Aging & Longevity

The mammalian nervous system is impacted by aging. Aging alters brain architecture, is associated with molecular damage, and can manifest with cognitive and motor deficits that diminish the quality of life. Astrocytes are glial cells of the CNS that regulate the development, function, and repair of neural circuits during development and adulthood; however, their functions in aging are less understood. Astrocytes change their transcriptome during aging, with astrocytes in areas such as the...

The contemporary understanding that the immune response significantly supports higher brain functions has emphasized the notion that the brain's condition is linked in a complex manner to the state of the immune system. It is therefore not surprising that immunity is a key factor in shaping brain aging. In this perspective article, we propose amending the Latin phrase "mens sana in corpore sano" ("a healthy mind in a healthy body") to "a healthy mind in a healthy immune system." Briefly, we...

The cognitive neuroscience of human aging seeks to identify neural mechanisms behind the commonalities and individual differences in age-related behavioral changes. This goal has been pursued predominantly through structural or "task-free" resting-state functional neuroimaging. The former has elucidated the material foundations of behavioral decline, and the latter has provided key insight into how functional brain networks change with age. Crucially, however, neither is able to capture brain...

Every cell in the body has a biological sex. The expansion of aging research to investigate female- and male-specific biology heralds a major advance for human health. Unraveling and harnessing mechanistic etiologies of sex differences may reveal new diagnostics and therapeutics for the aging brain.

As global life expectancy increases, age-related brain diseases such as stroke and dementia have become leading causes of death and disability. The aging of the neurovasculature is a critical determinant of brain aging and disease risk. Neurovascular cells are particularly vulnerable to aging, which induces significant structural and functional changes in arterial, venous, and lymphatic vessels. Consequently, neurovascular aging impairs oxygen and glucose delivery to active brain regions,...

DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage. Chromosome conformation capture-based approaches have shown that,...

Brain aging leads to a decline in cognitive function and a concomitant increase in the susceptibility to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A key question is how changes within individual cells of the brain give rise to age-related dysfunction. Developments in single-cell "omics" technologies, such as single-cell transcriptomics, have facilitated high-dimensional profiling of individual cells. These technologies have led to new and comprehensive...

As the brain transitions from wakefulness to sleep, processing of external information diminishes while restorative processes, such as glymphatic removal of waste products, are activated. Yet, it is not known what drives brain clearance during sleep. We here employed an array of technologies and identified tightly synchronized oscillations in norepinephrine, cerebral blood volume, and cerebrospinal fluid (CSF) as the strongest predictors of glymphatic clearance during NREM sleep. Optogenetic...

Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP). The...

Volcano deformation can be detected over timescales from seconds to decades, offering valuable insights for magma dynamics. However, these signals are shaped by the long-term evolution of magmatic systems, a coupling that remains poorly understood. Here we integrate thermal models of crustal-scale magmatism with thermo-mechanical simulations of ground deformation. This allows us to determine the influence of magmatic flux over 10⁵-10⁶ years on viscoelastic deformation spanning a 10-year...

Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant...

It remains unclear whether the benefits of adhering to a healthy lifestyle outweigh the effects of high genetic risk on cognitive decline. We examined the association of combined lifestyle factors and genetic risk with changes in cognitive function and six specific dimensions of cognition among older adults from the Chinese Longitudinal Healthy Longevity Survey (1998-2018, n = 18,811, a subset of 6301 participants with genetic information). Compared to participants with an unfavorable lifestyle,...

Traditionally, differences among individuals have been divided into genetic and environmental causes. However, both types of variation can underlie regulatory changes in gene expression - that is, epigenetic changes - that persist across cell divisions (developmental differentiation) and even across generations (transgenerational inheritance). Increasingly, epigenetic variation among individuals is recognized as an important factor in human diseases and ageing. Moreover, non-genetic inheritance...

CONCLUSION: Cognitive impairment in elderly individuals in Chengdu is serious. We can intervene in and improve cognitive impairment in elderly people by controlling blood pressure and blood sugar, treating depressive and anxiety symptoms and developing community colleges for elderly people and increasing satisfaction with life.

CONCLUSIONS: Our findings indicate that poor sleep quality is related to various manifestations of long COVID in older populations. A comprehensive assessment and multidisciplinary management of sleep health and long COVID may be essential to ensure healthy aging in the future.

Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.4 years at Year 1, 51% women, and 33% Black) from the Health, Aging and Body Composition (Health ABC) study....

This study aimed to document the typology of social participation and network among older Canadians and examine their associations with health. Using 2011-2015 cross-sectional data from the Canadian Longitudinal Study on Aging, a latent profile analysis was conducted to identify patterns of social participation and network, and multinomial logistic regressions examined associations with self-rated health. Four types of social participation and networks characterized older Canadians: diverse...

Integrating dietary interventions have been extensively studied for their health benefits, such as Alzheimer's disease, Huntington's disease, and aging. However, it is necessary to fully understand the mechanisms of long-term effects and practical applications of these dietary interventions for health. A 10-week intermittent fasting (IMF) regimen was implemented on the aging animals in the current study. The variations of cerebral functions were analyzed employing a comprehensive experimental...

Epigenetic clocks are a common group of tools used to measure biological aging-the progressive deterioration of cells, tissues, and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues, but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related...

CONCLUSIONS: Patients' perspectives may enable or hinder deprescribing, emphasizing the importance of soliciting these perspectives during shared decision-making. Effective deprescribing will benefit from understanding patients' perspectives and fostering patient-provider communication about medication changes throughout the disease course.