Aging & Longevity

Senolytic CAR-T cells targeting uPAR induce dose-dependent toxicities. Although dosage adjustment mitigates these toxicities in laboratory mice, clinical translation remains challenging owing to the unpredictability of CAR-T cell proliferation across heterogeneous patient populations. In contrast, bispecific T-cell engagers (BiTEs) offer a safer alternative with superior dose-titratability. Here, we have developed a GFD-CD3 BiTE by employing the growth factor-like domain (GFD) of the natural...

Maintenance of lipid and redox homeostasis is essential for stress resistance and longevity, but the transcriptional networks coordinating these processes remain incompletely understood. In Caenorhabditis elegans, the transcription factors SKN-1A/Nrf1 and SKN-1C/Nrf2 mediate distinct stress responses that promote proteostasis, lipid homeostasis, and oxidative stress resistance. Here, we identify the Krüppel-like factor KLF-1 as a regulator of lipid accumulation that modulates SKN-1 activity....

Cognitive impairment (CI) associated with aging and immunosenescence is linked to metabolic alterations. Microglial senescence and dysregulated autophagy have been implicated as major contributors to this process, but the underlying metabolic regulators remain unclear. This study aimed to identify key metabolic regulators of CI and elucidate their underlying mechanisms. Human cohort analyses, older and D-galactose (D-gal)-induced mouse models, and microglial cell models were integrated to...

Interactions between nervous system and adipose tissue are involved in the regulation of adipocyte browning. However, whether microglial activation participates in the regulation of cold exposure-induced sympathetic innervation and adipocyte browning is unclear. Here, we demonstrate that RNA m6A demethylase ALKBH5 in the microglia nucleus of hypothalamus (PVH) region inhibits cold exposure-induced adipocyte browning in the subcutaneous white adipose tissue (sWAT) of male mice. The single...

As delayed childbearing becomes increasingly common, elucidating the mechanisms of age-related placental senescence is critical for the development of effective therapeutic strategies. Here, we integrate metabolomics, single-cell RNA sequencing, and spatial transcriptomics to uncover conserved features of aged placentas in humans, mice, and pigs, namely, increased macrophage CD38 expression and NAD⁺ deficiency. Through pharmacological and genetic approaches, we demonstrate that macrophage CD38...

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Aging is an inevitable and progressive physiological process marked by a decline in cellular function, accumulation of somatic mutations, decreased ability to maintain homeostasis, and increased tissue and organ dysfunction. These changes contribute to the onset and progression of various age-related diseases. Accumulation of reactive oxygen species (ROS) has been identified as a key mediator of the aging process. Mitochondria, the primary producers of ROS, accumulate defects with aging, leading...

Mineralized blood vessels (MBV) are a form of vascular pathology associated with cerebrovascular aging and neurodegeneration; however, their regional distribution and clinicopathological correlates in Alzheimer disease (AD) remain poorly characterized. We examined 265 decedents with intermediate/high AD neuropathologic change from three Alzheimer's Disease Research Centers (Columbia University, University of California San Diego, and University of California Davis). Hematoxylin and eosin-stained...

Antiretroviral therapy (ART) has significantly increased life expectancy of people living with HIV (PLWH). Nonetheless, despite effective virological control, PLWH are faced with accelerated aging, characterized by higher prevalence of age-related comorbidities than the general population. Persistent inflammation and activation of innate immunity seem to drive this immunosenescent phenotype. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is increasingly...

Neuronal loss is a hallmark of neurodegenerative diseases. Phosphatidylserine (PS), a key "eat me" signal, is exposed on stressed viable neurons, triggering their premature phagocytosis by activated glia. We investigated whether PS masking could serve as a universal strategy to prevent neuronal loss in two distinct Drosophila models of neurodegeneration: an adult-stage-specific knockdown of skpA and a Huntington's disease model initiated during embryogenesis. Both models exhibit neuronal loss,...

The functional decline of the hematopoietic system during aging affects organismal function and contributes to reduced healthspan. Quantifying hematopoietic aging holds great scientific and clinical relevance. Alterations in chromatin architecture are a well-established hallmark of aging that encode rich and informative signatures of the aging process, yet they remain largely unexplored as quantitative markers. Here, we present an interpretable deep learning approach based on convolutional...

Autophagy is widely proposed to decline with age; however, direct evidence across human cell types remains limited. Moreover, it is unclear whether age-associated changes in autophagy-gene transcription are accompanied by corresponding changes in autophagic activity, and whether autophagic activity relates to physiological function during aging. We performed transcriptomic and functional autophagy analyses across subject-matched human cell types from a healthy aging cohort. Autophagy-related...

Nematode growth medium (NGM) has been the standard culture medium for Caenorhabditis elegans (C. elegans) for over five decades and contains peptone to support proliferation of the bacterial food source, Escherichia coli OP50. However, the increasing use of paraformaldehyde (PFA)-killed OP50 in studies of metabolism, aging, and host-microbe interactions raise the question of whether peptone remains necessary once bacterial proliferation has been eliminated. Here, we systematically compared...

This study examined the impact of nine years of continued cycling exercise on physiological function in older exercisers, viewed as a model of inherent biological aging free from the negative effects of inactivity. A range of cardiorespiratory indices were measured, with peak oxygen consumption (V̇O(2peak)) as the primary outcome. Of an original 125 cyclists first assessed in 2012-2013, 82 (53 males, 29 females) returned 9 years later (aged 64-86 years at follow up). V̇O(2peak) declined by 19.7%...

Eccentric exercise is widely used in rehabilitation protocols for older adults. However, the age-related behavior of the muscle-tendon unit (MTU) during eccentric actions remains incompletely understood, especially regarding muscle-tendon decoupling and its influence on fascicle dynamics and force production. Better characterizing these mechanisms would help optimize the design of rehabilitation protocols in older individuals. This study aimed to investigate age-related differences, while...

DNA storage is a promising solution to data explosion due to its high density and longevity. However, existing coding methods struggle to efficiently avoid error-prone sequences while retaining usable ones, leading to low density and high copy numbers. Here we show Siyuan Code, a DNA storage codec that achieves theoretically optimal density. Our method maps binary data to nearly all suitable low-error sequences in a one-to-one manner, using our data structure to catalog and avoid error-prone...

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CONCLUSION: Evidence on cognitive ageing among older Latin American immigrants remains limited and geographically concentrated. Greater research diversity and more precise characterisation of immigrant populations are needed to better understand cognitive ageing and to inform equitable, culturally responsive policies and interventions.

Despite comprising nearly one in 10 people living with HIV (PLHIV) in Brazil, older adults aged 60 years and above remain profoundly underrepresented in psychosocial research. This multicenter study is the first age-restricted (≥ 60 years) subgroup analysis of the Brazilian PLHIV Stigma Index 2.0. The present secondary analysis yielded a sample of 138 older adults (M age = 64.3 years, SD = 4.1; 52.9% male; 57.2% Black or Brown). Path analysis with 5000-resample bootstrapping and full-information...