Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases

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.

Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases

“…The accumulation of oxidative damage may stem from a combination of mitochondrial dysfunction leading to over production of reactive oxygen species coupled with reduced autophagy, resulting in reduced turnover of damaged lipids, proteins, and organelles. It has been postulated that caloric restriction reduces the amount of glucose available as a substrate and induces ketogenesis, which increases turnover of damaged macromolecules [61,62]. Our data suggest that in addition to these changes, caloric restriction may inhibit inflammation, which is consistent with the neuroprotective effects of caloric restriction observed in models for neurodegenerative diseases.…”

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

“… 19 The ketone bodies are also involved in multiple metabolic pathways, and protective effects of ketone bodies 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. 89 Thus, the accumulation of ketone bodies can at least partly explain the influence of the gut microbiota by KD, 20 which thereby inhibiting colitis, improving several diseases such as epilepsy. The summary of changes in metabolism and gut microbiota induced by the ketogenic diet is shown in Fig.…”

Mitochondrially-Targeted Therapeutic Strategies for Alzheimer’s Disease

“…Alternatively, by improving mitochondrial function, Ab production is decreased while the soluble APPa production is enhanced and this promotes neurite growth by binding to p75 receptor of BDNF [ 313 ]. In animal studies and clinical trials, KD induced stabilization of synaptic functions due to enhanced mitochondrial biogenesis [ 314 ], reduced ROS production, and enhanced cellular bioenergetics [ 315 ]. In rat cultured hippocampal neurons, KB protects against Ab toxicity [ 316 , 317 ].…”