The intestinal short chain fatty acids (SCFAs) propionate and butyrate directly contribute to epigenetic regulation by supplying precursor molecules for histone lysine modifications. Nshanian et al. examine how propionate and butyrate supplementation affects gene regulation in colorectal cancer (CRC) cells, revealing distinct effects for each. Comparing normal cells with cancer cells shows context-dependent responses that might inform metabolic interventions.

Insights into how cholesterol-carrying low-density lipoproteins are structured, and how they interact with receptors to enter cells, could help to clarify the role of these particles in cardiovascular disease.

Cells regulate metabolic fluxes by changing enzyme levels according to their needs, but how do they regulate something that cannot be measured directly? In this issue of Nature Metabolism, Palme et al. address the fundamental question of how metabolic flux sensing is coupled to gene expression.

Nshanian et al. investigate the differential effects of the short-chain fatty acids propionate and butyrate on chromatin remodelling and gain insight into the mechanisms that drive selective histone acylation.

Kenny and Scharenberg et al. provide a broad overview of the fundamental aspects of choline metabolism and cellular handling, and how it impacts physiology and pathology.

The intestinal short chain fatty acids (SCFAs) propionate and butyrate directly contribute to epigenetic regulation by supplying precursor molecules for histone lysine modifications. Nshanian et al. examine how propionate and butyrate supplementation affects gene regulation in colorectal cancer (CRC) cells, revealing distinct effects for each. Comparing normal cells with cancer cells shows context-dependent responses that might inform metabolic interventions.

Insights into how cholesterol-carrying low-density lipoproteins are structured, and how they interact with receptors to enter cells, could help to clarify the role of these particles in cardiovascular disease.

Cells regulate metabolic fluxes by changing enzyme levels according to their needs, but how do they regulate something that cannot be measured directly? In this issue of Nature Metabolism, Palme et al. address the fundamental question of how metabolic flux sensing is coupled to gene expression.

Although the emerging field of geroscience holds great promise for identifying new approaches to improve healthspan, several risks of the current framework are underappreciated. Long time horizons, challenges in identifying causality-driven surrogate biomarkers of aging, and the potential for biological trade-offs and antagonistic effects across various timescales mean it will be hard to know when such interventions have a net benefit. We propose eight strategies to mitigate these risks going forwards.