Abstract
Life expectancy of humans has increased continuously up to the present days, but their health status (healthspan) was not enhanced by similar extent. To decrease enormous medical, economical and psychological burden that arise from this discrepancy, improvement of healthspan is needed that leads to delaying both aging processes and development of age-related diseases, thereby extending lifespan. Thus, development of new therapeutic tools to alleviate aging processes and related diseases and to increase life expectancy is a topic of increasing interest. It is widely accepted that ketosis (increased blood ketone body levels, e.g., β-hydroxybutyrate) can generate neuroprotective effects. Ketosis-evoked neuroprotective effects may lead to improvement in health status and delay both aging and the development of related diseases through improving mitochondrial function, antioxidant and anti-inflammatory effects, histone and non-histone acetylation, β-hydroxybutyrylation of histones, modulation of neurotransmitter systems and RNA functions. Administration of exogenous ketogenic supplements was proven to be an effective method to induce and maintain a healthy state of nutritional ketosis. Consequently, exogenous ketogenic supplements, such as ketone salts and ketone esters, may mitigate aging processes, delay the onset of age-associated diseases and extend lifespan through ketosis. The aim of this review is to summarize the main hallmarks of aging processes and certain signaling pathways in association with (putative) beneficial influences of exogenous ketogenic supplements-evoked ketosis on lifespan, aging processes, the most common age-related neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis), as well as impaired learning and memory functions.
Highlights
Aging processes result in irreversible decline of normal physiological functions and age-related diseases
This review discusses the hallmarks of aging and putative anti-aging molecular mechanisms by which EKSs may be able to exert their beneficial effects on lifespan, healthspan, aging, the most common age-related neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis), as well as learning and memory
Ketone bodies increase the expression of HCAR2 [278,279], and SIRTs (e.g., SIRT1 and SIRT3) and PGC1-α [164,278,280]. These results suggest that both βHB/HCAR2/AMPK/SIRT1/PGC1-α and βHB/HCAR2/AMPK/SIRT3/PGC1-α pathways can function in the CNS
Summary
Aging processes result in irreversible decline of normal physiological functions (timedependent functional decline) and age-related diseases. KEs, KSs and MCT oils can evoke anti-seizure and anti-epileptic effects [36,40,41,42], anxiolytic influence [26,43,44], regeneration of nervous system injuries [45] and alleviating effects on neurodegenerative diseases (such as Alzheimer’s disease) [41,46,47,48] These beneficial effects were induced likely through ketosis-evoked neuroprotective effects, for example, by improved mitochondrial functions, enhanced ATP levels, decreased inflammatory processes and decreased oxidative stress [23,24,34,49,50]. This review discusses the hallmarks of aging and putative anti-aging molecular mechanisms (pathways) by which EKSs may be able to exert their beneficial effects on lifespan, healthspan, aging, the most common age-related neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis), as well as learning and memory
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