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What they found (summary): NAD+ levels decline linearly with age in all tissues Sirtuins are glucose sensors , activated during caloric restriction and fasting The decline in NAD+ leads to pseudohypoxia in aging cells Supplementation with NAD+ precursors in animal models restores sirtuin activity Therapeutic perspectives: NMN, NR, sirtuin activators, CD38 inhibitors Why it matters: This is the reference article for the entire field

Similarly, Yan et al

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Third, while bulk proteomics provides a comprehensive view of cellular differentiation pattern, more precise methods such as single-cell technologies (transcriptomics or proteomics) 38,39 and spatiotemporal single-cell tracking 40,41 would further elucidate the detailed cellular composition and 3D organization during iHLO development

Aging involves DNA damage, mitochondrial decline, hormonal shifts, and cellular senescence all at once