Molecular and cellular pathways contributing to brain aging

Abstract

Aging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats

“…In the central nervous system, aging is associated with altered structure and connectivity, which leads to a decline in normal function. The decreases in neuron numbers and brain function during aging may be a determinant factor in the morphological and functional changes observed in neurodegenerative diseases [1][2][3][4][5]. These changes are accompanied by the deterioration of motor coordination and cognition in normal aging, which is worsened in age-associated neurodegenerative disorders such as AD [7][8][9][10][11].…”

“…Aging is a progressive, complex process accompanied with morphological, functional, and metabolic alterations in the brain, and a critical risk factor involved in the escalating prevalence of neurodegenerative, age-related diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD) [1][2][3][4][5]. A distinction can be made between the gradual decline in the structural and functional brain status in the non-diseased stage (primary or normal aging) and the progressive structural and functional loss resulting from age-related diseases (secondary aging) [6].…”

“…The levels of neurotrophic factors, such as brainderived neurotrophic factor (BDNF) and nerve growth factor (NGF), are also remarkably decreased in aging and AD, which can be linked to cognitive impairments [20][21][22]. In addition, it is well-established that aging is associated with declines in neurotransmitter and receptor levels, reduced synapse numbers, and increased oxidative stress, leading to the marked neurodegenerative status associated with age-related diseases [5,6,[23][24][25][26].…”

“…Most studies evaluating the efficacy of stem cells have been conducted in preclinical animal models or in patients with AD and PD, in which structural and functional brain capacities are extensively deteriorated. It could be postulated that early intervention to encounter the neuropathological alterations during primary aging would prevent or at least slow down the pathological processes leading to secondary aging, and hence reduce the incidence of age-related diseases [5,6,25,27,43,44]. Notably, studies investigating the administration of human (h)MSCs derived from bone marrow or adipose tissue in mouse models of hind limb ischemia have reported controversial outcomes regarding which type of MSCs is the most effective [45,46].…”

Improving Mental Health through Physical Activity: A Narrative Literature Review

“…Chronic adaptations to physical activity include increased basal levels of growth factors, cerebral blood perfusion, and cerebral angiogenesis (Zia et al, 2021). Heightened blood lactate accumulation, which occurs during intense exercise or intensity of exercise to which one is unaccustomed, is speculated to stimulate angiogenesis that is mediated by hydroxycarboxylic acid receptor 1 (HCAR1) (Morland et al, 2017).…”