Insights into Neurogenesis and Aging: Potential Therapy for Degenerative Disease?

Robert A Marr; Rosanne M Thomas; Daniel A Peterson

Disclosures

Future Neurology. 2010;5(4):527-541. 

In This Article

Abstract and Introduction

Abstract

Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age.

Introduction

There are few therapeutic options for restoring neurologic function following brain injury or disease at present. Thus, there is broad appeal for the idea that stem cells could be used as therapeutic intervention for age-related cognitive decline and neurodegenerative disorders as successfully as hematopoietic stem cells are used for the treatment of leukemia. The incidence of age-related neurodegenerative disorders can be expected to increase, given that the number of adults over the age of 65 years is expected to increase to 20% of the US population by the year 2050.[1] As medical care continues to improve longevity, the achievement of successful aging will have tremendous individual and economic importance.

Aging, simply the act of living longer, is a major risk factor for the development of neurodegenerative disorders as illustrated by the median onset age for diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and others.[2–4] Although extensive research into the etiology of such diseases has yet to define a common causal factor, this inability to identify causality is congruent with the high variability of the aging process itself. If we define 'successful aging' as those older individuals who are able to function independently with intact cognitive capacity, then 'pathological aging' runs the spectrum from dementia to culturally expected forgetfulness with individuals exhibiting highly variable functional decline over a similar lifespan. Likewise, the onset and progression of neurodegenerative disorders is quite variable.

Although the existence of neurogenesis in the adult brain is now universally accepted by the scientific community, it has been a slow and often contentious process to refute the long-held dogma that no new neurons were generated in the adult brain. Additionally, elucidating details about the stages of neurogenesis and its functional significance, as well as the molecular processes guiding these events, was limited until recent technological advances allowed appropriate experimental investigation.[5] We have come incredibly far in the 40 years since adult neurogenesis was first suggested to a skeptical scientific community and it is apparent that we are ready for the next step: determining therapeutic management of this phenomenon. This review will examine the feasibility of successful use of neurogenesis through stem cell and gene therapies for the management of neurodegenerative disease and age-related cognitive decline.

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