Recent research has highlighted the importance of mitochondrial health in the context of ageing and longevity. This article explores the relationship between mitochondrial function, cellular health, and lifespan, emphasising strategies to enhance mitochondrial health for improved longevity.

Beyond energy production, these organelles play a vital role in regulating metabolic processes, apoptosis, and cellular signals. As ageing progresses, mitochondrial function typically declines, contributing to the ageing process and the onset of age-related diseases. Understanding how to promote mitochondrial health can be crucial for extending a healthy lifespan.

Mitochondrial dysfunction and ageing

Mitochondrial dysfunction is characterised by a decline in ATP production, increased production of reactive oxygen species (ROS), and impaired apoptosis signalling pathways. Studies have shown that age-related mitochondrial dysfunction leads to decreased muscle mass, reduced cognitive function, and increased susceptibility to metabolic diseases [1]. The accumulation of mitochondrial DNA (mtDNA) mutations, exacerbated by oxidative stress, is a hallmark of ageing [2].

Mechanisms linking mitochondria and longevity

1. Mitochondrial biogenesis

The process of mitochondrial biogenesis is critical for maintaining cellular energy homeostasis. PGC-1α is a key regulator of this process, stimulating the production of new mitochondria in response to energy stressors. Enhancing mitochondrial biogenesis has been linked to increased longevity in animal models [3].

2. Oxidative stress and antioxidant defence

Mitochondria are major sites of ROS production, which can damage cellular components and contribute to ageing. Organisms with enhanced antioxidant defences, such as superoxide dismutase and glutathione, display extended lifespans [4]. The balance between ROS production and antioxidant capacity is crucial for maintaining mitochondrial integrity.

3. NAD+ and metabolic regulation

NAD+ is a coenzyme involved in various metabolic pathways, including those associated with mitochondrial function. Ageing is often associated with decreased NAD+ levels. Supplementation with NAD+ precursors has been shown to restore mitochondrial function and enhance lifespan in preclinical models [5].

4. Caloric restriction and mitochondrial function

Caloric restriction (CR) is one of the most effective methods for extending lifespan across multiple species. CR enhances mitochondrial function and promotes mitochondrial biogenesis through various signalling pathways [6]. The effects of CR mimic those of exercise, another potent promoter of mitochondrial health.

5. Autophagy and mitochondrial quality control

Autophagy is a cellular process that removes dysfunctional mitochondria and degraded proteins. Dysfunctional autophagy is linked to age-related diseases, and enhancing autophagic processes has been shown to improve mitochondrial function and longevity [7].

Lifestyle interventions to enhance mitochondrial health

1. Physical exercise: Regular physical activity stimulates mitochondrial biogenesis and improves mitochondrial function [8]. Exercise promotes the expression of PGC-1α, leading to enhanced energy metabolism.
2. Dietary interventions: Nutrient-dense diets rich in antioxidants, such as fruits and vegetables, can combat oxidative stress [9]. Omega-3 fatty acids have also been associated with improved mitochondrial function.
3. Pharmacological agents: Compounds such as resveratrol, metformin, and rapamycin have been researched for their potential to enhance mitochondrial function and promote longevity [10][11]. These agents exhibit pleiotropic effects, such as reducing oxidative stress and enhancing autophagy.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Partha Ghosh, BNYS, MD(YS), is a general physician and a medical writer from Siliguri, Darjeeling.