title: What to look for beyond "pathogenic" factors in senile dementia? A functional deficiency of Ca²⁺ signaling.
abstract: We have contended that senile conditions--illnesses after age 60 and fully age-penetrating, such as tooth, hearing or memory loss--are not distinct "diseases" in medical nature, because they are caused by aging. Since the pace of aging varies among individuals and is much influenced by risk factors, senile conditions will only affect some but not all elderly. However, perhaps due to its unusually heavy burdens and tremendous social pressures, senile dementia (SD) has been singled out from other senile conditions and redefined as a curable "disease" (Alzheimer's). This highly popular definition has thus opened a Pandora's box that has been confusing us up until now and warrants further scrutiny. In this article we discuss: a) what should we logically look for in SD beyond "pathogenic" factors?; b) why Ca2+, a central regulator in neurotransmission, should be the primary player in SD; c) why the functionality of Ca2+ signaling, or its vibrant wave frequency and amplitude, must undergo down-regulation during aging, though this is intriguingly accompanied by an increase of Ca2+ "levels"; d) why intervention for SD should target Ca2+ function by promoting energy metabolisms and by Ca2+ agonists such as caffeine and nicotine, but not by "antagonists" as widely believed; and e) why our study should focus on aging, not "cell death", a seemingly attractive paradigm but perhaps too late for intervention. We also seek answers for why unproven hypotheses can become dogmas and inhibit self-correcting mechanisms of science.
authors.affiliation: Aging Research Laboratory, Bay Pines VA Healthcare System, Bay Pines, Florida, USA. ming.chen@va.gov
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Huey T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Sawmiller
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D020013:Calcium Signaling / Q000502:physiology*; D016923:Cell Death; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy / Q000209:etiology*; D012307:Risk Factors
chemical_list: D002121:Calcium Channel Blockers; D002118:Calcium