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Aging is the main determinant of chronic diseases and mortality, yet organ-specific aging trajectories vary, and the molecular basis underlying this heterogeneity remains unclear. To elucidate this, we integrated genomic, epigenomic, transcriptomic, proteomic, and metabolomic data, employing post-genome-wide association study methodologies to systematically investigate the molecular mechanisms of nine organ-specific aging clocks and four blood-based epigenetic clocks. We uncovered genetic...

CONCLUSIONS: The findings of this cross-sectional study suggested that differential marital status has a variable impact on the risk of developing age acceleration, with significant gender differences. All indications are that men benefit more from marriage in the aging process, which is food for thought.

Mitochondrial dysfunction is a central driver of cellular senescence, a core hallmark of aging. While intrinsic mechanisms have been extensively reviewed, this article offers a novel paradigm by emphasizing the critical role of interorganellar communication in mitochondria-mediated senescence. We present a systematic dissection of the molecular mechanisms underlying functional crosstalk between mitochondria and key organelles, including the endoplasmic reticulum (ER), lysosomes, and peroxisomes....

Mitochondrial protein homeostasis (proteostasis) keeps the mitochondrial proteome functional. Thus, proteostasis is essential for mitochondrial activity and overall cellular functions, and a reduction in its function corresponds with diseases and aging in humans. Recent studies in various model organisms highlight components and mechanisms of mitochondrial proteostasis from biogenesis, through assembly, to turnover. Key findings include the identification of new components and mechanistic...

Creative experiences may enhance brain health, yet metrics and mechanisms remain elusive. We characterized brain health using brain clocks, which capture deviations from chronological age (i.e., accelerated or delayed brain aging). We combined M/EEG functional connectivity (N = 1,240) with machine learning support vector machines, whole-brain modeling, and Neurosynth metanalyses. From this framework, we reanalyzed previously published datasets of expert and matched non-expert participants in...

Across species, spatial memory declines with age, possibly reflecting altered hippocampal and medial entorhinal cortex (MEC) function. However, the integrity of cellular and network-level spatial coding in aged MEC is unknown. Here, we leveraged in vivo electrophysiology to assess MEC function in young, middle-aged, and aged mice navigating virtual environments. In aged grid cells, we observed impaired stabilization of context-specific spatial firing, correlated with spatial memory deficits....

Alzheimer's disease is a specific neurodegenerative disorder, distinct from normal aging, with a growing unmet medical need. It is characterized by the accumulation of amyloid plaques in the brain, primarily consisting of amyloid beta (Aβ) fibrils. Therapeutic antibodies can slow down the disease, but are associated with potential severe side effects, motivating the development of small molecules to halt disease progression. This study investigates the interaction between the clinical drug...

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Neuroimaging and machine learning are advancing research into the mechanisms of biological aging. In this field, 'brain age gap' has emerged as a promising magnetic resonance imaging-based biomarker that quantifies the deviation between an individual's biological and chronological age of the brain. Here we conducted an in-depth genomic analysis of the brain age gap and its relationships with over 1,000 health traits. Genome-wide analyses in up to 56,348 individuals unveiled a heritability of...

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Sarcopenia, the progressive loss of skeletal muscle mass and function with aging, is a growing public health concern. Conventional treatments such as exercise, pharmacological agents, and nutritional support offer limited efficacy, especially in older populations with reduced mobility or comorbidities. This study aimed to evaluate low-intensity pulsed ultrasound (LIPUS) as a novel, non-invasive therapeutic approach for age-related muscle atrophy. LIPUS was applied to the right hindlimbs of young...

Mitochondrial homeostasis relies on a tight balance between mitochondrial biogenesis and degradation. Although mitophagy is one of the main pathways involved in the clearance of damaged or old mitochondria, its coordination with mitochondrial biogenesis is poorly characterized. Here, by unbiased approaches including last-generation liquid chromatography coupled to mass spectrometry and transcriptomics, we identify the protein phosphatase PP2A-B55α/PPP2R2A as a Parkin-dependent regulator of...

Complex diseases often exhibit sex dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex dimorphisms during aging with distinct patterns of change in...

Complex diseases often exhibit sex dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex dimorphisms during aging with distinct patterns of change in...

The ability to sense and adapt to adverse food conditions is essential for survival across species, but the detailed mechanisms of neuron-digestive crosstalk in food sensing and adaptation remain poorly understood. Here, we identify a novel mechanism by which Caenorhabditis elegans detect unfavorable food sources through neurons and initiate a systemic response to shut down digestion, thus safeguarding against potential harm. Specifically, we demonstrate that NSY-1, expressed in AWC neurons,...

DNA and historical sleuthing have traced the extinct bird’s remains to a museum in Ohio