José Antonio R. Piedrabuena -- The only drug for the brain and ageing

Ageing leads to functional changes in the hippocampus, a brain structure that is critical for learning, causing the ability to learn new tasks to decline with age. At the cellular level, synaptic contacts, synaptic strength and plasticity are reduced, hippocampal neurogenesis decreases with ageing, and imaging studies have shown hippocampal atrophy in older people.

These detrimental consequences of ageing can be prevented or reversed through exercise.. In fact, older adults who exercise throughout their lives have less brain tissue loss than sedentary individuals.

Lack of physical activity at any age is a major cause of obesity. Exercise not only helps to improve physical health, but also academic performance, as the positive effects of physical activity on cognition and brain function at molecular, cellular, systems and behavioural levels are evident. A growing number of studies support the idea that physical exercise is a lifestyle factor that could lead to a more effective immune system.

The decrease in neurogenesis in aged mice was reversed at 50% upon constant exercise. Furthermore, the good morphology of new neurons did not differ between young and old runners, indicating that the initial maturation of newborn neurons was not affected by ageing in those who are physically active.

Neuroinflammation and ageing go hand in hand and exercise has powerful anti-inflammatory effects.

Exercise, among other structures, affects the hippocampus, which plays a fundamental role in learning and in the formation and consolidation of memory, and is critically involved in the regulation of emotions, fear, anxiety and stress. It regulates and balances these via hormones and neurotrophic factors.

Exercise enhances and maintains synaptic plasticity, as well as potentiation and long-term depression (short- and long-term memory).

Neuroplasticity is the ability to adapt and reorganise to internal or external stimuli and occurs at the cellular, network and behavioural levels, reflected in the architecture of the intrinsic properties of hippocampal neurons and circuits.

Exercise increases the formation of new hippocampal neurons, necessary for new memory stores, as well as concentrations of neurotrophic factors and improved cognition. The possible circulating factors in the blood responsible for this effect were identified by plasma proteomics.

After exercise, we also have circulating anti-inflammatory myokines from skeletal muscle, and the liver and liver hepatokines are enhanced. The liver is an endocrine organ that emits its own factors, called hepatokines, as regulators of the metabolic and immune system and as I indicate, activated by exercise.

Likewise, we also lose fat because fat-derived adipokines are also activated. In recent years it has been recognised that adipose tissue secretes several bioactive molecules called adipokines or "adipocytokines", which are mainly derived from white adipose tissue (WAT) and play a major role in the homeostasis of several physiological processes, including food intake, regulation of energy balance, insulin action and glucose metabolism.

When we exercise we activate resistin, leptin and adiponectin, described by their function in my book on Mediterranean Diet and Physical Exercise. It is also involved in general vascular remodelling, blood pressure regulation and coagulation. For example, a sedentary lifestyle can lead to thrombosis and hypertension.

These factors may operate not only directly in the brain but also, as exemplified in the work of Horowitz et al. through extensive cross-talk between tissues. (""Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain". Alana M. Horowitz, Science,  10 Jul 2020).

In conclusion: exercise directly affects the brain and involves a large number of tissues. It is the only proven anti-ageing drug. Stress over time is a decisive factor in accelerating ageing. And we are in a situation of collective stress because of the pandemic and because of the disruptive messages of national institutional stability that a couple of political groupings, who believe that this will win elections, are in charge of. This indicates that our welfare is of no interest to them.

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