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Partial reprogramming to enhance regeneration and mitigate age-related phenotypes is limited by toxicity. Parras et al. report a transgenic reprogrammable mouse strain with attenuated toxicity, by avoiding OSKM expression in the liver and intestine.
There is scant evidence for how intrinsic capacity (IC), the combination of an individual’s physical and mental capacities, varies throughout adulthood. In this study, the authors demonstrated a method to establish IC reference centile curves using data of individuals aged 20–102 years from the French INSPIRE-T cohort.
Unlike animals, plants prevent pathological polyQ aggregation through chloroplast proteostasis. Expression of the chloroplast protein SSP in human cell and nematode models prevents disease-related protein aggregation and neurodegeneration.
Ferrari-Souza et al. show that the APOEε4 allele potentiates the deleterious effects of Aβ on the longitudinal accumulation of tau tangles in neocortical brain regions, via tau phosphorylation, which coincides with brain atrophy and clinical decline.
Pereira, Kumar et al. identify cerebrospinal fluid DOPA decarboxylase as a promising biomarker for Parkinsonian disorders that may be used for early preclinical detection of Parkinsonian disorders as well as determining the risk of conversion to Lewy body disease.
Urolithin A (UA) is a gut microbiome-derived metabolite that has been therapeutically explored in aging-related diseases and exerts its benefits in part through effects on mitochondria. Here Girotra, Chiang and colleagues show that UA administration boosts mitochondrial recycling in hematopoietic stem cells and reverses aging features in both the hematopoietic and immune systems.
Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.
The authors found that klotho, a longevity and cognition-enhancing factor, can increase the levels of multiple platelet factors in plasma, including PF4. PF4 treatment, which permeated the brain, in turn, enhanced cognition in young and old mice.
De-Souza, Thompson and Taylor demonstrate that pathogen-associated odorants can activate the UPR cell non-autonomously in C. elegans via neuronal TGF-β signaling, leading to extended lifespan and enhanced clearance of toxic proteins.
A mass spectrometric analysis of plasma tau species identifies phosphorylated tau peptides p-tau217, p-tau231 and p-tau205 with distinct correlations with amyloid and tau pathologies and emergences along the AD continuum.
Cerebrospinal fluid (CSF) tests are used in the clinical diagnosis of Alzheimer’s disease. This study found that CSF tau phosphorylation at two sites (T217 and T205) is a better test for Alzheimer’s disease pathology than currently available tests.
Using chronic in vivo imaging of the mouse hippocampus over months, this study reveals aging-associated alterations of neural stem cells and their neuronal progeny that lead to reduced clonal output of individual neural stem cells with advancing age.
Using samples and data from the CALERIE study, a human randomized controlled trial of long-term caloric restriction, the authors find that the intervention slows DunedinPACE, a DNA methylation measure of the pace of aging.
Frailty of the aged brain may relate to impaired vascular control and limitations in energy supply. The authors report an age-related decrease in responsivity of brain microvessels, accompanied by a decrease in vessel density and loss of vascular mural cell processes.
Dietary supplementation of the clinical PI3K inhibitor alpelisib (Piqray) extends the lifespan of male and female mice and is associated with greater strength and balance but reduced bone mass and mild hyperglycaemia.