From discoveries in ageing research to therapeutics for healthy ageing

Abstract

For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

“…Since functional mitochondria are essential for homeostasis and survival of the HF epithelium and HF stem cells (at least in mice in vivo), continuous stimulation of PPAR‐γ by endogenous ligands may be required for the maintenance of HF energy metabolism, for intrafollicular PPAR‐γ expression and activity would then play an important role in human HF physiology. Moreover, given the central role of accumulating mitochondrial defects in tissue ageing, pharmacological stimulation of intrafollicular PPAR‐γ signalling is a plausible candidate strategy for improving the mitochondrial energy metabolism of ageing or stressed HFs.…”

“…given the central role of accumulating mitochondrial defects in tissue ageing, [116][117][118] pharmacological stimulation of intrafollicular PPAR-γ signalling is a plausible candidate strategy for improving the mitochondrial energy metabolism of ageing or stressed HFs.…”

Maximum reproductive lifespan correlates with CD33rSIGLEC gene number: Implications for NADPH oxidase‐derived reactive oxygen species in aging

“…Since Harman first proposed that ROS are mediators of the aging process, much research has supported this concept. There are of course many mechanisms of aging, and ROS is only one contributor . In fact, it is well documented that ROS can be beneficial as well as detrimental, and it is the balance of ROS production that apparently matters (too much is bad, too little is bad).…”

“…Mitochondria are generally considered the primary source of ROS involved in aging . ROS produced by mitochondria are a byproduct of normal functioning of the electron transport chain and inhibitors of respiratory chain such as rotenone have been shown to suppress the ability of hormones and cytokines to produce ROS in various cell types .…”

“…Aging is a complex biological process varying widely between species, being influenced by numerous interacting factors. [1][2][3][4][5][6] Logically, aging also impacts maximum lifespan, a number that also varies widely between species. One contributor to aging appears to be reactive oxygen species (ROS), originating from two major sources: mitochondria (a relatively constant source in most cell types) 7 and from NADPH oxidase (NOX) enzymes.…”