Biological aging processes underlying cognitive decline and neurodegenerative disease

Area of Science:

• Neuroscience
• Geroscience
• Gerontology

Background:

• Alzheimer's disease and related dementias (ADRD) are leading causes of disability and mortality in older adults.
• Aging is the primary risk factor for ADRD, with cognitive decline evident even in non-demented older individuals.
• Shared pathophysiological mechanisms may link normal aging to neurodegenerative processes.

Purpose of the Study:

• To review lifespan changes in cognition, brain structure, and protein accumulation in humans and animal models.
• To highlight aging processes dysregulated in neurodegenerative diseases.
• To link biological aging to ADRD pathogenesis and explore therapeutic avenues.

Main Methods:

• Review of human lifespan studies on cognition, brain morphology, and neuropathology.
• Integration of mechanistic evidence from animal models.
• Synthesis of clinical and translational research linking aging processes to ADRD.

Main Results:

• Significant changes in cognition, brain morphology, and protein accumulation occur across the lifespan.
• Aberrant autophagy, mitochondrial dysfunction, senescence, epigenetic alterations, cerebrovascular issues, inflammation, and lipid dysregulation are key aging processes implicated in ADRD.
• Biological aging processes are directly linked to the pathogenesis of ADRD.

Conclusions:

• Targeting fundamental biological aging processes presents a promising, underexplored therapeutic strategy for age-related cognitive decline and ADRD.
• Interdisciplinary collaboration between geroscience and neuroscience is crucial.
• Development of improved translational animal models is needed for therapeutic discovery.