Reviews & Analysis

Cellular senesence is believed to be a driver of aging. We designed and synthesized a photosensitive prodrug that destroys senescent cells by integrating multiple technologies that combine biomarker guidance with a fluorescence tag, target-site anchoring and photodynamic therapy, providing a strategy for monitoring and specifically eliminating senescent cells to regulate aging.

Age-related decline in brain health is associated with poor blood flow and limitations in energy supply, although the vascular mechanisms are poorly understood. We report an age-related decrease in responsivity of brain microvessels, accompanied by a decrease in vessel density and loss of vascular mural cell processes.

Mitochondrial dysfunction is central in biological aging, but experimentally controlling mitochondria in vivo to test causality has been difficult. Optogenetically preserving mitochondrial function with age addressed this difficulty and increased lifespan and healthspan in Caenorhabditis elegans.

Neuroinflammation is increasingly recognized as an important pathological trigger for the development and progression of Alzheimer’s disease. However, the molecular mechanism remains largely unclear. We identify activation of the neuroimmune cGAS–STING signaling pathway as a critical molecular link, predominantly in microglia, that contributes to Alzheimer’s disease pathogenesis.

Brain functions and connectivity patterns related to maladaptive emotion regulation are poorly understood. We find that, in older adults subjected to high emotional events, functional connectivity between the default mode network and the amygdala is associated with higher anxiety, rumination and negative thoughts.

Aging is known to exacerbate atherosclerosis, but the mechanisms have been largely unknown. A study in Nature Aging reveals a bone-marrow-controlled axis of clonality during atherosclerosis, showing that aged bones drive an inflammatory milieu that promotes smooth muscle polyclonality and the formation of larger lesions.

Mating is known to accelerate the aging of the opposite sex in a variety of species. A transcriptomic analysis of extracted germlines from mated and unmated Caenorhabditis elegans by Shi and Murphy now identifies a Piwi-interacting RNA-to-Hedgehog signaling pathway that regulates the accelerated aging of hermaphrodites.

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.