Aging & Longevity

Model organisms such as yeast, worms, flies, and mice were key to discovering genes and other factors controlling life span and directly improved our understanding of human aging. Today, genomic tools allow study of a broader range of species, including those with short or long life spans, closely related species with different aging rates, or differences in interspecies aging. Models such as killifish, bats, and ants have much to teach us about human aging. They also reveal a flexible...

Mitochondria are no longer viewed solely as ATP- or metabolite-generating organelles but as key regulators of cellular signaling that shape physiologic aging. Contrary to earlier theories linking aging to mitochondrial DNA mutations and oxidative damage, current evidence shows that these factors do not causally limit physiologic aging. Instead, an evolving literature links age-related loss of mitochondrial signaling and function to important physiologic changes of aging. Moreover, mild...

Caenorhabditis elegans has been at the forefront of research on mechanisms of age-related decline for the past 30 years. Despite its popularity in longevity research, C. elegans is underappreciated for its potential to study complex behaviors and the progressive decline in these functions with age. Using assays of learning and memory, we have identified genetic pathways that regulate these behaviors and identified new mechanisms to boost these functions with age in both worms and mice. Because...

Aging is the greatest risk factor for most diseases. We propose that aging manifests as disease as a function of tumor-suppressive capabilities. Adequate tumor suppression results in cell death or an accumulation of damaged cells leading to inflammation and tissue dysfunction that underlies diseases such as cardiovascular disease, neurodegenerative diseases, or type 2 diabetes. Conversely, inadequate tumor suppression leads to cancer. Telomeres are central to this process because they oppose...

The past 40 years have witnessed significant progress in aging research. Although aging was once considered a stochastic process, it is now understood to be regulated by pathways and processes that can be dissected with modern cellular and molecular biology approaches. The aberrant accumulation of cells undergoing cellular senescence and an increase in chronic, sterile inflammation are two of those aging hallmarks. Here we discuss how these processes are connected and how the relationship...

The unstable electrolyte-electrode interface and the trace H(2)O in commercial organic electrolytes critically limit the cycling life of batteries. Herein, a locking-chain sodium 4,4'-(1,4-phenylenebis(oxy))-bis(butane-1-sulfonate)-15-crown-5 (15PBS) is designed for phase-to-interface electrolyte optimization. In the electrolyte phase, the strong hydrophilic sulfonate groups and 15-crown-5 in 15PBS effectively transform H(2)O from a reactive aggregated state (strong H-bond) into an inactive...

African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate that can be bred in captivity, making it an ideal model organism for aging studies. However, whether the animal can be used for studying cardiac aging and whether cellular senescence contribute to this ageing process remain unclear. Here, we conducted a longitudinal study on the GRZ strain, aiming to identify phenotypic and functional markers for cardiac aging. We found that cardiac ageing in GRZ fish can be...

There is robust evidence that senescence can be propagated in vitro through mechanisms including the senescence-associated secretory phenotype, resulting in the non-cell-autonomous induction of secondary senescence. However, the induction, regulation and physiological role of secondary senescence in vivo remain largely unclear. Here we generated senescence-inducible mouse models expressing either the constitutively active form of MEK1 or MKK6 and mCherry, to map primary and secondary senescent...

Regular physical activity (PA) and reduced sedentary behavior (SB) are well-established factors in promoting health and lowering the risk of chronic diseases. However, their relationship with unplanned hospitalizations remains unclear. Our aim was to investigate the associations between PA and SB parameters and the risk of unplanned hospital admissions, and the length of hospital stays in older adults. We analyzed data from 657 older adults aged ≥ 66 years from the Swedish SNAC-K study...

Identifying aging-associated biomarkers applicable for multiple tissues is challenging but crucial for assessing tissue aging. Here, we obtained and analyzed 456 transcriptomes on 17 organs from 30 C57BL/6 J mice with different ages, revealing the consistently upregulated mRNAs of Ighm, C4b, and Ccl8 in most aged organs. This finding received support from independent transcriptomic and proteomic datasets and was further validated through western blot, enzyme-linked immunosorbent assay (ELISA),...

Cognitive decline during aging represents a major societal burden, causing both personal and economic hardship in an increasingly aging population. Many studies have found that the proteostasis network, which functions to keep proteins properly folded, is impaired with age, suggesting that there may be many proteins that incur structural alterations with age. Here, we used limited proteolysis mass spectrometry, a structural proteomic method, to globally interrogate protein conformational changes...

Chemotherapy-induced different cell fates play crucial roles in cancer treatment outcomes; however, the cross-talk between the cell fates during cancer recurrence remains unclear. Here, we found that the transition from cellular senescence to pyroptosis promoted small cell lung cancer (SCLC) recurrence after cisplatin and etoposide treatment. Parts of the senescent SCLC cells induced by chemotherapy showed positive cytoplasmic chromatin fragments (CCFs), and CCFs activated the ubiquitin-editing...

Gut microbiota delays aging by regulating the immune, metabolic, and neurological functions of the host. However, current research on novel probiotics with antiaging properties significantly lags, impacting their application in clinical treatments. In this study, metagenomics, culturomics, and probiotic property screening were used to identify Bifidobacterium pseudocatenulatum NCU-08 as a potential probiotic with anti-aging properties. In addition, B. pseudocatenulatum NCU-08 effectively...

As the brain ages, it undergoes a series of molecular and cellular changes that affect its structure and function, contributing to age-related disorders-particularly cerebrovascular diseases and diminished regenerative capacity following ischemic injury. Despite significant research efforts, effective therapies for brain rewiring and functional recovery after cerebral ischemia remain elusive. A deeper understanding of the cellular and molecular mechanisms involved in the post-acute phase of...

Aging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss is a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly investigated. Here, we analyzed tissue-unique methylation patterns in healthy and diseased human organs, revealing that for several diseases these patterns degrade, regressing to a mean form. We interpret this as epigenetic...

BACKGROUND: Aging of the brain is associated with cognitive decline and recognized as a major risk factor for the development of neurodegenerative diseases. On a cellular level, brain aging is accompanied by a progressive increase of the basal pro-inflammatory tonus, leading to the activation of phagocytic pathways in brain-resident microglia and disruptive effects on synaptic neurotransmission. While the aging process affects all brain compartments at different velocities and one of the...

Cardiorespiratory fitness (CRF), measured by VO(2)max, is an indicator of vascular functioning that can influence the integrity of brain microstructural white matter tracts in aging. How CRF is related to regional patterns of white matter bundles for magnetic resonance imaging (MRI) diffusion metrics (axial diffusivity, AD; radial diffusivity, RD; mean diffusivity, MD; fractional anisotropy, FA) has been less studied. We used a multivariate analysis method, the Scaled Subprofile Model (SSM), to...

INTRODUCTION: Age-related decline in visual processing has been observed in association with reduced orientation selectivity and decreased signal-to-noise ratios in the primary visual cortex (V1). Elevated noise correlations between neurons are associated with impaired visual discrimination in aging; however, less is known about therapeutic interventions that could preserve visual cortical function during aging. In this study, we investigated the effects of metformin treatment on age-related...

Aging is a multifactorial process driven by accumulating cellular damage. Ferroptosis-an iron-dependent, lipid peroxidation-mediated form of cell death-has emerged as a critical contributor to age-related tissue degeneration. This review synthesizes current evidence linking ferroptosis to key aging hallmarks, including oxidative stress, chronic inflammation, mitochondrial dysfunction, and dysregulated iron metabolism. Central to these interactions is the age-associated decline in antioxidant...

CONCLUSIONS AND IMPLICATIONS: Caregivers' decisions to retire from the labor force were mostly driven by their care recipients' care needs. These findings may suggest the need for flexible workplace policies that accommodate varied caregiving responsibilities to support caregivers. Increasing access to congregate residential and respite care may be another strategy that could reduce caregiver burden and retirement from the labor force.