| Autor: |
Gonzales MM; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases.; Department of Neurology., Garbarino VR; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases., Pollet E; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases., Palavicini JP; Barshop Institute for Longevity and Aging Studies, and.; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Kellogg DL Jr; Barshop Institute for Longevity and Aging Studies, and.; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Geriatric Research and Education Center, South Texas Veterans Health Care System, San Antonio, Texas, USA., Kraig E; Barshop Institute for Longevity and Aging Studies, and.; Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Orr ME; Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. |
| Abstrakt: |
Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability and mortality in later life. As with many chronic conditions, aging is the single most influential factor in the development of ADRD. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview of changes in cognition, brain morphology, and neuropathological protein accumulation across the lifespan in humans, with complementary and mechanistic evidence from animal models. Next, we highlight selected aging processes that are differentially regulated in neurodegenerative disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular dysfunction, inflammation, and lipid dysregulation. We summarize research across clinical and translational studies to link biological aging processes to underlying ADRD pathogenesis. Targeting fundamental processes underlying biological aging may represent a yet relatively unexplored avenue to attenuate both age-related cognitive decline and ADRD. Collaboration across the fields of geroscience and neuroscience, coupled with the development of new translational animal models that more closely align with human disease processes, is necessary to advance novel therapeutic discovery in this realm. |
