Targeting Mitochondria to Control Ageing and Senescence

Abstract

Ageing is accompanied by a progressive impairment of cellular function and a systemic deterioration of tissues and organs, resulting in increased vulnerability to multiple diseases. Here, we review the interplay between two hallmarks of ageing, namely, mitochondrial dysfunction and cellular senescence. The targeting of specific mitochondrial features in senescent cells has the potential of delaying or even reverting the ageing process. A deeper and more comprehensive understanding of mitochondrial biology in senescent cells is necessary to effectively face this challenge. Here, we discuss the main alterations in mitochondrial functions and structure in both ageing and cellular senescence, highlighting the differences and similarities between the two processes. Moreover, we describe the treatments available to target these pathways and speculate on possible future directions of anti-ageing and anti-senescence therapies targeting mitochondria.

Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo

“…Mitochondrial dysfunction is a major contributor to aging [112][113][114], and melatonin has previously been reported to improve mitochondrial function on multiple levels in various cells and systems [107,[115][116][117]. In line with this, 200 µM melatonin increased TFAM and VDAC/Porin protein expression levels in aged human skin.…”

Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence

“…While mitochondrial turnover decreases in senescent cells, increased mitochondrial biogenesis leads to enhanced respiratory activity and ROS production [83]. The induced oxidative stress leads to cell damage, cell-cycle arrest, and senescence [84][85][86]. Senescent adipose mitochondrial dysfunction is an essential trigger of the induction of the complete senescent phenotype, including a proinflammatory SAPS [87][88][89].…”

Mitochondria: between aging, frailty and sarcopenia

“…This treatment has been tested on animal models with compelling results in the immediate time but with a loss of efficacy within a month, thus suggesting a potential benefit for acute rather than chronic condition ( Figure 1 ). Further future researches, optimization and technology advances are required to make this treatment effective and therefore useful in age-related diseases [ 7 ]. To conclude, even if considerable effort is still certainly required to face the frailty syndrome, mitochondria may potentially offer an important point of departure for its management.…”