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This study shows that intermittent fasting (IF) protects against Alzheimer’s disease in a transgenic mouse model. The authors demonstrate that altered metabolism through remodeling of the gut microbiota mediates the beneficial effects of IF regimen.
This study identifies CSF proteins specifically dysregulated along the AD continuum that reflect the multifactorial nature of disease progression. Some of these CSF proteins were used to build biomarker panels with high diagnostic accuracies.
This study found that cerebral small vessel disease was associated with relatively increased glycolysis in the normal-appearing white matter around lesions. Furthermore, lesions tend to develop in white matter that is less glycolytic in healthy humans.
Genetic inactivation of the plant homeodomain 6 gene (Phf6) counteracts transcriptional and epigenetic aging programs in the hematopoietic system and can reverse the decline of hematopoietic stem cell function associated with age.
The prevalence and consequences of vision impairment are increasing due to population growth and aging. This study finds that in India, one in three older adults has distance visual impairment or is blind, which may impact not only how they see the world, but also their overall health and well-being.
Immune system dysfunction has been implicated in the development of dementias, but its causal role remains unknown. Providing converging results from different lines of human research, this study by Lindbohm et al. suggests that autoimmunity may be a modifiable component in diseases causing dementia.
COVID-19 vaccines protect against infection, hospitalization and death in older adults, but their effectiveness is lower in this age group compared to young adults. Here, Palacios-Pedrero et al. show that age-dependent signs of immunosenescence in B and T cells in older adults correlate with poor immunological outcomes after mRNA COVID-19 vaccination but not after natural SARS-CoV-2 infection.
The intestinal microbiome has an important role in health and disease; however, the long-term effects of lifestyle choices on microbiome alterations are incompletely understood. Here, based on extensive lifestyle and medical data collected over 26 years, Si et al. demonstrate that long-term life history can predict current enterotype in older adults.
A metagenomic study of gut, oral and skin microbiota describes a pattern of microbial dysbiosis in more frail institutionalized older adults and identifies the skin as the major reservoir of pathogenicity.
Splicing dysfunction has been observed in Alzheimer’s disease but it remains unclear whether splicing defects have a causal role. Here the authors generate a mouse model with perturbed U1 snRNP activity, recapitulating RNA splicing defects, neuron hyperexcitability, neurodegeneration and synergy with the amyloid cascade when crossed with 5xFAD mice.
Skin thickness and bone density decrease with age; however, the interactions between skin and bone during aging are unclear. Here the authors show that cystatin-A is a skin-derived protein that decreases with age and causes age-related bone loss. Further, topical application of calcipotriol stimulates cystatin-A production in the skin and alleviates bone loss.
One in ten older adults in Canada are victims of elder abuse each year. Older adults with lower physical, mental or cognitive health or history of child maltreatment have elevated risk, while greater social support is protective against this issue.
In this multi-omics study, the authors identified C1q-dependent synapse elimination by both astrocytes and microglia in Alzheimer’s mouse models. While astrocytes preferentially removed excitatory synapses, microglia preferred inhibitory synapses.
RNA splicing has a role in aging and longevity, but the mechanisms involved are incompletely understood. Here the authors show that mRNA splicing components, RNP-6 and RBM-39, act in concert to regulate intron retention, inhibit mTORC1 signaling and prolong life in Caenorhabditis elegans.
Sexual interactions with males shorten the lifespan of the opposite sex in several species, including Caenorhabditis elegans, but the mechanisms are not fully understood. Here the authors use transcriptomic profiling in C.elegans to systematically identify the genetic pathways involved in male-induced demise, which include upregulation of a conserved ion channel that regulates fat metabolism.
With age, muscle stem cells have been reported to undergo a quiescence-to-senescence switch, thus reducing regenerative capacity. Here, using in vitro and mouse models, Guerrero et al. report that treatment with 3-deazaadenosine alleviates senescence and preserves the regenerative potential of muscle and hematopoietic stem cells.
A key challenge for repurposing the licensed drug rapamycin for geroprotection is to avoid side effects from chronic dosing regimens. The authors show in model organisms that a brief administration of the drug early in adulthood has long-lasting beneficial effects that are similar to lifelong treatment.
Goldman et al. demonstrate that meningeal lymphatic vessels play a role in sickness behavior. The authors also find that age-related lymphatic dysfunction increases susceptibility to sickness and that enhancement of meningeal lymphatic function improves movement in sick, aged mice.
The authors introduce a high-throughput machine-learning-based visual frailty index for mice that operates on video data from an open-field assay. The machine-vision-based approach extracts various morphometric and behavioral features from video to model frailty score and age.
Senescent cells are typically identified by a combination of senescence-associated markers, and the phenotype is heterogeneous. Here, using deep neural networks, Heckenbach et al. show that nuclear morphology can be used to predict cellular senescence in images of tissues and cell cultures.