Aging & Longevity

Aging is a primary risk factor for chronic diseases, with cellular senescence as an effective target to delay, prevent or alleviate age-related disorders. Here we report in vitro screening outputs from a natural medicinal agent library, wherein dihydromyricetin, a natural flavonoid, showed senotherapeutic potential. Dihydromyricetin protects senescent fibroblasts against further DNA damage and attenuates the senescence-associated secretory phenotype, acting as a senomorphic agent. Proteomics...

Covalent organic frameworks containing periodic redox-active motifs and conjugation structures are booming as competitive negative electrodes for ammonium-ion batteries. Introducing substantial single-electron active motifs linked by dynamic imine bonds can increase their capacity; however, this design is constrained by suboptimal single-electron redox efficiency and insufficient linkage stability. Here we unlock a multiple two-electron-transfer nitrobenzothiadiazole covalent organic framework...

Different types of dietary restriction (DR) have been practiced by humans for religious and medical purposes for millennia, but only during the past three decades has the scientific study of DR at cellular and molecular levels proliferated. Here we review the evidence testing a variety of DR paradigms in the context of aging, focusing on mammalian findings. We discuss potential DR mimetics that modulate autophagy, FGF21, AMPK, mTORC1, NAD^(+) metabolism, SIRTs, GLP-1R and other pathways as well...

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Aging involves multiple detrimental changes in the systemic milieu, leading to functional deterioration and age-related diseases. However, the potential self-protective adaptive alterations during aging remain underexplored. Here we show that phosphoenolpyruvate (PEP), a glycolytic metabolite, acts as a protective factor against age-related chronic inflammation. Longitudinal analyses in mice and humans reveal a biphasic PEP trajectory, characterized by initial accumulation followed by...

Cerebral small vessel disease (SVD) is a leading cause of stroke and dementia and yet is often an incidental finding in aged patients due to the inaccessibility of brain vasculature to imaging. Animal models are important for modelling the development and progression of SVD across the lifespan. In humans, reduced FOXF2 is associated with an increased stroke risk and SVD prevalence in humans. In the zebrafish, foxf2 is expressed in pericytes and vascular smooth muscle cells and is involved in...

Increasing health inequalities among older adults globally illustrate the urgent need for effective interventions. Socio-economic position (SEP), which reflects an individual's social and economic standing, may affect healthy ageing through various life course mechanisms. However, longitudinal associations between life course SEP and healthy ageing as a multidimensional construct remain unclear. We conducted a comprehensive systematic review of longitudinal studies investigating the associations...

Retinal age gap (RAG)-the difference between retina-predicted age and chronological age-indicates biological ageing that has been linked to the risk of mortality and chronic disease. We aimed to identify risk factors associated with higher RAG in an Australian population. This cross-sectional study included 5107 participants from the Busselton Healthy Ageing Study (BHAS), a Western Australian community-based cohort. Retinal age was estimated using a validated deep-learning model applied to...

MS4A4A and MS4A6A are microglia-expressed genes linked to Alzheimer's disease risk. In this issue of Neuron, Rosner et al.¹ show that these proteins cooperatively restrain TREM2 signaling, dampening protective microglial responses and highlighting MS4A inhibition as a potential strategy to rejuvenate the brain's innate immune system in Alzheimer's disease.

Age-related circadian disruptions accelerate physiological decline and shorten lifespan. Enhancing circadian amplitude has emerged as a promising strategy for ameliorating age-associated disorders. Here, we show that the circadian-phase-optimized administration of 3'-deoxyadenosine (3dA) strengthens circadian amplitude in hypothalamic paraventricular nucleus (PVN) neurons, mitigates aging biomarkers, and extends mouse lifespan. 3dA restores clock synchrony and hormonal rhythms, including...

Sleep architecture and continuity deteriorate markedly with aging, yet these changes are frequently approached as isolated sleep disorders rather than as manifestations of systemic biological dysregulation. Accumulating evidence indicates that age-related sleep fragmentation reflects the progressive disruption of interconnected metabolic, inflammatory and circadian networks that are central to the biology of aging. In this context, sleep can be more accurately interpreted as a functional readout...

Sarcopenia is a major health concern in aging populations. Resistance training (RT) is widely recommended to improve muscle mass, strength, and physical function in older adults. In recent years, research on both biological mechanisms and clinical effects of RT has increased. However, these two fields have largely progressed in parallel, with limited evidence linking biological mechanisms to clinical efficacy. This narrative review integrates preclinical and clinical mechanistic evidence on RT...

Geriatricians have struggled to describe a complex and sometimes ambiguous professional identity. Unlike other medical specialties anchored in discrete organ systems, diagnostic and interventional technologies, or clearly defined clinical settings, geriatric medicine encompasses the care of a heterogeneous population of older adults with widely varying clinical needs, priorities, and trajectories relevant to function, multimorbidity, and complexity. This Special Article examines four distinct...

Vascular aging is the accumulation of functional and structural changes of vessels throughout life. While earlier studies have shown that single manifestation of vascular aging is associated with an increased risk of cardiovascular disease (CVD), it is unknown how the different manifestations of vascular aging cluster at the individual level, and whether individuals with different vascular aging patterns have different risk of progression to overt CVD. Here, we identify three patterns of...

The hippocampus is crucial to learning and memory, functions that decline with age due to impaired mitochondrial bioenergetics and reduced mitophagy, resulting in the accumulation of dysfunctional mitochondria and increased susceptibility to neurodegeneration. Urolithin A (UA), a natural mitophagy activator derived from polyphenols, has demonstrated benefits in Alzheimer's disease models; however, its role in normal aging remains unclear. Here, we investigated whether UA can prevent or reverse...

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CONCLUSIONS: These findings support the integration of GDF-15 into precision geriatric care, though further longitudinal and interventional studies, including those evaluating the incremental value of adding GDF-15 to existing screening tools for frailty, sarcopenia, and functional status, are required to establish its clinical utility.

Cellular senescence contributes to aging and age-related diseases. Deep identifications of the senescence-specific cellular features are crucial to the better understanding of the survival and maintenance of senescence and the development of novel senolytics against senescent cells. By a global proteomic profiling of senescent human BJ fibroblasts induced by ionizing radiation, 178 cellular proteins with at least 4-fold or greater changes in abundance were identified, representing the cellular...

Recent advancements in Alzheimer's disease (AD) therapeutics have validated the use of amyloid beta (Aβ)-clearing antibodies, which reduce Aβ pathology but leave other disease hallmarks largely unaddressed. Since AD involves multiple pathological processes, additional strategies are needed to target complementary mechanisms. One such target is autophagy, a lysosomal mediated degradation pathway essential for cellular homeostasis that removes toxic protein aggregates and damaged organelles. This...

CONCLUSION: Polypharmacy and hyperpolypharmacy remain highly prevalent among older adults in the U.S., with a significant growth in medication expenditures over time among those with hyperpolypharmacy. These findings highlight the critical need for ongoing monitoring and tailored prescribing optimization efforts targeting subgroups with the high prescribing burden to reduce the clinical and economic burdens of polypharmacy and hyperpolypharmacy in aging populations.