Ageing, neurodegeneration and brain rejuvenation

Abstract

Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.

Mitochondrial Aging Defects Emerge in Directly Reprogrammed Human Neurons due to Their Metabolic Profile

“…Interestingly, inherited mitochondrial diseases that can be caused by mutations in genes encoded on the nuclear DNA, which encodes the vast majority of mitochondrial genes, or in genes that are encoded in mtDNA are often associated with neurodegenerative phenotypes, indicating a particular vulnerability of brain neurons to mitochondrial defects (Simon and Johns, 1999). Similarly, the human brain is an organ that is strongly affected by aging, and advanced age is by far the strongest risk factor for most neurodegenerative disorders (Wyss-Coray, 2016). …”

Presenilins Interactome in Alzheimer’s Disease and Pathological Ageing

“…In this regard, the amyloid cascade is complemented with the abovelisted processes disturbed in AD. Similarly, pathological ageing is manifested by a loss of protein homeostasis, DNA damage, lysosomal dysfunction, epigenetic changes, immune deregulation, or disturbed calcium homeostasis [6]. Altogether, AD and PA might result from presenilin-dependent processes or presenilins' interactomes.…”

HEAVEN in the Making: Between the Rock (the Academe) and a Hard Case (a Head Transplant)

“…Studies from nine independent laboratories indicate that stem-cell activity is increased while other indices of aging are delayed or reversed in several tissues of aged mice that share a circulatory system with young mice (Castellano, Kirby, and Wyss-Coray 2015;WyssCoray 2016;Castellano et al 2017). These studies included initial observations of effects on muscle and the liver; reports of effects on the brain by four separate laboratories; and observations of rejuvenating effects in the pancreas, the heart, bone, and muscle (Castellano, Kirby, and WyssCoray 2015;Wyss-Coray 2016;Castellano et al 2017). In the same vein, postreproductive life expectancy extension is coupled with late (but not reproductive life) births (Falick Michaeli et al 2015a;Falick Michaeli et al 2015b), suggesting that the fetus releases substances that delay aging.…”