Articles in 2022

Under conditions of stress, autophagic degradation of nuclear and nucleolar components was found to promot.e youthfulness and delay aging by preserving nuclear architecture and preventing nucleolar expansion, in somatic cells. We also found that nuclear-material autophagy serves as an essential quality-control mechanism that contributes to sustaining germline immortally.

We found that aging is accompanied by a reduction in cardiomyocyte nuclear size and increased stiffness, dependent on loss of A-type lamins. Mechanistically, age-dependent nuclear remodeling represses expression of cardiogenic transcription factors that are required for heart contractility. Preserving lamin or transcription factors delays cardiac decline.

Using light to optogenetically power mitochondria, this study shows that opposing the age-related decline in mitochondrial membrane potential leads to increased healthspan and lifespan in Caenorhabditis elegans. This result points to mitochondrial charge as a fundamental regulator of biological aging.

The authors show that liver sinusoidal endothelial cell (LSEC) senescence promotes steatosis by reprogramming liver endothelial zonation and inhibiting C-kit, a type III receptor tyrosine kinase. Infusing C-kit-expressing LSECs in aged or diet-induced NASH mice counteracts senescence and steatosis.

Nuclear morphology changes with aging, but the role of these changes and the underlying mechanisms are not fully understood. The authors find that the nuclear envelope anchor protein ANC-1 in worms, and its counterpart nesprin-1 and nesprin-2 in mammals, promotes the degradation of nuclear components to limit nucleolar size and function in a soma longevity and germline immortality mechanism.

In this Perspective, the authors discuss experimental scenarios that breach the assumption of independence of all samples or participants in a study, specifically in aging research. They outline various strategies to improve the rigor and accuracy of the science with design and analysis solutions, while also considering real-world constraints.

Spermidine is a naturally occurring polyamine that elicits geroprotection and autophagy induction across species. This Review delineates its molecular targets, effects on the hallmarks of aging, and recent insights from epidemiological and clinical studies.

Kirkland et al. identify conserved age-dependent nuclear remodeling in Drosophila cardiomyocytes, dependent on declining Lamin C. They show that Lamin C loss induces reversible heart dysfunction by repressing myogenic transcription factors.

This Perspective lays out the impetus and goals of the Cellular Senescence Network established to comprehensively identify and characterize senescent cells (SnCs) across tissues and lifespan, providing a publicly available SnC atlas.

Single-cell transcriptomic data from a neurogenic region of the mouse brain were used to build aging clocks for specific neural cell types. These clocks showed that heterochronic parabiosis and exercise lead to distinct transcriptomic rejuvenation patterns across cell types.

There are no current standard-of-care treatments for sarcopenia, an age-associated decline in muscle mass and strength. A new study shows that genetically or pharmacologically countering the age-associated accumulation of sphingolipids in skeletal muscle can ameliorate sarcopenia in mice. The authors also identify genetic variants linked to sphingolipid biosynthesis that associate with muscle function in aged humans.

The authors show that sphingolipids, a class of fat molecules, accumulate in skeletal muscle during aging. They demonstrate that reducing sphingolipids improves age-related fitness in mice by enhancing the myogenic response of muscle and present genetic evidence that these findings may also translate to humans.

The ovary is one of the first organs to functionally decline with age, leading to many deleterious consequences for health and well-being. A better understanding of ovarian aging through collaborative research and investments will play an important part in achieving healthy aging for all.

The authors found that, across tissues and in multiple datasets, aging is accompanied by a length-associated transcriptome imbalance. In most cases, a decrease in the relative abundance of long transcripts was observed and could be reversed by interventions targeting aging.

Mavrikaki et al. show that severe COVID-19 is associated with molecular signatures of aging and low cognitive performance in the human frontal cortex; and emphasize the value of neurological follow-up in recovered individuals.

The US National Academy of Medicine (NAM)’s first global grand challenge is dedicated to healthy longevity. We summarize the NAM’s Global Roadmap for Healthy Longevity, highlighting evidence that societies can benefit from untapped human, social and economic capital through investments throughout the life course.

Martínez Corrales et al. show that the activation of the conserved pro-longevity transcription factor FOXO solely in youth promotes subsequent health and survival in female fruit flies, via chromatin remodeling and induction of Xbp1.