Volume 3 Issue 10, October 2023

Given the unique requirements of older adults, age-friendly product design is becoming increasingly important to promote independence and enhance quality of life. The Global Centre for Modern Ageing calls for a comprehensive, standardized and evidence-based assessment process to incorporate the perspectives of older adults into the design process.

The intestinal epithelium serves as a barrier that facilitates interaction between intrinsic and environmental factors. Aging is accompanied by the gradual deterioration of this barrier. We postulate that barrier dysfunction results from defects in epithelial membrane trafficking that exacerbate age-related metabolic imbalances. Herein, we integrate barrier integrity, protein homeostasis, membrane trafficking and intracellular lipid sensing into an age-determining mechanism.

Human aging is associated with increased rates of many cardiac diseases and tissue remodeling. However, disentangling the mechanisms that underlie normal heart aging from disease processes is challenging. A study now addresses this gap by investigating healthy primate cardiac aging and provides evidence that SIRT2 signaling may regulate cardioprotective effects.

A recent publication in Nature Aging suggests that DOPA decarboxylase may serve as an emerging biomarker that can identify neurodegenerative disorders that are characterized by dopaminergic cell loss. Here we discuss how this finding can assist clinicians and researchers in the differential diagnosis of individuals who present with parkinsonism or cognitive decline.

Senescent cells accumulate with age and promote tissue decline. A broad genomic screen reveals that senescent cells can be eliminated from aged mice by interfering with their unique secretory program. Reducing the capacity of the endoplasmic reticulum by inhibiting the YAP–TEAD complex sensitizes senescent cells to apoptosis.

Microglia exhibit unexpected sex differences in gene expression and accessibility and compromised inflammatory responses during the aging process in mice. We established a mouse model with accelerated microglial turnover (3xDR), which results in aged microglia in non-aged brains. Analysis of this model revealed that aged microglia themselves contribute to cognitive decline.

Parkhitko et al. discuss combinatorial approaches targeting underlying mechanisms of aging across species and describe frameworks to analyze these interactions and their cross-species translational potential.

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.

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.

A single-cell transcriptomic analysis by Lau et al. reveals a homeostatic–chemotactic–phagocytic state transition in microglia upon IL-33 stimulation, identifying VCAM1 as a key regulator of microglial chemotaxis by sensing Aβ plaque-associated ApoE.

Anerillas et al. provide a strategy to eliminate senescent cells that leverages on their secretory needs. Inhibiting YAP–TEAD triggers endoplasmic reticulum stress that eliminates senescent cells from several tissues, improving age-related fibrosis.

Lamin A/C protects alveolar macrophages against nuclear envelope rupture and DNA damage, but it erodes during aging. Lack of lamin A/C leads to senescence and an aging signature, resulting in vulnerability to influenza virus and lung cancer growth.

Ye et al. characterize the cardioprotective effect of SIRT2 in primates and reveal an important role for the SIRT2–STAT3–CDKN2B regulatory axis in primate cardiac aging, improving understanding of the epigenetic mechanism governing cardiac aging.

Li et al. provide a transcriptional and epigenetic characterization of microglia in aging mice brain by developing a three-round depletion–repopulation (3xDR) model to study aged microglia in non-aged brain, giving insights into the molecular mechanism underlying microglia aging.