William Holland

Ceramides and other sphingolipids as drivers of cardiovascular disease

Nature Reviews Cardiology · 2021 · 377 citations

The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

Cell Metabolism · 2020 · 326 citations

Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age

Aging Cell · 2023 · 263 citations

Aging results in an elevated burden of senescent cells, senescence-associated secretory phenotype (SASP), and tissue infiltration of immune cells contributing to chronic low-grade inflammation and a host of age-related diseases. Recent evidence suggests that the clearance of senescent cells alleviates chronic inflammation and its associated dysfunction and diseases. However, the effect of this intervention on metabolic function in old age remains poorly understood. Here, we demonstrate that dasa…

Lysophospholipid acylation modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle

Journal of Clinical Investigation · 2021 · 76 citations

Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analysis of primary myocytes from individuals who were insulin-sensitive and lean (LN) or insulin-resistant with obesity (OB) revealed several species of lysophospholipids (lyso-PLs) that were differentially abundant. These changes coincided with greater expression of lysophosphatidylchol…

Disuse‐induced muscle fibrosis, cellular senescence, and senescence‐associated secretory phenotype in older adults are alleviated during re‐ambulation with metformin pre‐treatment

Aging Cell · 2023 · 52 citations

Muscle inflammation and fibrosis underlie disuse-related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling and poor muscle recovery after disuse. In rodents, metformin has been shown to prevent cellular senescence/senescent associated secretory phenotype (SASP), inflammation, and fibrosis making it a potentially practical therapeutic solution. Thus, the purpose of this study w…