (BA) remains inadequately understood. We aimed to examine the longitudinal association between BA acceleration and incident HF risk, assess its modifying effect on genetic susceptibility, and how much BA acceleration mediates the impact of modifiable health behaviors on incident HF. We analyzed 274,608 UK Biobank participants without HF at baseline. Two BA accelerations...

This study aims to investigate the association between metabolomic aging acceleration and body mass index (BMI) phenotypes with mortality and obesity-related morbidities (ORMs). 85,458 participants were included from the UK Biobank. Metabolomic age was determined using 168 metabolites. The Chronological Age-Adjusted Gap was used to define metabolomically younger (MY) or older (MO) status. BMI categories were defined as normal weight, overweight, and obese. Participants were categorized into MY...

INTRODUCTION: During aging, many cellular processes, such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses, become compromised. Urolithin A (UA) and Nicotinamide Riboside (NR) are two naturally occurring compounds known for their anti-inflammatory and mitochondrial protective properties, yet the effects of these natural substances on microglia cells have not been thoroughly investigated. As both UA...

CONCLUSION: There is a correlation between sarcopenia and cognitive function, individuals with sarcopenia performing poorly in overall cognition as well as refined dimensions. The degree of cognition like fluency degenerates over time with increasing severity of sarcopenia.