What this means
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite that regulates diverse cellular metabolic processes. Primary cilia, hair-like organelles on the cell surface, function as critical signaling hubs.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Animals or cells
- Kind of research
- Research in animals or cells
The science
- Original title
- A Cilia-Centered Nicotinamide Adenine Dinucleotide (NAD+) Signaling Network Regulates Hypothalamic Lysosomal Homeostasis and Metabolic Aging.
- Authors
- Park SE, Roh E, Park JW et al.
- Journal
- Aging cell
- Published
- Oct 22, 2026
- Study type
- Lab or animal study · indexed as animal research
- PMID
- 42902820 ↗
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite that regulates diverse cellular metabolic processes. Primary cilia, hair-like organelles on the cell surface, function as critical signaling hubs. Here, we demonstrate that cellular NAD+ levels are key regulators of both primary cilia growth and lysosomal function in hypothalamic neurons. NAD+ depletion induces ciliary shortening and diminishes lysosomal activity in a cilia-dependent manner. Mechanistically, the lysosomal repair complex protein CHMP4B translocates from periciliary satellites to lysosomes during lysosomal stress, a process impaired by ciliary dysgenesis. Disrupted lysosomal recruitment of CHMP4B leads to abnormal lysosomal Ca2+ signaling and lysosomal dysfunction. Aged mice with hypothalamic NAD+ deficiency exhibit shortened cilia and lysosomal stress phenotypes, both of which are restored by calorie restriction (CR). Moreover, CR improves aging-associated metabolic dysfunction, at least in part, through hypothalamic cilia-dependent mechanisms. These findings identify a primary cilium-mediated-NAD+ signaling axis that maintains lysosomal homeostasis in hypothalamic neurons, the disruption of which drives metabolic aging.
Park SE, Roh E, Park JW et al. A Cilia-Centered Nicotinamide Adenine Dinucleotide (NAD+) Signaling Network Regulates Hypothalamic Lysosomal Homeostasis and Metabolic Aging. Aging cell. 2026. doi:10.1111/acel.70745. PMID: 42902820. https://pubmed.ncbi.nlm.nih.gov/42902820/
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