Volume 3 Issue 9, September 2023

Population aging is a global challenge that poses particular difficulties for low- and middle-income countries (LMICs). So far, there is a dearth of data that describe how aging affects Arab LMICs, which have distinct family structures, caregiving traditions, medical challenges and exposure to climate change. The planned Longitudinal Study of Egyptian Healthy Aging (AL-SEHA) — a member of the cross-nationally comparative family of aging studies around the world — is designed to address these knowledge gaps.

Intestinal barrier dysfunction is a hallmark of aging. Zhang and colleagues examine the replenishment of adherens junctions in the intestine of aged Caenorhabditis elegans and discover the role of the SDPN-1–RAB-10 axis in the dysregulated endocytic recycling, offering new insights into the age-dependent impairment of the intestinal barrier.

Lysosomes are small vesicles in which cellular constituents are enzymatically degraded. Villalobos and colleagues now show that in Caenorhabditis elegans a shift in lysosome morphology from a vesicular to a tubular shape is critical for the lifespan extension triggered by calorie restriction. Moreover, tubular lysosomes form even in well-fed descendants of calorically restricted parents for up to four generations.

By using multimodal MRI in aging humans, we found that noradrenergic brain regions are associated with episodic memory impairment, whereas dopaminergic areas are implicated in working memory impairment. Unravelling the role of changes in these neurotransmitter systems in age-related memory loss contributes to our understanding of the development of neurodegenerative diseases.

Cost-effective and scalable means for detecting amyloid-β positivity in clinical practice are urgently needed. Here, in three memory clinic cohorts, we show that risk stratification with a plasma p-tau217-based model can substantially reduce the need for expensive or invasive testing, while still accurately determining the amyloid-β status of patients with cognitive impairment.

Leveraging a single regression model based on conserved cytosines, we can now measure age in all mammalian tissues. This pan-mammalian epigenetic clock model confirms that aging is conserved across mammalian species at select regions of the DNA, which will accelerate the applicability of research findings from model organisms to humans.

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.

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.

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 report that a change to lysosome morphology, from vesicular to tubular form, supports lifespan extension upon dietary restriction and promotes heightened autophagy and healthy aging when stimulated artificially in well-fed animals.

The intestinal barrier has an important role in organismal homeostasis; however, the mechanisms that mediate intestinal epithelial aging are incompletely understood. Here, Zhang et al. show that RAB-10 functionality is impaired in aging worms, affecting endocytic recycling and, thus, contributing to the age-related deterioration of adherens junctions.

Using multimodal MRI to delineate noradrenergic and dopaminergic nuclei in aging, Dahl et al. found differential associations with episodic and working memory, helping to disentangle the role of the neurotransmitter systems in age-related memory loss.

This study identifies and characterizes evolutionarily conserved cytosine methylation patterns related to age across mammals and establishes pan-mammalian epigenetic clocks.