Investigating CD38 and NAD in Aging
Of late, there has been a growing interest in exploring mechanisms related to nicotinamide adenine dinucleotide (NAD) and the way in which their operation changes over the course of aging. This research has grown out of the last decade of attempts to produce calorie restriction mimetic drugs that might modestly slow aging, lengthy efforts that have resulted in a better understanding of some aspects of metabolism, but few leads to drug candidates. NAD is important in mitochondrial function, and many methods of slowing aging in laboratory species - calorie restriction included - involve changes in this part of cellular biochemistry. Increased levels of NAD in mice appear to produce better mitochondrial function and greater cellular housekeeping efforts, the second of which is fairly common among interventions that influence mitochondrial biochemistry. The flux of reactive oxygen species produced by mitochondria in the course of generating energy store molecules for the cell is used as one of many intracellular signals, and produces the housekeeping reaction when it grows larger.
Researchers have identified the enzyme, called CD38, that is responsible for the decrease in nicotinamide adenine dinucleotide (NAD) during aging, a process that is associated with age-related metabolic decline. Results demonstrated an increase in the presence of CD38 with aging in both mice and humans. "Previous studies have shown that levels of NAD decline during the aging process in several organisms. This decrease in NAD appears to be, at least in part, responsible for age-related metabolic decline." Researchers have shown that CD38, an enzyme that is present in inflammatory cells, is directly involved in the process that mediates the age-related NAD decline. Comparing 3- to 32-month-old mice, researchers found that levels of CD38 increased at least two to three times during chronological aging in all tissues tested, including the liver, fat, spleen and skeletal muscle.
To determine if the increase in CD38 observed in mice was also present in humans, researchers compared the levels in groups of individuals who were approximately 34-years-old to groups of individuals who were approximately 61-years-old. Similar to their observations in mice, researchers found that CD38 increased up to two-and-a-half times in the fat tissue of older individuals. "The future of our research will be to develop compounds that can inhibit the function of CD38 to increase NAD levels during aging. We are also investigating the mechanisms that lead to the increase in CD38 during the aging process."
I suppose this suggests that one way in which removing senescent cells benefits mice is that it reduces inflammation, reducing CD38 expression, helping to keep NAD+ levels normal...
I understand resveratrol and apiginin in apple skins inhibit CD38.