Boosting NAD+ levels slows aging in cells from Werner syndrome patients

“Our results indicated compromised NAD+ metabolism in WS while NAD+ augmentation decreased senescence in both WS mesenchymal stem cells (MSCs) and primary fibroblasts, shedding light on potential therapeutics.”

BUFFALO, NY — May 1, 2025 — A new research paper was published in Aging (Aging-US) on April 2, 2025, as the cover of Volume 17, Issue 4, titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation.”

In this study, the team led by first author Sofie Lautrup and corresponding author Evandro F. Fang, from the University of Oslo and Akershus University Hospital in Norway, discovered that cells from people with Werner syndrome (WS)—a rare genetic disorder that causes  premature aging—have low levels of a molecule called NAD+ in their mitochondria. This molecule is essential for energy production, cellular metabolism, and maintaining cell health. The researchers also found a potential way to improve cell function in WS patients, pointing to new directions for treating age-related decline and other premature aging disorders.

Werner syndrome leads to signs of aging much earlier than normal, including problems such as cataracts, hair loss, and atherosclerosis by age 20 to 30. The team found that when the WRN gene is missing or damaged, cells cannot maintain healthy NAD+ levels in their mitochondria. As a result, the cells age more quickly and stop growing properly. When the researchers boosted NAD+ levels using nicotinamide riboside (a vitamin B3 compound) the affected stem cells and skin cells from patients showed less aging and improved mitochondrial activity.

“Interestingly, only 24 h treatment with 1 mM nicotinamide riboside (NR), an NAD+ precursor, rescued multiple pathways in the WRN−/− cells, including increased expression of genes driving mitochondrial and metabolism-related pathways, as well as proliferation-related pathways.”

The study also found that the WRN gene helps regulate other important genes that control how NAD+ is made in the body. Without WRN, this system becomes unbalanced, which affects how cells function, grow, and respond to stress. Although adding more NAD+ helped some cells look healthier, it could not completely fix the growth problems in other types of lab-grown cells. This suggests that while NAD+ supplementation is beneficial, it cannot fully replace the essential functions of the WRN gene.

These findings offer new insights into the biological mechanisms of aging and reinforce the therapeutic potential of targeting NAD+ metabolism in age-related and genetic diseases. Future studies will aim to better understand how subcellular NAD+ regulation interacts with mutations like those seen in WS. Finally, this research supports ongoing efforts to develop NAD+-based treatments that could slow cellular aging and improve quality of life for patients with premature aging conditions.

Read the full paper: DOI: https://doi.org/10.18632/aging.206236

Corresponding author: Evandro F. Fang – e.f.fang@medisin.uio.no

Keywords: aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation

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