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For years, calcium and vitamin D supplements have been promoted as a simple way for older adults to protect their bones and prevent falls. But a massive review of nearly 154,000 people found that calcium, vitamin D, or a combination of both provided little to no meaningful protection against fractures or falls for most older adults.

A large-scale study suggests that men with higher levels of the amino acid tyrosine may have shorter lifespans, potentially losing close to a year of life expectancy. The finding is especially intriguing because tyrosine is commonly associated with brain health and is often used in supplements aimed at boosting focus and performance.

Quantitative insights into brain metabolism are essential for advancing our understanding of the energy dynamics in the brain. Here, we present a nanowatt-resolution biocalorimeter capable of real-time metabolic heat output measurements of individual, live Drosophila melanogaster brains. Using this platform, we show that female brains, across multiple genotypes, exhibit a significantly higher metabolic rate (∼10%-15%) than male brains at a young age (<10 days old) and follow distinct metabolic...

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that has been related to abnormal functional connectivity across motor, cognitive, and limbic networks. However, it remains unclear how directional (i.e., effective) connectivity between various networks is altered by an actual FOG-related motor imagery task. Twenty-four individuals with PD (11 freezers and 13 non-freezers) and 15 healthy controls underwent functional MRI. Participants performed a motor imagery task...

Parkinson's disease leads to a spectrum of locomotor deficits that vary in severity with the nature of daily activities and the fluctuating physiology of patients. Many of these deficits remain inadequately addressed by existing deep brain stimulation therapies that rely on activity-agnostic parameters optimized for cardinal motor symptoms. By contrast, therapies embedding activity-specific parameters have the potential to better address the entire range of symptoms. Here we expose physiological...

A randomized crossover study of five patients with Parkinson's disease (PD) demonstrates that gait-synchronized adaptive deep brain stimulation is feasible and safe, and reduces falls compared with continuous stimulation. Gait dysfunction in PD is a major source of disability and is often insufficiently treated by continuous deep brain stimulation (cDBS). Although adaptive DBS (aDBS) has shown efficacy for other motor symptoms using β-based, state-driven neural signals, gait is a dynamic,...

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more...

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Aging tissues experience a gradual decline in perfusion and metabolic resilience due to complex interactions among extracellular matrix (ECM) remodeling, vascular dysfunction, and mitochondrial impairment. Stiffening of the ECM that results from collagen crosslinking, elastin loss, and basement membrane thickening reduces vascular compliance and impairs local angiogenesis. The consequent reduction in capillaries and diminished endothelial reactivity leads to ongoing or intermittent hypoxia,...

Quantitative insights into brain metabolism are essential for advancing our understanding of the energy dynamics in the brain. Here, we present a nanowatt-resolution biocalorimeter capable of real-time metabolic heat output measurements of individual, live Drosophila melanogaster brains. Using this platform, we show that female brains, across multiple genotypes, exhibit a significantly higher metabolic rate (∼10%-15%) than male brains at a young age (<10 days old) and follow distinct metabolic...

Aging is the primary risk factor for most chronic diseases, and the global rise in aging populations presents an escalating challenge due to functional decline and multimorbidity. Gene therapy provides a versatile framework for modulating aging-regulatory pathways, such as epigenetic regulation, telomere maintenance, and stress-response networks, with the potential to reshape aging trajectories. In this review, we provide an in-depth synthesis of the genetic and epigenetic determinants of aging...

The human immune system undergoes dynamic remodeling from infancy through old age. We profiled PBMCs from 167 healthy individuals (ages 2 months to 105 years): infants (n = 36), children (n = 26), adolescents (n = 20), young adults (n = 24), middle‑aged (n = 16), older adults (n = 33) and oldest old (n = 12) using scRNA‑seq and snATAC‑seq (n = 23). MAIT and γδ T cells showed a "rise and fall" pattern, rising in childhood, peaking in young adulthood, and declining with age. Conventional CD8⁺ T...

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more...

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular 'clocks' to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

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Mitochondrial endonuclease G (EndoG) is involved in several important cellular processes and has been implicated in multiple diseases. Accordingly, molecules modulating EndoG activity may have high therapeutic potentials. Searching for compounds affecting paternal mitochondrial elimination (PME) in Caenorhabditis elegans, we have identified resveratrol (RSV), a well-known natural compound, as a PME inhibitor. Interestingly, RSV exists as a mixture of trans- and cis-isomers, which interconvert...

The brain and body undergo coordinated changes throughout the life span, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to aging and peripheral biomarkers of metabolic and vascular function, including body mass index, blood pressure, and blood biochemistry. We use multivariate pattern learning to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and...

Hypoxia is a common stress encountered by animal tissues during development, physiology, and disease. To cope with hypoxic stress, cells remodel metabolic and signaling networks to preserve viability and function. Lysosomes serve as central hubs for metabolic control and intracellular signaling, yet their role in hypoxic adaptation remains unclear. Here, we identify the lysosomal calcium transporter TMEM165 as a hypoxia-responsive regulator of cellular homeostasis. Under hypoxic conditions,...