Evidence is accruing that a cognitive-behavioral regimen integrating cognitive techniques (meditation-based anti-stress, anti-inflammatory techniques, others), dietary modification ("dietary restriction" or modified dietary restriction), and certain forms of aerobic exercise, may prolong the healthy life span in humans. Recent research has identified some of the likely molecular mediators of these potentially broad-ranging, health-enhancing and anti-aging effects; these include DHEA, interleukins -10 and -4 (IL-10, 1L-4), and especially melatonin. Relatedly, what some are calling a revolution in biology and medicine has been emerging from research on stem cells and regeneration processes more generally. Dogma regarding limitations on the regenerative capacities of adult vertebrates is being cautiously yet enthusiastically revised in the wake of rapidly accumulating discoveries of more types of adult stem cells in mammals, including humans. For example, a recent review by D. Krause of Yale concluded that "in the [adult] bone marrow, in addition to hematopoietic stem cells and supportive stromal cells, there are cells with the potential to differentiate into mature cells of the heart, liver, kidney, lungs, GI tract, skin, bone, muscle, cartilage, fat, endothelium and brain." In addition, very recent studies have shown that DHEA, ILs-10 and -4, and melatonin all possess potential regenerative, including stem cell-activating, properties. More than a quarter of a century ago, Walter Pierpaoli initiated a series of extraordinary studies that demonstrated in experimental animals the potential for dramatic regeneration associated with changes in the pineal gland and bone marrow. This appeared to be not only retardation of aging, but also its reversal. Furthermore, as Pierpaoli was attempting to understand both anti-aging regeneration and oncogenesis, he was focusing on both pro- and anti-mitotic mechanisms: recent research now suggests that there is a nonpathologic, "healthy" form of regeneration that is actually antagonistic to oncogenesis, and that melatonin may be important in this form of regeneration. This paper explores Pierpaoli's pioneering studies in light of recent developments in stem cell and regenerative biology, particularly as related to the regenerative potential associated with certain cognitive-behavioral practices, and includes evidence on this subject presented for the first time.