Key aspects of human cell aging reversed by new compounds

Key aspects of the ageing of human cells can be reversed by new compounds developed at the University of Exeter, research shows.

In a laboratory study of endothelial cells -- which line the inside of blood vessels -- researchers tested compounds designed to target mitochondria (the "power stations" of cells).
In the samples used in the study, the number of senescent cells (older cells that have deteriorated and stopped dividing) was reduced by up to 50%. The Exeter team also identified two splicing factors (a component of cells) that play a key role in when and how endothelial cells become senescent.
The findings raise the possibility of future treatments not only for blood vessels -- which become stiffer as they age, raising the risk of problems including heart attacks and strokes -- but also for other cells.
"As human bodies age, they accumulate old (senescent) cells that do not function as well as younger cells," said Professor Lorna Harries, of the University of Exeter Medical School.
"This is not just an effect of ageing -- it's a reason why we age.
"The compounds developed at Exeter have the potential to tweak the mechanisms by which this ageing of cells happens.
"We used to think age-related diseases like cancer, dementia and diabetes each had a unique cause, but they actually track back to one or two common mechanisms.
"This research focuses on one of these mechanisms, and the findings with our compounds have potentially opened up the way for new therapeutic approaches in the future.
"This may well be the basis for a new generation of anti-degenerative drugs."
Professor Harries said the goal was to help people stay healthier for longer. She added: "This is about health span and quality of life, rather than merely extending lifespan."
In a paper published last year, the team demonstrated a new way to rejuvenate old cells in the laboratory.
However, the new research looked at precisely targeting and rejuvenating mitochondria in old cells.
Each one of our genes is capable of making more than one product, and splicing factors are the genes that make the decision about which of these products are made.
In this new work, using novel chemicals, the researchers were able to very specifically target two splicing factors (SRSF2 or HNRNPD) that play a key role in determining how and why our cells change with advancing age.
"Nearly half of the aged cells we tested showed signs of rejuvenating into young cell models," said Professor Harries.
The researchers tested three different compounds, all developed at the University of Exeter, and found each produced a 40-50% drop in the number of senescent blood vessel cells.
The compounds in question -- AP39, AP123 and RT01 -- have been designed by the Exeter team to selectively deliver minute quantities of the gas hydrogen sulfide to the mitochondria in cells and help the old or damaged cells to generate the 'energy' needed for survival and to reduce senescence.
"Our compounds provide mitochondria in cells with an alternative fuel to help them function properly," said Professor Matt Whiteman, also from the University of Exeter.
"Many disease states can essentially be viewed as accelerated ageing, and keeping mitochondria healthy helps either prevent or, in many cases using animal models, reverse this.
"Our current study shows that splicing factors play a key role in determining how our compounds work."
The research was funded by Dunhill Medical Trust and the Medical Research Council.
 

Journal Reference:

1. Eva Latorre, Roberta Torregrossa, Mark E. Wood, Matthew Whiteman, Lorna W. Harries. Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging, 2018; DOI: 10.18632/aging.101500 

Courtesy: ScienceDaily
 

Mere expectation of checking work email after hours harms health of workers and families

Employer expectations of work email monitoring during nonwork hours are detrimental to the health and well-being of not only employees but their family members as well.

William Becker, a Virginia Tech associate professor of management in the Pamplin College of Business, co-authored a new study, "Killing me softly: electronic communications monitoring and employee and significant-other well-being," showing that such expectations result in anxiety, which adversely affects the health of employees and their families.
"The competing demands of work and nonwork lives present a dilemma for employees," Becker said, "which triggers feelings of anxiety and endangers work and personal lives."
Other studies have shown that the stress of increased job demands leads to strain and conflict in family relationships when the employee is unable to fulfill nonwork roles at home -- "such as when someone brings work home to finish up."
Their new study, he said, demonstrates that employees do not need to spend actual time on work in their off-hours to experience the harmful effects. The mere expectations of availability increase strain for employees and their significant others -- even when employees do not engage in actual work during nonwork time.
Unlike work-related demands that deplete employee resources, physical and psychological, by requiring time away from home, "the insidious impact of 'always on' organizational culture is often unaccounted for or disguised as a benefit -- increased convenience, for example, or higher autonomy and control over work-life boundaries," Becker said.
"Our research exposes the reality: 'flexible work boundaries' often turn into 'work without boundaries,' compromising an employee's and their family's health and well-being."
As negative health outcomes are costly to them, what can employers do to mitigate the adverse effects identified by the study? Becker said policies that reduce expectations to monitor electronic communication outside of work would be ideal.
When that is not an option, the solution may be to establish boundaries on when electronic communication is acceptable during off-hours by setting up off-hour email windows or schedules when employees are available to respond.
Additionally, he said, organizational expectations should be communicated clearly. "If the nature of a job requires email availability, such expectations should be stated formally as a part of job responsibilities." Knowing these expectations upfront may reduce anxiety in employees and increase understanding from their family members, he said.
As for employees, they could consider practicing mindfulness, which has been shown to be effective in reducing anxiety, Becker said. Mindfulness may help employees "be present" in family interactions, which could help reduce conflict and improve relationship satisfaction. And, he added, mindfulness is within the employee's control when email expectations are not.
Becker, whose research interests include work emotion, turnover, organizational neuroscience, and leadership, is based at Virginia Tech's National Capital Region campus in metro Washington, D.C.
His study, co-authored with Liuba Y. Belkin, of Lehigh University; Samantha A. Conroy, of Colorado State University; and Sarah Tuskey, a Virginia Tech Ph.D. student in executive business research, will be presented at the Academy of Management annual meeting in Chicago on August 10-14.
"Employees today must navigate more complex boundaries between work and family than ever before," said Becker. "Employer expectations during nonwork hours appear to increase this burden, as employees feel an obligation to shift roles throughout their nonwork time.
"Efforts to manage these expectations are more important than ever, given our findings that employees' families are also affected by these expectations."
 

Journal Reference:

1. William J. Becker, Liuba Belkin, Sarah Tuskey. Killing me softly: Electronic communications monitoring and employee and spouse well-being. Academy of Management Proceedings, 2018; 2018 (1): 12574 DOI: 10.5465/AMBPP.2018.121 

Courtesy: ScienceDaily