Aging & Longevity

Alzheimer's disease (AD), characterized by progressive cognitive decline, represents a major public health challenge in aging societies. Since the proposal of the amyloid cascade hypothesis, Aβ-targeted therapeutic strategies have dominated this field for over three decades. Although recent anti-Aβ antibodies have shown modest promise, their limited clinical benefits coupled with safety concerns underscore the necessity of re-evaluating the pathological mechanisms underlying AD. Cerebral...

Muscle regenerative capacity declines with aging and disease, which leads to muscle loss and reduced lifespan. Muscle regenerative failure is related to a disrupted network orchestrated by multiple muscle-harbored cell types; whether and how the interplay between macrophages and myofibers contributes to this process is largely unknown. Herein, we report upregulation of histone methyltransferase G9a in both aged human muscle and mouse muscle after injury. Deletion of G9a in either myeloid cells...

Cancer-related lymphedema (CRL) is an incurable disease characterized by progressive swelling of extremities. One of the risk factors in developing CRL is cancer treatments, including surgery and radiation. This leads to damage to the lymphatic system, causing accumulation of interstitial fluid, infiltration of inflammatory cells and cytokine release, tissue remodeling, accumulation of subcutaneous fat, and fibrosis. Radiation therapy (RT) inhibits lymphatic proliferation and survival by...

Identifying biomarkers that identify vulnerability to age-related cognitive decline is a major priority in aging research. Adropin, a circulating peptide that regulates metabolic and vascular homeostasis, has been associated with cognitive performance in humans, but its relevance across species has remained unclear. Here we report low plasma adropin concentrations associate with poor decision-making in aged rhesus macaques subject to an increasing food choice test paradigm. Animals with higher...

Nanoparticle sintering is typically regarded as a deactivation mechanism for supported metal catalysts, motivating efforts to maximize metal dispersion. Here we demonstrate the opposite trend for platinum catalysts in light-alkane oxidation. Intentionally pre-sintered platinum particles, tens of nanometers in size and supported on thermally stable magnesium aluminate, show higher activity than highly dispersed platinum species for propane oxidation. Theory-guided adsorption calculations suggest...

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The cerebellum contains most of the brain's neurons and supports many functions, yet how it changes with age remains unclear. Here we used three brain imaging studies spanning 47,000 adults and examined how different parts of the cerebellum age and their relation to cognition. We characterized cerebellar aging using volumetry and the T1-weighted/T2-weighted ratio, and corroborated these findings with quantitative magnetic resonance imaging in an independent sample. We show a spatially...

Sirtuins are deacetylases implicated in stress responses and longevity in mammals^(1,2). Although their differential impact on disease for the two sexes has been noted^(3-7), the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7^(-/-) female mice have decreased fitness throughout their lifespan. Notably, SIRT7 preferentially localizes to the sex chromosomes. In female individuals, SIRT7 loss affects...

Anode-less aqueous zinc batteries offer a promising route to energy-dense and intrinsically safe energy storage, yet their practical deployment is hindered by poor reversibility under constrained zinc inventory. Here, we identify galvanic corrosion between deposited zinc and current collectors as a critical but previously underappreciated degradation pathway in anode-less aqueous zinc batteries. A hybrid passivation layer, comprising an electrically insulating polymer matrix embedded with...

Cognitive decline is a central feature of aging and a major determinant of disability and mortality. Understanding cognitive trajectories is essential for identifying individuals at risk and informing preventive strategies. In this study, we estimated transition probabilities across cognitive states and examined predictors of cognitive deficit and mortality among 1,413 community-dwelling older adults for nine years. Cognitive status was assessed at baseline and at two follow-up waves (2006,...

Metabolic disorders, particularly insulin resistance, are increasingly recognized as accelerators of female reproductive decline. However, the molecular mechanisms by which peripheral metabolic stress translates into impaired ovarian reserve remain incompletely understood. Here, we propose that protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling, serves as a molecular bridge linking systemic insulin resistance to aging-relevant ovarian dysfunction and can be...

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) deposition, tau hyperphosphorylation, and chronic neuroinflammation. Emerging evidence from preclinical models suggests that aberrant immune crosstalk between regulatory T cells (Tregs) and microglia may contribute to disease progression, though its precise role in human AD remains to be fully elucidated. In rodent models, Tregs have been shown to cross the blood-brain barrier and, through cell-contact-dependent mechanisms and...

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Preservation of host fitness is a common feature of longevity and immunity to infection. In this issue of Immunity, Triana-Martinez et al. reveal that p16^(High) senescence-associated immune cells promote disease tolerance and healthy aging. Mechanistically, this is dependent on Toll-like receptor 7 (TLR7) and stimulator of interferon genes (STING) innate immune signaling controlling adenosine concentrations.

All immune cells engage in cholesterol metabolism, which generates a spectrum of bioactive metabolites that mainly include cholesterol itself, its biosynthetic intermediates, and oxidized or sulfated derivatives. These metabolites regulate not only cellular metabolism but also immune signaling. In addition, several functional proteins within cholesterol metabolic pathways exert non-canonical signaling functions that shape immune cell responses. Distinct immune cell types adopt specialized...

The perivascular glymphatic system promotes cerebrospinal fluid-interstitial fluid (CSF-ISF) interaction and macromolecular waste clearance and is an important determinant of brain homeostasis, the performance of which deteriorates with age. Astrocyte biology, vascular integrity, and age-associated cerebrovascular dynamic alterations interfere with the polarization of aquaporin-4 (AQP4) water channels on astrocytic endfeet, decreasing the clearance of aggregation-prone proteins, such as...

Brain aging is associated mainly with a decline in cognitive function and is a major risk factor for various neurodegenerative disorders (NDDs). Major hallmarks of aging include oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and impaired proteostasis. Although caloric restriction (CR) has consistently demonstrated neuroprotective effects, its long-term effects in humans remain challenging. Consequently, CRMs such as metformin, spermidine, and curcumin have been widely...

Cancer is increasingly relevant to ageing societies, yet progress in cancer control is difficult to assess when population years of life lost (YLL) to cancer appear stable. Using Danish registers, we followed 4.26 million residents aged ≥50 years (1980-2019) and estimated YLL under observed and counterfactual scenarios, separating demography and incidence from post-diagnosis outcomes. From the 1980s to the 2010s, YLL per individual changed little (men 2.3 to 2.1; women 2.5 to 2.2), while YLL per...