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Senescence suppresses the integrated stress response and activates a stress-remodeled secretory phenotype

2 months ago
Senescence is a state of indefinite cell-cycle arrest associated with aging, cancer, and age-related diseases. Here, we find that translational deregulation, together with a corresponding maladaptive integrated stress response (ISR), is a hallmark of senescence that desensitizes senescent cells to stress. We present evidence that senescent cells maintain high levels of eIF2α phosphorylation, typical of ISR activation, but translationally repress production of the stress response activating...
Matthew J Payea

Design and methodology of the harmonized diagnostic assessment of dementia for the longitudinal aging study in India: Wave 2

2 months ago
The rising burden of dementia calls for high-quality data on cognitive decline and dementia onset. The second wave of the Harmonized Diagnostic Assessment for the Longitudinal Aging Study in India (LASI-DAD) was designed to provide longitudinal assessments of cognition and dementia in India. All Wave 1 participants were recruited for a follow-up interview, and a refresher sample was drawn from the Longitudinal Aging Study in India, a nationally representative cohort of Indians aged 45 and older....
Pranali Y Khobragade

Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death

2 months ago
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if...
Ignacio Benedicto

Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan

2 months ago
The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries and gametes across the reproductive lifespan. Ovaries exhibit localized structural and cell-type-specific enrichment of stable macromolecules in both the follicular and extrafollicular environments. Moreover, ovaries and...
Ewa K Bomba-Warczak

Neurocognitive correlates of cerebral mitochondrial function and energy metabolism using phosphorus magnetic resonance spectroscopy in older adults

2 months ago
The goal of the current study was to learn about the role of cerebral mitochondrial function on cognition. Based on established cognitive neuroscience, clinical neuropsychology, and cognitive aging literature, we hypothesized mitochondrial function within a focal brain region would map onto cognitive behaviors linked to that brain region. To test this hypothesis, we used phosphorous (^(31)P) magnetic resonance spectroscopy (MRS) to derive indirect markers of mitochondrial function and energy...
Francesca V Lopez

Plasma proteomics-based organ-specific aging for all-cause mortality and cause-specific mortality: a prospective cohort study

2 months ago
Individual's aging rates vary across organs. However, there are few methods for assessing aging at organ levels and whether they contribute differently to mortalities remains unknown. We analyzed data from 45,821 adults in the UK Biobank, using plasma proteomics and machine learning to estimate biological ages for 12 major organs. The differences between biological age and chronological age, referred to as "age gaps," were calculated for each organ. Partial correlation analyses were used to...
Renjia Zhao

Clonal dynamics after allogeneic haematopoietic cell transplantation

2 months ago
Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those from a donor^(1,2). Here, to quantify dynamics of long-term stem cell engraftment, we sequenced genomes from 2,824 single-cell-derived haematopoietic colonies of ten donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT³. With younger donors (18-47 years at transplant), 5,000-30,000 stem cells had engrafted and were still contributing to haematopoiesis at the...
Michael Spencer Chapman

The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis

2 months ago
Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N-acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti-aging effects of cysteine, we systematically reviewed and...
Yue Ma

Arginine metabolism is a biomarker of red blood cell and human aging

2 months ago
Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics...
Julie A Reisz