Reviews & Analysis

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.

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.

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.

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.

In our aging global population and with no effective treatments, the cognitive impairments associated with Alzheimer’s disease represent a major healthcare problem. A recent study in Nature Aging highlights intermittent fasting as a potential way to decrease the progression of Alzheimer’s disease in mice through changes to the gut microbiota.

Aging is associated with an accumulation of myeloid-biased hematopoietic stem cells with reduced regenerative potential, but the underlying mechanisms remain unclear. A study by Wendorff et al. demonstrates that inactivation of a single epigenetic regulator — the plant homeodomain factor 6 (PHF6) — transcriptionally and functionally rejuvenates mouse aged hematopoietic stem cells.

On 27 and 28 June 2022, the UK SPINE network (www.kespine.org.uk) held an in-person conference focusing on how new medicines could contribute to improving healthspan (healthy life years). The event facilitated knowledge exchange within the broader geroscience community by bringing together researchers and stakeholders from multiple sectors, including industry, academia, entrepreneurs, small-to-medium-sized enterprises, regulators, patients and carers, investors and policy makers.

We used data from the Longitudinal Aging Study in India (LASI) to provide up-to-date epidemiological estimates of the prevalence of vision impairment among the Indian population. We find that older adults, and particularly women, marginalized groups and those from lower socioeconomic strata, had a higher prevalence of visual impairment.

Our longitudinal study comparing the skin, gut and oral microbiomes of community-dwelling older adults and nursing home residents showed striking changes known to be linked to antibiotic resistance and disease risk. Such shifts were associated with frailty, not chronological age, and were most pronounced in the skin, the primary reservoir for infection risk.

In this Perspective, Jan Vijg and Brandon Milholland discuss that at high ages the probability of survival becomes vanishingly small, presenting a soft limit to human lifespan. They elaborate on the mechanistic basis of the observed limit to maximum human lifespan, and on the seemingly impossible future developments required to circumvent the current limit.

A new study shows that decreased cystatin A synthesis in aged epidermis mediates age-related bone loss, whereas topical treatment that restores cystatin A mitigates this loss. This report demonstrates that skin aging has systemic consequences by showing that signals originating in skin can control bone function.

Elder abuse has been recognized as a serious problem for decades. Yet rigorous studies are rare. Burnes and colleagues move the field forward by identifying how pervasive the problem is, the factors that increase and decease vulnerability, and how these factors change over a three-year period.

While C. elegans males are known to induce demise of hermaphrodites, the mechanism underlying this phenomenon is poorly understood. Through transcriptomic analyses, Booth et al. identify specific hermaphrodite gene sets that respond to male pheromones, sperm and seminal fluid and can mediate premature death of hermaphrodites.

Carol Brayne and Terrie Moffit discuss the limitations of large-scale volunteer databanks (LSVD) for understanding aging and disease, call for further evaluation of their value and offer their thoughts on how to make the reporting of LSVD studies more transparent.

This Perspective describes the blueprint, challenges and potential solutions for the transformation of Alzheimer’s disease clinical care pathway with biomarker-guided and digitally facilitated detection and intervention at early disease stages.

Deep learning was applied to cellular images to predict senescence on the basis of nuclear morphology. These methods recognize senescence in diverse cell types, show increasing senescence with age in liver and dermis, and suggest that higher rates of senescence associate with several age-related diseases but reduced cancer risk.

Mouse frailty can be measured with a frailty index by manually counting health deficits. Vivek Kumar and colleagues use machine learning to extract physical performance deficits from video data to create a ‘visual frailty index’. This automated technique may facilitate high-throughput research into new frailty interventions.

Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in single cardiomyocytes from individuals across the human lifespan. Aged cardiomyocytes were found to have a higher burden of sSNVs and show mutational signatures that suggest failed repair of oxidative DNA damage.