Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
From the blood immunome of 1,001 individuals aged 8–96 years, the authors used deep learning to develop an inflammatory clock of aging (iAge) that tracks with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The main contributor to iAge is the chemokine CXCL9, which is shown to control endothelial cell senescence and function.
The authors show that glial AP1 is initially protective after traumatic brain injury (TBI) but remains active chronically, driving tau pathology and degeneration. Glial AP1 similarly activates with normal aging, suggesting this may be accelerated by TBI.
An economic analysis suggests that targeting aging offers potentially larger economic gains than eradicating individual diseases. Slowing aging to increase life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.
Facility-level factors associated with increased mortality rates among nursing home residents in Spain during the COVID-19 pandemic included a higher proportion of patients with complex diseases, lower scores on pandemic preparedness measures and higher COVID-19 incidence levels in the surrounding neighborhood.
Morshed et al. analyzed the proteome and phosphoproteome of brain tissue from patients with Alzheimer’s disease. The analysis of patient heterogeneity links glia pathologies and signaling pathways to stages of disease progression.
The authors present the results of a 24-month phase 2 study of AADvac1, a tau vaccine against Alzheimer’s disease. AADvac1 was safe and induced high levels of antibodies. In the whole study sample, there were no significant changes on clinical outcomes.
This study shows that APOE4, one of the largest genetic risk factors for Alzheimer’s disease, promotes advanced-stage vascular dysfunction and neurodegeneration in old mice via activation of the cyclophilin A pathway in pericytes and independently of the presence of amyloid-β.
Walker et al. report a proteome-wide association study that identifies 38 candidate proteins in nondemented older adults that are associated with future dementia risk. Pathway analysis of these proteins implicates immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.
Senescent cells and their production of inflammatory cytokines (senescence-associated secretory phenotype) affects aging and disease, including cancer. Zhang et al. report that epigenomic remodeling by KDM4 controls the senescence-associated secretory phenotype, and KDM4 expression by stromal cells of the tumor microenvironment promotes prostate cancer.
Arthur et al. report the biochemical and proteomic (SomaLogic) profiling of plasma and CyTOF immunophenotyping of peripheral blood mononuclear cells from 71 individuals with COVID-19 or other inflammatory pulmonary diseases, and 148 healthy donors aged 25–80 years old. The Resource reveals unique determinants of COVID-19 disease relative to healthy aging and other pulmonary disorders.
Aging, inflammation and senescence are controlled by NFκB. Cai and Han identify by comparative genomics a family of lncRNAs that are increasingly expressed during aging by NFκB-driven transcription, and find that many of these aging-associated lncRNAs regulate NFκB activity in turn.
In a cohort of older men from the Veterans Affairs Normative Aging Study, exposure to fine particulate matter (PM2.5), over just a few weeks and under levels considered hazardous, was found to impede cognitive function in older adults, but the adverse effects were lessened in people taking nonsteroidal anti-inflammatory drugs.
The authors show that exosomal transfer of osteoclast-derived microRNAs to chondrocytes decreases the resistance of cartilage to matrix degeneration, angiogenesis and sensory innervation, and promotes osteoarthritis progression in mice.
Aging is accompanied by structural and functional alterations of the central nervous system (CNS). Here, the authors show that cytotoxic CD8+ T cells accumulate in the CNS during normal aging, leading to axonal damage and contributing to age-related cognitive and motor decline.
Microglia can help clear amyloid β plaques in the Alzheimer’s disease brain but may also become dysfunctional and can contribute to disease progression. March-Diaz et al. reveal that hypoxia, a potentially modifiable risk factor for Alzheimer’s disease, disrupts the metabolism and function of microglia near plaques, which may contribute to neuropathology.
Using genetic and demographic data from the UK Biobank, the authors clustered 116 common diseases based on their age-of-onset profiles and found increased genetic similarity within clusters, suggesting common etiologies. Two of the four disease clusters were associated with aging-related genes but differed in functional enrichment and evolutionary profiles.
This study demonstrates that short and dysfunctional telomeres sensitize kidneys to develop fibrosis and enhance the genetic program associated with epithelial-to-mesenchymal transition in two mouse models of kidney fibrosis.
The authors found that the olfactory perception of food abundance can regulate the impact of dietary restriction on longevity in Caenorhabditiselegans. They show that food odors act on olfactory circuitry that signals the gut via octopamine to suppress dietary restriction-induced longevity.
Ito et al. show that regeneration in the aging brain is impaired due to reduced expression of the apelin receptor APJ. Circulating apelin signals oligodendrocytes via APJ to support remyelination, and this pathway can be restored in older mice with an APJ agonist.
A cohort study tracking 20-year age-related declines in multiple organ systems finds that, already by midlife, those aging fastest showed cognitive declines, signs of brain aging, diminished sensory–motor function and negative views about aging.