Nicotinamide extends replicative lifespan of human cells

Area of Science:

• Cell Biology
• Gerontology
• Biochemistry

Background:

• Cellular senescence is a hallmark of aging.
• Reactive oxygen species (ROS) contribute to aging and cellular damage.
• Nicotinamide's role in aging is context-dependent, showing varied effects in different organisms.

Purpose of the Study:

• To investigate the effect of nicotinamide on human fibroblast aging.
• To determine if nicotinamide can extend cellular replicative lifespan.
• To elucidate the underlying mechanisms of nicotinamide's impact on cellular senescence.

Main Methods:

• Ongoing application of nicotinamide to normal human fibroblasts.
• Measurement of aging phenotype markers, replicative lifespan, and population doublings.
• Analysis of reactive oxygen species (ROS) levels, oxidative damage, telomere shortening, and key protein expressions (p53, p21WAF1, phospho-Rb).
• Assessment of cellular energy metabolism, including ATP levels, mitochondrial membrane potential, and respiration rates.

Main Results:

• Nicotinamide treatment attenuated the aging phenotype and increased fibroblast replicative lifespan by over 1.6-fold.
• Cells showed reduced ROS levels and oxidative damage, with decelerated telomere shortening.
• Key senescence-associated proteins (p53, p21WAF1, phospho-Rb) remained at levels similar to proliferating cells.
• Nicotinamide decreased ATP levels and cellular respiration while maintaining mitochondrial membrane potential, with lower superoxide anion levels.

Conclusions:

• Nicotinamide extends the lifespan of human fibroblasts, counteracting its pro-aging effects observed in yeast.
• The anti-aging effects in fibroblasts may be mediated by reduced mitochondrial activity and ROS production.
• Nicotinamide offers a potential therapeutic strategy for mitigating cellular aging in human cells.