Studies of the various approaches to raising NAD+ levels in aged mitochondria are a good illustration of the importance of the loss of mitochondrial function in degenerative aging. Researchers have studied this effect in numerous tissues and organs, with most such work examining muscle or the brain, both energy-hungry tissues and thus more dependent on their mitochondria for normal function.
Today's open access paper is a study of mitochondrial function in a tissue that is less well studied in this context. The authors reporting that supplementation with nicotinamide mononucleotide (NMN) can restore lost fertility in old mice by improving mitochondrial function in oocytes.
Mitochondria are the power plants of the cell, responsible for packaging the chemical energy store molecule ATP that is used to power cellular operations. For reasons that remain poorly understood, meaning that they are not well connected to the underlying molecular damage of aging, mitochondria become dysfunctional throughout the body with advancing age. Mitochondria are the descendants of ancient symbiotic bacteria, and they normally divide and fuse like bacteria, as well as passing component parts of their molecular machinery from one to another. In cells in old tissues, these dynamics change in ways that make mitochondria resistant to the quality control processes responsible for clearing out damaged structures in the cell. Cells become populated by problematic, poorly functioning mitochondria, and suffer accordingly.
A reduced amount of NAD+, a utility molecule important to a number of processes in mitochondria, is one proximate cause of these issues. The pace of synthesis and recycling of NAD+ falls off due to lowered levels of precursors and other necessary ingredients for the chemical reactions involved. This might be traced back to altered levels of gene expression due to epigenetic changes characteristic of aging, but this is still an exploration of proximate causes, and says little about what the underlying root causes might be in any detail.
To the extent that providing more NAD+ to cells restores mitochondrial function and thus cellular function to some degree, and this outcome is well demonstrated in mice, these benefits may be largely the result of enabling sufficient clearance of worn mitochondria to improve overall ATP production. This is better maintenance rather than better function per se; other lines of research also suggest that quality control is the critical item in mitochondrial function. When it comes to the means of raising NAD+ levels, delivery of NAD+ itself is not very efficient, and most current approaches are thus focused on delivering precursor molecules used in the synthesis or recycling of NAD+. Of these only nicotinamide riboside has even early clinical data to show some form of benefit in aged humans, but that will likely change over the next few years as more groups publish their work.
Source: Fight Aging!