A5015536873- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Telomeres, Telomerase, and Senescence
- Adipose Tissue and Metabolism
- Spaceflight effects on biology
- Epigenetics and DNA Methylation
- Stress Responses and Cortisol
- Identity, Memory, and Therapy
- Kruppel-like factors research
- Climate Change and Health Impacts
- Diet and metabolism studies
- Mental Health Research Topics
- Functional Brain Connectivity Studies
- Tryptophan and brain disorders
- Health, Environment, Cognitive Aging
- Fibroblast Growth Factor Research
Columbia University Irving Medical Center
2022-2025
Chronic psychosocial stress increases disease risk and mortality, but the underlying mechanisms remain largely unclear. Here we outline an energy-based model for transduction of chronic into over time. The energetic allostatic load (EMAL) emphasizes cost allostasis load, where "load" is additional burden required to support stress-induced energy needs. Living organisms have a limited capacity consume energy. Overconsumption by brain-body processes leads hypermetabolism, defined as excess...
Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic results in load, dysregulated state predicts functional decline, accelerates aging, and increases mortality humans. The energetic cost cellular basis for damaging effects load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find glucocorticoid...
Abstract FGF21 is a metabolic hormone induced by fasting, stress, and mitochondrial oxidative phosphorylation (OxPhos) defects that cause diseases (MitoD). Here we report acute psychosocial stress alone (without physical exertion) decreases serum an average of 20% ( p <0.0001) in healthy controls but increases 32% people with MitoD—pointing to functional interaction between the response OxPhos capacity regulating FGF21. We further define co-activation patterns stress-related...
Abstract Human blood contains cell-free mitochondrial DNA (cf-mtDNA) that dynamically increases in concentration response to acute mental stress. Like other neuroendocrine stress markers, we previously found cf-mtDNA is also detectable saliva, calling for studies examining saliva reactivity In healthy women and men from the MiSBIE (Mitochondrial Stress, Brain Imaging, Epigenetics) study (n=68, 66% women), a brief socio-evaluative stressor induced striking 280% or 2.8-fold increase within 10...
Abstract Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic results in load, dysregulated state predicts functional decline, accelerates aging, and increases mortality humans. The energetic cost cellular basis for damaging effects load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find...
Health emerges from coordinated psychobiological processes powered by mitochondrial energy transformation. But how do mitochondria regulate the multisystem responses that shape resilience and disease risk across lifespan? The Mitochondrial Stress, Brain Imaging, Epigenetics (MiSBIE) study was established to address this question determine influence interconnected neuroendocrine, immune, metabolic, cardiovascular, cognitive, emotional systems among individuals spanning spectrum of...
ABSTRACT To understand how organisms age, we need reliable multimodal molecular data collected at high temporal resolution, in specific cell types, across the lifespan. We also interpretative theory that connects aging with basic mechanisms and physiological tradeoffs. Here leverage a simple cellular replicative system combined mathematical to address organismal aging. used cultured primary human fibroblasts from multiple donors molecularly energetically profile entire effective lifespans of...