TY - JOUR
T1 - Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis
T2 - insights into neurovascular coupling and the impact of young blood factors
AU - Gulej, Rafal
AU - Nyúl-Tóth, Ádám
AU - Csik, Boglarka
AU - Petersen, Benjamin
AU - Faakye, Janet
AU - Negri, Sharon
AU - Chandragiri, Siva Sai
AU - Mukli, Peter
AU - Yabluchanskiy, Andriy
AU - Conley, Shannon
AU - Huffman, Derek M.
AU - Csiszar, Anna
AU - Tarantini, Stefano
AU - Ungvari, Zoltan
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to American Aging Association.
PY - 2024/2
Y1 - 2024/2
N2 - Age-related impairment of neurovascular coupling (NVC; “functional hyperemia”) is a critical factor in the development of vascular cognitive impairment (VCI). Recent geroscience research indicates that cell-autonomous mechanisms alone cannot explain all aspects of neurovascular aging. Circulating factors derived from other organs, including pro-geronic factors (increased with age and detrimental to vascular homeostasis) and anti-geronic factors (preventing cellular aging phenotypes and declining with age), are thought to orchestrate cellular aging processes. This study aimed to investigate the influence of age-related changes in circulating factors on neurovascular aging. Heterochronic parabiosis was utilized to assess how exposure to young or old systemic environments could modulate neurovascular aging. Results demonstrated a significant decline in NVC responses in aged mice subjected to isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis) when compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, exposure to young blood from parabionts significantly improved NVC in aged heterochronic parabionts [A-(Y)]. Conversely, young mice exposed to old blood from aged parabionts exhibited impaired NVC responses [Y-(A)]. In conclusion, even a brief exposure to a youthful humoral environment can mitigate neurovascular aging phenotypes, rejuvenating NVC responses. Conversely, short-term exposure to an aged humoral milieu in young mice accelerates the acquisition of neurovascular aging traits. These findings highlight the plasticity of neurovascular aging and suggest the presence of circulating anti-geronic factors capable of rejuvenating the aging cerebral microcirculation. Further research is needed to explore whether young blood factors can extend their rejuvenating effects to address other age-related cerebromicrovascular pathologies, such as blood–brain barrier integrity.
AB - Age-related impairment of neurovascular coupling (NVC; “functional hyperemia”) is a critical factor in the development of vascular cognitive impairment (VCI). Recent geroscience research indicates that cell-autonomous mechanisms alone cannot explain all aspects of neurovascular aging. Circulating factors derived from other organs, including pro-geronic factors (increased with age and detrimental to vascular homeostasis) and anti-geronic factors (preventing cellular aging phenotypes and declining with age), are thought to orchestrate cellular aging processes. This study aimed to investigate the influence of age-related changes in circulating factors on neurovascular aging. Heterochronic parabiosis was utilized to assess how exposure to young or old systemic environments could modulate neurovascular aging. Results demonstrated a significant decline in NVC responses in aged mice subjected to isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis) when compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, exposure to young blood from parabionts significantly improved NVC in aged heterochronic parabionts [A-(Y)]. Conversely, young mice exposed to old blood from aged parabionts exhibited impaired NVC responses [Y-(A)]. In conclusion, even a brief exposure to a youthful humoral environment can mitigate neurovascular aging phenotypes, rejuvenating NVC responses. Conversely, short-term exposure to an aged humoral milieu in young mice accelerates the acquisition of neurovascular aging traits. These findings highlight the plasticity of neurovascular aging and suggest the presence of circulating anti-geronic factors capable of rejuvenating the aging cerebral microcirculation. Further research is needed to explore whether young blood factors can extend their rejuvenating effects to address other age-related cerebromicrovascular pathologies, such as blood–brain barrier integrity.
KW - Ageing
KW - Cerebral microcirculation
KW - Cognitive health
KW - Endothelial dysfunction
KW - Heterochronic parabiosis
KW - Mouse brain
KW - Neurovascular coupling
KW - Reactive hyperemia
KW - Rejuvenation
UR - http://www.scopus.com/inward/record.url?scp=85180221076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180221076&partnerID=8YFLogxK
U2 - 10.1007/s11357-023-01039-2
DO - 10.1007/s11357-023-01039-2
M3 - Article
AN - SCOPUS:85180221076
SN - 2509-2715
VL - 46
SP - 327
EP - 347
JO - GeroScience
JF - GeroScience
IS - 1
ER -