Aging & Longevity

Bioengineered human colon organoids with in vivo-like cellular complexity and function

1 month 1 week ago
Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called "mini-colons."...
Olga Mitrofanova

Maternal care leads to the evolution of long, slow lives

1 month 1 week ago
Animals, and mammals in particular, vary widely in their "pace of life," with some species living long lives and reproducing infrequently (slow life histories) and others living short lives and reproducing often (fast life histories). These species also vary in the importance of maternal care in offspring fitness: In some species, offspring are fully independent of their mothers following a brief period of nutritional input, while others display a long period of continued dependence on mothers...
Matthew N Zipple

TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice

1 month 1 week ago
Moderate physical training has been shown to hinder age-related memory decline. While the benefits of physical training on hippocampal memory function are well-documented, little is known about its impact on working memory, which is linked to the prelimbic cortex (PrL), one major subdivision of the prefrontal cortex. Here, we examined the effects of physical training on spatial working memory in a well-established animal model of physical training, starting at 16 months of age and continuing for...
Yun He

HDAC4 influences the DNA damage response and counteracts senescence by assembling with HDAC1/HDAC2 to control H2BK120 acetylation and homology-directed repair

1 month 1 week ago
Access to DNA is the first level of control in regulating gene transcription, a control that is also critical for maintaining DNA integrity. Cellular senescence is characterized by profound transcriptional rearrangements and accumulation of DNA lesions. Here, we discovered an epigenetic complex between HDAC4 and HDAC1/HDAC2 that is involved in the erase of H2BK120 acetylation. The HDAC4/HDAC1/HDAC2 complex modulates the efficiency of DNA repair by homologous recombination, through dynamic...
Eros Di Giorgio

Unifying considerations and evidence of macrophage activation mosaicism through human CSF1R and M1/M2 genes

1 month 1 week ago
Addressing the mononuclear phagocyte system (MPS) and macrophage M1/M2 activation is important in diagnosing hematological disorders and inflammatory pathologies and designing therapeutic tools. CSF1R is a reliable marker to identify all circulating MPS cells and tissue macrophages in humans using a single surface protein. CSF1R permits the quantification and isolation of monocyte and dendritic cell (DC) subsets in conjunction with CD14, CD16, and CD1c and is stable across the lifespan and sexes...
Federica Orsenigo

Brain age has limited utility as a biomarker for capturing fluid cognition in older individuals

1 month 1 week ago
One well-known biomarker candidate that supposedly helps capture fluid cognition is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI. To formally evaluate the utility of Brain Age for capturing fluid cognition, we built 26 age-prediction models for Brain Age based on different combinations of MRI modalities, using the Human Connectome Project in Aging (n=504, 36-100 years old). First, based on commonality analyses, we found a...
Alina Tetereva

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life

1 month 1 week ago
Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be...
Joseph Adkins-Jablonsky

Three-dimensional chromatin reorganization regulates B cell development during ageing

1 month 1 week ago
The contribution of three-dimensional genome organization to physiological ageing is not well known. Here we show that large-scale chromatin reorganization distinguishes young and old bone marrow progenitor (pro-) B cells. These changes result in increased interactions at the compartment level and reduced interactions within topologically associated domains (TADs). The gene encoding Ebf1, a key B cell regulator, switches from compartment A to B with age. Genetically reducing Ebf1 recapitulates...
Fei Ma

DNA mismatch and damage patterns revealed by single-molecule sequencing

1 month 1 week ago
Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases^(1,2). Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired^(3,4). However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity...
Mei Hong Liu

Conserved epigenetic hallmarks of T cell aging during immunity and malignancy

1 month 1 week ago
Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such 'epigenetic clocks' appear conserved among mammals, but whether they are cell autonomous and restricted by maximal organismal lifespan remains unknown. We used a multilifetime murine model of repeat vaccination and memory T cell transplantation to test whether epigenetic aging tracks with cellular replication and if such clocks continue 'counting' beyond species lifespan. Here we...
Tian Mi

Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration

1 month 1 week ago
The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-Cre^(ERt2)...
Zhijia Tan

Sex-dependent regulation of vertebrate somatic growth and aging by germ cells

1 month 1 week ago
The function of germ cells in somatic growth and aging has been demonstrated in invertebrate models but remains unclear in vertebrates. We demonstrated sex-dependent somatic regulation by germ cells in the short-lived vertebrate model Nothobranchius furzeri. In females, germ cell removal shortened life span, decreased estrogen, and increased insulin-like growth factor 1 (IGF-1) signaling. In contrast, germ cell removal in males improved their health with increased vitamin D signaling. Body size...
Kota Abe

Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice

1 month 1 week ago
The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus...
Yan Wang

Regulation of cell function and identity by cellular senescence

1 month 1 week ago
During aging and in some contexts, like embryonic development, wound healing, and diseases such as cancer, senescent cells accumulate and play a key role in different pathophysiological functions. A long-held belief was that cellular senescence decreased normal cell functions, given the loss of proliferation of senescent cells. This view radically changed following the discovery of the senescence-associated secretory phenotype (SASP), factors released by senescent cells into their...
Anda Huna

Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight

1 month 1 week ago
Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative...
JangKeun Kim

Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain

1 month 1 week ago
Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The...
Jacob W Vogel
2 hours 4 minutes ago
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