James Patrick White Jr.

Journal Article Nature aging · February 2025 Caloric restriction (CR) slows biological aging and prolongs healthy lifespan in model organisms. Findings from the CALERIE randomized, controlled trial of long-term CR in healthy, nonobese humans broadly supports a similar pattern of effects in humans. To ... Full text Cite

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-RKT.

Journal Article Cell Rep · March 26, 2024 An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274 ... Full text Link to item Cite

Multi-omic rejuvenation and life span extension on exposure to youthful circulation

Journal Article Nature Aging · August 1, 2023 Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment ... Full text Cite

Biological age is increased by stress and restored upon recovery.

Journal Article Cell Metab · May 2, 2023 Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report ... Full text Link to item Cite

Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling.

Journal Article Nat Commun · December 9, 2022 Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in f ... Full text Link to item Cite

The role of Meteorin-like in skeletal development and bone fracture healing.

Journal Article J Orthop Res · November 2022 Meteorin-like protein (Metrnl), homologous to the initially identified neurotrophic factor Meteorin, is a secreted, multifunctional protein. Here we used mouse models to investigate Metrnl's role in skeletal development and bone fracture healing. During de ... Full text Link to item Cite

Phosphoproteomic mapping reveals distinct signaling actions and activation of muscle protein synthesis by Isthmin-1.

Journal Article Elife · September 28, 2022 The secreted protein isthmin-1 (Ism1) mitigates diabetes by increasing adipocyte and skeletal muscle glucose uptake by activating the PI3K-Akt pathway. However, while both Ism1 and insulin converge on these common targets, Ism1 has distinct cellular action ... Full text Link to item Cite

Career pathways, part 6.

Journal Article Nature metabolism · October 2021 Full text Cite

Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review.

Journal Article J Am Coll Cardiol · September 14, 2021 Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan diso ... Full text Link to item Cite

The AMPK/p27Kip1 Pathway as a Novel Target to Promote Autophagy and Resilience in Aged Cells.

Journal Article Cells · June 8, 2021 Once believed to solely function as a cyclin-dependent kinase inhibitor, p27Kip1 is now emerging as a critical mediator of autophagy, cytoskeletal dynamics, cell migration and apoptosis. During periods of metabolic stress, the subcellular location of p27Ki ... Full text Link to item Cite

Amino Acid Trafficking and Skeletal Muscle Protein Synthesis: A Case of Supply and Demand

Journal Article Frontiers in Cell and Developmental Biology · May 31, 2021 Skeletal muscle protein synthesis is a highly complex process, influenced by nutritional status, mechanical stimuli, repair programs, hormones, and growth factors. The molecular aspects of protein synthesis are centered around the mTORC1 complex. However, ... Full text Cite

Chronic caloric restriction maintains a youthful phosphoproteome in aged skeletal muscle.

Journal Article Mech Ageing Dev · April 2021 Caloric restriction (CR) can prolong aged skeletal muscle function, yet the molecular mechanisms are not completely understood. We performed phosphoproteomic analysis on muscle from young and old mice fed an ad libitum diet, and old mice fed a CR diet. CR ... Full text Link to item Cite

Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of inflammatory arthritis.

Journal Article J Appl Physiol (1985) · March 1, 2021 Rheumatoid arthritis (RA) is a systemic inflammatory arthritis impacting primarily joints and cardiac and skeletal muscle. RA's distinct impact on cardiac and skeletal muscle tissue is suggested by studies showing that new RA pharmacologic agents strongly ... Full text Link to item Cite

Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · August 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · March 2020 The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regu ... Full text Link to item Cite

AGS and NIA Bench-to Bedside Conference Summary: Osteoporosis and Soft Tissue (Muscle and Fat) Disorders.

Journal Article J Am Geriatr Soc · January 2020 This report summarizes the presentations and recommendations of the eleventh annual American Geriatrics Society and National Institute on Aging research conference, "Osteoporosis and Soft Tissue (Muscle/Fat) Disorders," on March 11-12, 2019, in Bethesda, M ... Full text Link to item Cite

Lowering circulating apolipoprotein E levels improves aged bone fracture healing.

Journal Article JCI Insight · September 19, 2019 Age is a well-established risk factor for impaired bone fracture healing. Here, we identify a role for apolipoprotein E (ApoE) in age-associated impairment of bone fracture healing and osteoblast differentiation, and we investigate the mechanism by which A ... Full text Link to item Cite

Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration.

Journal Article Cells · February 20, 2019 Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of s ... Full text Link to item Cite

Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy.

Journal Article Frontiers in cell and developmental biology · January 2019 Our understanding of the molecular basis of aging has greatly increased over the past few decades. In this review, we provide an overview of the key signaling pathways associated with aging, and whose modulation has been shown to extend lifespan in a range ... Full text Cite

Thyroid Hormone Status Regulates Skeletal Muscle Response to Chronic Motor Nerve Stimulation.

Journal Article Front Physiol · 2019 Although both exercise and thyroid hormone (TH) status can cause cellular and metabolic changes in skeletal muscle, the impact of TH status on exercise-associated changes is not well understood. Here, we examined the effects of TH status on muscle fiber ty ... Full text Link to item Cite

Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.

Journal Article Nat Commun · December 5, 2018 The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that young macrophage cells produce factors that promote ost ... Full text Open Access Link to item Cite

The AMPK/p27Kip1 Axis Regulates Autophagy/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells.

Journal Article Stem Cell Reports · August 14, 2018 Skeletal muscle stem cell (MuSC) function declines with age and contributes to impaired muscle regeneration in older individuals. Acting through AMPK/p27Kip1, we have identified a pathway regulating the balance between autophagy, apoptosis, and senescence ... Full text Link to item Cite

Noncanonical agonist PPARγ ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy.

Journal Article Proc Natl Acad Sci U S A · January 16, 2018 The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ... Full text Link to item Cite

IL-6, cancer and cachexia: Metabolic dysfunction creates the perfect storm

Journal Article Translational Cancer Research · March 1, 2017 Full text Cite

Control of Skeletal Muscle Cell Growth and Size Through Adhesion GPCRs.

Chapter · 2016 Skeletal muscle homeostasis is regulated by a constant influx of chemicals and exposure to mechanical stimuli. A number of key signaling pathways that translate these stimuli into changes in muscle physiology have been established. The GPCR family known as ... Full text Link to item Cite

New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors.

Journal Article Ann N Y Acad Sci · December 2014 The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence o ... Full text Link to item Cite

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

Journal Article Proc Natl Acad Sci U S A · November 4, 2014 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56 ... Full text Link to item Cite

Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.

Journal Article Nature · September 4, 2014 Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One k ... Full text Link to item Cite

Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.

Journal Article Cell · June 5, 2014 Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metr ... Full text Link to item Cite

Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging.

Journal Article Cell · December 19, 2013 Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial ... Full text Link to item Cite

Characterization of the male Apc^Min/+ mouse as a hypogonadism model related to cancer cachexia

Journal Article Biology Open · December 15, 2013 Cancer cachexia, the unintentional loss of lean body mass, is associated with decreased quality of life and poor patient survival. Hypogonadism, involving a reduction in circulating testosterone, is associated with the cachectic condition. At this time the ... Full text Cite

Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.

Journal Article Cell Metab · November 5, 2013 Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that F ... Full text Link to item Cite

Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK.

Journal Article Am J Physiol Endocrinol Metab · May 15, 2013 Although catabolic signaling has a well-established role in muscle wasting during cancer cachexia, the suppression of anabolic signaling also warrants further investigation. In cachectic tumor-bearing mice, circulating IL-6 levels are associated with suppr ... Full text Link to item Cite

Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle.

Journal Article Molecular and cellular endocrinology · January 2013 Low endogenous testosterone production, known as hypogonadism is commonly associated with conditions inducing muscle wasting. Akt signaling can control skeletal muscle mass through mTOR regulation of protein synthesis and FoxO regulation of protein degrada ... Full text Cite

A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.

Journal Article Cell · December 7, 2012 PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results fro ... Full text Link to item Cite

Six1 and Six1 cofactor expression is altered during early skeletal muscle overload in mice.

Journal Article J Physiol Sci · September 2012 Six1 is a transcription factor that, along with cofactors (Eya1, Eya3, and Dach2), regulates skeletal muscle fiber-type and development. SIX1 (human) gene expression decreases after overload, but the time course of Six1 expression, if protein is affected, ... Full text Link to item Cite

IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the Apc^Min/+ mouse

Journal Article Skeletal Muscle · July 6, 2012 Background: Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of prote ... Full text Cite

The effect of exercise on IL-6-induced cachexia in the Apc^Min/+ mouse

Journal Article Journal of Cachexia, Sarcopenia and Muscle · January 1, 2012 Background Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the ApcMin/+ mouse, but does not induce wa ... Full text Cite

Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia.

Journal Article Biochimica et biophysica acta · December 2011 BackgroundThe Apc(Min/+) mouse, an animal model of colorectal cancer and cachexia, has a heterologous mutation in the Apc tumor suppressor gene, predisposing the mouse to intestinal and colon tumor development. This mouse develops intestinal polyp ... Full text Cite

Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

Journal Article Acta physiologica (Oxford, England) · August 2011 AimSkeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response ... Full text Cite

Muscle oxidative capacity during IL-6-dependent cancer cachexia.

Journal Article Am J Physiol Regul Integr Comp Physiol · February 2011 Many diseases are associated with catabolic conditions that induce skeletal muscle wasting. These various catabolic states may have similar and distinct mechanisms for inducing muscle protein loss. Mechanisms related to muscle wasting may also be related t ... Full text Link to item Cite

Branched-chain amino acid supplementation lowers perceived exertion but does not affect performance in untrained males.

Journal Article J Strength Cond Res · February 2011 The purpose of this study was to determine whether branched-chain amino acid (BCAA) supplementation affects aerobic performance, ratings of perceived exertion (RPE), or substrate utilization as compared with an isocaloric, carbohydrate (CHO) beverage or a ... Full text Link to item Cite

The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+) mouse.

Journal Article PloS one · January 2011 Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, ... Full text Cite

Activity level, apoptosis, and development of cachexia in Apc(Min/+) mice.

Journal Article J Appl Physiol (1985) · October 2010 Criteria for diagnosing cachexia in adults include unintentional loss in body weight, decreased strength, fatigue, anorexia, and low muscle mass. Cachexia is also associated with systemic inflammation, altered metabolism, and anemia. The Apc(Min/+) mouse i ... Full text Link to item Cite

Overload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6.

Journal Article Acta physiologica (Oxford, England) · December 2009 AimOverloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression ... Full text Cite

Effect of nandrolone decanoate administration on recovery from bupivacaine-induced muscle injury.

Journal Article Journal of applied physiology (Bethesda, Md. : 1985) · November 2009 Although testosterone administration elicits well-documented anabolic effects on skeletal muscle mass, the enhancement of muscle regeneration after injury has not been widely examined. The purpose of this study was to determine whether anabolic steroid adm ... Full text Cite

Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc ( Min/+ ) mouse.

Journal Article Pflugers Arch · March 2009 Interleukin-6 (IL-6) is necessary for cachexia in Apc ( Min/+ ) mice, but the mechanisms inducing this myofiber wasting have not been established. The purpose of this study was to examine gastrocnemius muscle wasting in the Apc ( Min/+ ) mouse and to deter ... Full text Link to item Cite

Effect of carbohydrate-protein supplement timing on acute exercise-induced muscle damage

Journal Article Journal of the International Society of Sports Nutrition · February 19, 2008 Purpose: To determine if timing of a supplement would have an effect on muscle damage, function and soreness. Methods: Twenty-seven untrained men (21 ± 3 yrs) were given a supplement before or after exercise. Subjects were randomly assigned to a pre exerci ... Full text Cite

Branched-chain amino acid supplementation and indicators of muscle damage after endurance exercise.

Journal Article International journal of sport nutrition and exercise metabolism · December 2007 The purpose of this study was to determine whether branched-chain amino acid (BCAA) supplementation attenuates indirect indicators of muscle damage during endurance exercise as compared with an isocaloric, carbohydrate (CHO) beverage or a noncaloric placeb ... Full text Cite