Articles in 2021

The epigenetic mark H3K9me3 is associated with silencing of lineage-inappropriate genes. Here the authors show that some lineage-inappropriate genes are derepressed in senescent cells through physical decompaction of H3K9me3-heterochromatic regions.

Naked mole rat (NMR) is an exceptionally long-lived rodent species that on the phenotypic level seems to evade aging. Here the authors show that NMRs age epigenetically, while epigenetic clocks detect that NMR queens age more slowly than nonbreeding females.

As the end of 2021 approaches, Nature Aging’s editorial team reflects on our experience in the last two years of conferencing and introduces a calendar for conferences on aging and age-related diseases for 2022.

On 16 and 17 March 2021, the National Institute of Allergy and Infectious Diseases and the National Institute of Aging convened a virtual workshop to discuss developments in SARS-CoV-2 research pertaining to immune responses in older adults, COVID-19 vaccines in both aged animals and older individuals, and to gain some perspective on the critical knowledge gaps that need addressing to establish scientific priorities for future research studies.

Age is the greatest risk factor for Alzheimer’s disease and aging is associated with the shortening of telomeres, the terminal regions of chromosomes. A new study shows that somatic activation of telomerase reverse transcriptase protein, an enzyme that maintains telomere length, ameliorates Alzheimer’s-disease-related phenotypes in mouse models and neurons derived from human induced pluripotent stem cells.

Using a treatment that activates the peripheral immune system in an animal model of amyloidosis, the authors show that monocyte-derived macrophages can modify Alzheimer’s disease progression via a TREM2-independent mechanism.

In this Review, the authors discuss the concept of molecular damage in aging, from theoretical models to experimental approaches and how to test interventions targeting aging that reduce its burden.

This study shows that age-related cognitive decline is alleviated by heterochronic microbiota transplantation in mice and that δ-valerobetaine, a microbiota-derived metabolite that increases with age in both mice and humans, alters neuronal and cognitive processes.

The authors link neuronal expression of telomerase reverse transcriptase to amyloid pathology and cognitive dysfunction in preclinical models of Alzheimer’s disease.

With aging, the immune system undergoes severe changes that impact health in numerous ways. For a comprehensive, translational analysis of these alterations, Krishnarajah et al. here provide profiling of immune cell populations across 12 tissues from young and old mice.

In the era of big data, looking for insights in large datasets has become the norm — and health data are no exception. Combining systems-biology-driven, endophenotype-based analysis of drug targets with large-scale medical claims data points to sildenafil as a potential treatment opportunity for Alzheimer’s disease.

The authors developed a vaccine against a membrane-bound seno-antigen called GPNMB and show that it can be used as a new senolytic approach. The vaccine led to improvements of several age-related phenotypes and prolonged the lifespan of a progeroid mouse model.

Using a new computational approach to identify senescent cells from single-cell transcriptomic data, the authors find that most senescent cells in the human brain are excitatory neurons with elevated CDKN2D/p19 expression, which often display Alzheimer’s disease-associated tau pathology.

Age-friendly cities initiatives aim to facilitate active and healthy aging. Focusing on the urban physical environment, the authors argue that longevity-ready cities that aim for better health and well-being for people of all ages from a life-course perspective can accomplish more than initiatives focused solely on old age.

Aging-related changes in DNA methylation have been used to estimate the biological age of organisms and tissues. Measuring DNA methylation in single cells is notoriously difficult and current methods only yield sparse methylation profiles, but a new computational method now offers the capability of profiling biological age at single-cell resolution.

Epigenetic clocks emerged as crucial biomarkers of the aging process, but their use has so far been limited to bulk samples. Trapp et al. unveil a new statistical framework that enables epigenetic age profiling at single-cell resolution.

Exposure to young blood slows down aging of several organs and prevents physical, cognitive and immune decline. However, how circulating factors mediate these effects is poorly understood. In this issue of Nature Aging, Sahu et al.¹ describe a key role for circulating extracellular vesicles in regulating skeletal muscle regeneration during aging, through the shuttling of Klotho transcripts.

Using an in silico network-based discovery approach, the authors identified sildenafil as a repurposable drug for Alzheimer’s disease. Analyzing insurance claims data from over 7 million individuals, they found that sildenafil usage was associated with a reduced risk of Alzheimer’s disease diagnosis.

Circulating factors play an important role in tissue aging. Here, the authors show that serum EV subpopulations and cargoes remodel with age and that EVs from young mouse serum rejuvenate aged skeletal muscle.

The Longitudinal Aging Study in India (LASI), the largest national health and retirement study in the world, released its wave 1 microdata earlier this year. The principal investigators of LASI introduce the study and explain how it can advance aging research in India and beyond in response to the impending challenges of rapid population aging.