Volume 1 Issue 1, January 2021

Actions are needed by national and local governments, businesses and community organizations to rise to the challenge of the age shift as part of the UN Decade of Healthy Ageing.

Non-traditional model organisms can facilitate discovery when their natural properties provide insight into biological mechanisms that are invariant across standard-use lab species. Long-lived naked mole-rats provide such insights for healthy aging.

Recent advances in deep learning enabled the development of AI systems that outperform humans in many tasks and have started to empower scientists and physicians with new tools. In this Comment, we discuss how recent applications of AI to aging research are leading to the emergence of the field of longevity medicine.

As a physician scientist caring for older adults in New York City during the peak of the COVID-19 pandemic, I reflect on my experiences, the stark contrast in resource availability between hospitals and nursing homes, and the scientific opportunities and challenges for aging research.

The COVID-19 pandemic highlights how elder-care facilities have failed to protect older adults in many countries — investing in home care while also reimagining facility-based models is required.

The increase in multidisciplinary research in the field of aging has many benefits and should be further applied to better understand and possibly reverse the stalled increase in life expectancy as well as growing social inequalities in life expectancy in many countries.

The NIA (part of the NIH) is one of the leading funders of aging and age-related disease research worldwide. Last fall, Nature Aging spoke to Luigi Ferrucci, its Scientific Director since 2011, to get his thoughts on the field and learn about the institute’s agenda and future plans for intramural and extramural aging research.

An extensive multiomic resource using human monocytes reveals large-scale remodeling of DNA methylation landscapes in healthy aging and accelerated or pathological aging contexts. This work provides an invaluable resource with important implications for the study of age-related changes in immune function.

The human gut microbiota is comprised of a vast assortment of trillions of microbial cells belonging to hundreds of different species, differing substantially between individual hosts. A new study has systematically investigated the relationship of host age to gut microbes in a geographically restricted and ethnically homogeneous human cohort, revealing key differences across ages and sexes.

Chambers et al. show that senescent skin cells in older adults provoke monocyte-dependent local inflammation in response to injury, which hampers T cell recall responses to viruses. Importantly, they further show that this phenomenon can be blocked pharmacologically to boost adaptive immunity.

Accurate blood tests for Alzheimer’s disease (AD) are critical tools that have the potential to revolutionize dementia research, clinical trials and clinical care. Models combining blood-based biomarkers that represent multiple aspects of AD brain pathology with key individual level factors may improve prediction of AD dementia.

In this Perspective, Rando and Wyss-Coray discuss recent advances in the field of the biology of aging, focusing on new concepts related to the processes of cell and tissue aging and how they impact the healthspan and lifespan of an individual.

Linda Fried and colleagues argue that physical frailty reflects the dysregulation of a complex dynamical system underpinning health and resilience, and discuss the implications for new prevention and treatment approaches.

Intermittent and periodic fasting are emerging as important interventions with the potential to extend longevity and healthspan. This Review discusses how they affect longevity and healthspan in model organisms and humans, their connection to major nutrient-sensing signaling pathways and the importance of refeeding.

The authors identify the evolutionarily conserved amino acid-sensing protein Sestrin as a key mediator of dietary restriction benefits in flies. Sestrin regulates gut stem cell activity via the TOR pathway, resulting in improved gut health and longevity.

The authors find that mice fed a diet with reduced levels of branched-chain amino acids have improved metabolic health, and in males but not females, lifelong feeding of such a diet reduces frailty and extends life span.

Using metagenomics sequencing, Zhang et al. examined sex- and age-dependent trajectories of the gut microbiota in four cohorts across China, Israel and the Netherlands. The authors found age-related gut microbial trajectories common across all populations, with the abundance of Streptococcus gordonii predicting chronological age.

The authors show that cutaneous immunity is attenuated during aging due to the recruitment, by senescent fibroblasts, of inflammatory monocytes, which in turn inhibit resident memory T cell activation. Inhibition of p38 MAPK signaling blocks the recruitment and function of these monocytes and restores immunity.

This study shows that combinations of blood-based biomarkers can be used to predict cognitive decline and dementia due to Alzheimer’s disease in patients with mild cognitive impairment. Biomarkers for tau and neurodegeneration provided accurate prognosis of decline and conversion over four years.

Multiomics profiling of circulating monocytes from young and older healthy males reveals key determinants of healthy aging, including regions of age-associated DNA hypo- and hypermethylation, cellular chromatin landscape and effect on gene expression.