Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System
Open accessAbstract
How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations.
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Many regenerative approaches that work well in young individuals often fail in older ones.
“Many regenerative approaches that work well in young individuals often fail in older ones25,26.”
From Reprogramming to recover youthful epigenetic information and restore vision (2020) · cites this paper as [25]
The Abstract and Discussion (page not provided) report that Pten deletion promotes axon regeneration in young mice but has a greatly diminished effect in older mice. The paper tests one approach in mice; it does not establish that many approaches often fail in older individuals, and it describes diminished regeneration rather than complete failure. (LLM, conf=0.85)
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- Authors
- Geoffroy, C. G., Hilton, B. J., Tetzlaff, W., & Zheng, B.
- Affiliations
- University of California San Diego (US)
- University of British Columbia (CA)
- Corresponding author
- Tetzlaff, Wolfram
- Zheng, Binhai
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 15
- Issue
- 2
- Pages
- 238-246
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5050004
- OpenAlex
- W2319017449
- Cited by
- 159
- References
- 41
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 17 · 2023: 15 · 2022: 16 · 2021: 25 · 2020: 17 · 2019: 18 · 2018: 11 · 2017: 9 · 2016: 6
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research
- National Institute on Aging (T32AG000216)
- National Institute of Neurological Disorders and Stroke (R01NS054734, P30NS047101, R01NS093055)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- axon regeneration, aging, central nervous system injury, PTEN deletion, corticospinal neurons, rubrospinal neurons, axotomy, neuronal soma size, astroglial activation, neuroinflammation, spinal cord injury, axonal repair
- MeSH terms
- Aging, Animals, Astrocytes, Axons, Central Nervous System, Inflammation, Mammals, Nerve Regeneration, Pyramidal Tracts, Spinal Cord Injuries, Signal Transduction, Biomarkers, Down-Regulation, Gene Deletion, Axotomy, PTEN Phosphohydrolase, Mice, TOR Serine-Threonine Kinases
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