Aging & Longevity

While mitochondria are recognized as promising therapeutic targets for common pathologies of aging, existing drug discovery platforms fail to capture the adequate physiological and biological contexts necessary to identify translatable, clinically-relevant leads. The goal of this study was to identify marine natural products that modulate mitochondrial function using a screening pipeline leveraging primary human cells in a cell-based phenotypic primary screen. Using this approach, we identified...

The anterior cingulate cortex (ACC) is particularly vulnerable to aging, which impairs cognitive functions such as attention and working memory. Although aging is known to alter intrinsic electrophysiological properties in other brain regions, the differences in the properties of aged ACC neurons and young adult neurons remain uninvestigated. In this study, we compared the intrinsic membrane properties and firing characteristics of aged layer 2/3 pyramidal neurons (26-month-old rats) with those...

CONCLUSION: These results show the impact of food insecurity and functional limitations and HRQOL in older adults. The results emphasize the urgent need for addressing food insecurity and promote healthy aging among older adults in New York City.

Young children are at increased risk for respiratory tract infections and are frequently colonized by respiratory pathogens. However, how the mucosal immune system differs between children and adults is relatively unknown. We collected nasal samples from 50 young children (aged 1-5 years) and 318 young adults (aged 18-34 years) to study how the mucosal immune system and host-microbe interactions differ with age. We used multi-omics data integration to combine host (immunophenotyping,...

Globally, the growing proportion of older individuals is imposing personal and societal costs. However, interventions that slow aging are possible; for example, dampened nutrient signaling pathway activity in animal models promotes better health later in life. Recent findings indicate that such interventions have long-term effects even when applied transiently in early adulthood, forming a "physiological memory." Similar memory has been extensively documented in human epidemiology, where the...

Aging is typically framed as a one-way, irreversible accumulation of molecular damage in cells and tissues, leading to progressive functional decline. Yet mammalian reproduction, and particularly female reproduction, reveals a striking exception to this rule. Despite residing within an aging organism and within a fast-aging ovarian tissue environment, oocytes give rise to embryos that begin life with restored developmental potential and youthful molecular organization. By reframing ovarian...

Maintaining balance requires a complex interplay between sensory and motor processes, and this ability deteriorates with age, impairing daily life activities and contributes to increased fall risks. Importantly, while cognitive-motor interference paradigms suggest an aging-related increase in the cortical involvement in balance regulation, direct evidence remains lacking. To clarify this issue, we assessed the effect of aging on sway-based corticokinematic coherence (CKC), which is a measure of...

Endogenous bioelectric currents regulate development and regeneration, but their influence on organismal longevity and stem cell-mediated repair is not well understood. We demonstrate that a brief, clinically safe pulse of electrical current (PEC) produces lasting rejuvenation in the colonial chordate Botryllus schlosseri. In this species where all differentiated tissues are replaced weekly and progenitor populations mediate the weekly de novo generation of new organs, organismal aging is...

The mitochondrial unfolded protein response (UPR^(mt)) protects mitochondria from proteotoxic stress. Current models induce acute and severe mitochondrial disruption and propose cytosolic detection following the release of mitochondrial damage signals into the cytosol. However, this mode of toxicity contrasts sharply with physiological stress, such as the gradual accumulation of reactive oxygen species (ROS) during aging or chronic respiratory chain defects. Here, we employ a chemogenetic...

Haematopoietic stem cells (HSCs) produce all blood and immune cells throughout life, but ageing progressively impairs their function, generating excessive myeloid and megakaryocyte cells at the expense of lymphocytes. This lineage imbalance contributes to immune decline, chronic inflammation and increased disease susceptibility in the elderly, yet the underlying mechanisms remain poorly understood. Here we show that a specific Meg3^(+) HSC subset...

Sex differences in ageing and lifespan are widespread across taxa, yet their evolutionary causes remain debated. A leading hypothesis proposes that such differences arise adaptively from sex-specific life-history trade-offs, but formal theoretical support is lacking. We therefore develop a mathematical model to examine how these trade-offs shape lifespan evolution across ecological and mating system contexts. Under monogamy, individuals optimise a survival-reproduction trade-off, mediated by...

Mitochondrial homeostasis is majorly maintained through mitochondrial autophagy (mitophagy). Recent research highlights the region- and cell type-specific nature of mitophagy during brain aging; however, these dynamics have largely remained unexplored in living brains. To address this gap, we conducted two-photon mt-Keima imaging in somatosensory cortical neurons and astrocytes in behaving male mice across two age groups, including 2-3-month-old (early-aged) and 18-20-month-old (old-aged) mice....

CONCLUSIONS: Undermined autonomy poses a significant independent threat to older adults' physical health and longevity. This detrimental effect is partly driven by the internalization of negative stereotypes regarding older adults' competence. Findings underscore the critical need to protect older adults' autonomy and challenge the infantilizing attitudes that often rationalize paternalistic practices.

Nearly two-thirds of Americans with Alzheimer's disease (AD) are women. Prior research suggested that women with AD have lower brain estrogen levels than those without AD. However, how estrogen deficiency modulates this sex-based difference in AD vulnerability is not well understood. Aromatase, the key enzyme for estrogen biosynthesis, is expressed in both neurons and astrocytes of the brain, including the hippocampus. This study aims to assess the mechanistic link between brain-selective...

Endogenous double-stranded RNAs (dsRNAs) are immunogenic self-molecules that drive aberrant immune activation under pathological conditions. Here, we show that dsRNAs and their regulation by RNA-binding proteins are key determinants of the fine balance between aging and immunity in Caenorhabditis elegans and cultured human cells. We find elevated levels of dsRNAs with organismal aging and cellular senescence. We identify a moonlighting function for phenylalanyl-tRNA synthetase, FARS-1/FARSA, as...

Time-restricted feeding (TRF), a circadian-based dietary intervention, has emerged as a promising strategy to counteract metabolic and age-related dysfunctions. However, how TRF can reverse stem cell aging and restore tissue regenerative potential remains unclear. In this study, we investigated the effects of long-term TRF on senescent adipose-derived stem cells (ADSCs) in a high-fat diet (HFD) induced aged mice model. Mice were assigned to standard or HFD diets under ad libitum or TRF (8 h/day)...

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline driven by amyloid-β plaques, tau neurofibrillary tangles, and extensive neuronal loss. Emerging evidence highlights mitochondrial dysfunction, defective mitophagy, and disrupted proteostasis as pivotal events in disease progression. Transglutaminase TG2, a multifunctional calcium-dependent enzyme, has gained attention for its capacity to link these pathological processes. Beyond...

Sepsis arises from a dysregulated immune response to infection, causing systemic inflammation and high mortality. Its nonspecific symptoms and complex molecular mechanisms make early diagnosis and therapeutic development challenging. The contribution of host factors to this heterogeneity is not fully understood. We investigated whether baseline gene co-expression networks are preserved or reorganized in sepsis and whether age and sex influence these networks by analyzing RNA-seq data from...

Inorganic CsPbI(3) perovskite, known for its high chemical stability and near-ideal bandgap, offers a promising solution to the instability of organic-inorganic hybrid perovskites that limit perovskite solar cells (PSCs) longevity. However, the conventional intermediate phase (dimethylammonium lead iodide, DMAPbI(3)) templating method suffers from inefficient phase conversion, hindering high-performance PSC development. To overcome this limitation, we engineered the crystallographic orientation...

While Life's Essential 8 (LE8) provides a comprehensive measure of cardiovascular health (CVH), its association with mortality among the oldest-old, including centenarians, remains unclear. This study evaluated the relationship between LE8-defined CVH and all-cause mortality across adulthood using data from the China Kadoorie Biobank (Hainan cohort) and the China Hainan Centenarian Cohort Study, including 31,473 individuals aged 30-116. Participants were categorized by life stage and CVH score...