Hormesis is any process in a cell or organism that exhibits a biphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, there is generally a favorable biological response to low exposures to toxins and other stressors. Hormesis comes from Greek hórmēsis “rapid motion, eagerness”, itself from ancient Greek hormáein “to set in motion, impel, urge on”. Hormetics is the term proposed for the study and science of hormesis.
Since the basic survival capacity of any biological system depends on its homeostatic ability, biogerontologists proposed that exposing cells and organisms to mild stress should result in the adaptive or hormetic response with various biological benefits. This idea has now gathered a large body of supportive evidence showing that repetitive mild stress exposure has anti-aging effects. Exercise is a paradigm for hormesis in this respect.
Some of the mild stresses used for such studies on the application of hormesis in aging research and interventions are heat shock, irradiation, prooxidants, hypergravity, and food restriction.
Some other natural and synthetic molecules, such as celastrols from medicinal herbs and curcumin from the spice turmeric have also been found to have hormetic beneficial effects. Such compounds which bring about their health beneficial effects by stimulating or by modulating stress response pathways in cells have been termed “hormetins”. Hormetic interventions have also been proposed at the clinical level, with a variety of stimuli, challenges and stressful actions, that aim to increase the dynamical complexity of the biological systems in humans.
This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer’s disease (AD).
Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham).
PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P < .0001; 100% less decline) scales.
This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.
Judith Campisi PhD
Judith Campisi received a PhD in biochemistry from the State University of New York at Stony Brook and completed her postdoctoral training in cell cycle regulation at the Dana-Farber Cancer Institute and Harvard Medical School. As an assistant and associate professor at the Boston University Medical School, she studied the role of cellular senescence in suppressing cancer and soon became convinced that senescent cells also contributed to aging. She joined the Lawrence Berkeley National Laboratory as a senior scientist in 1991.
In 2002, she started a second laboratory at the Buck Institute for Research on Aging. At both institutions, Dr Campisi established a broad program to understand the relationship between aging and age-related disease, with an emphasis on the interface between cancer and aging.
Dr Campisi has received numerous awards for her research, including two MERIT awards from the National Institute on Aging and awards from the AlliedSignal Corporation, Gerontological Society of America, and American Federation for Aging Research. She is a recipient of the Longevity prize from the IPSEN Foundation, the Bennett Cohen award from the University of Michigan, and the Schober award from Halle University, and she is the first recipient of the international Olav Thon Foundation prize in Natural Sciences and Medicine.
Dr Campisi currently serves on advisory committees for the Alliance for Aging Research, Progeria Research Foundation, and NIA’s Intervention Testing Program.