Metabolism, is it true that it slows down with age?

Article by SoLongevity Research

The Metabolism

With age the metabolism becomes less efficient, but through caloric restriction we can act on molecular processes, slowing down aging and related diseases.Sooner or later they all go through it. After the age of 30, the metabolism – that is, all the chemical reactions that take place in a living organism – begins to slow down, so it is more difficult to keep your body shape, you put on fat, you lose muscle mass and so on.All this happens because, with age, those systems that have the task of capturing nutrients and maintaining their balance (homeostasis) become less efficient. In short, the metabolism no longer corresponds to the body’s energy demand.

With ageing, the metabolism no longer corresponds to the body’s energy demand.

Four metabolic pathways “losing balance”One of the metabolic pathways most prone to this dysregulation is insulin one, the hormone managing the glucose level within the blood, intercepting the sugar molecules to bring them to the cells, where they are converted into energy. Glucose, in fact, is the main source of energy of all organisms: a glucose molecule, by breaking down and oxidizing, can provide up to 32 molecules of adenosine triphosphate, or ATP, which is the “exchange currency” of energy in the cells.

Among the metabolic pathways most prone to dysregulation are those of insulin, mTOR, AMPK and sirtuins, the longevity proteins.

ATP molecules are the energy exchange currencies of organisms.Another metabolic pathway that loses its impact with advancing age is mTOR one, a protein that perceives the levels of amino acids, i.e. the building blocks that make up proteins, and regulates cell growth (the name mTOR stands for mammalian Target Of Rapamycin, i.e. Target of rapamycin in mammals).Then there is the metabolic pathway of AMPK, another enzyme that perceives both nutrients and energy molecules. The activation of AMPK leads to a metabolic rebalancing (characterized by inhibition of anabolic processes and stimulation of catabolic processes). The coordinated regulation of these processes, which triggers the increase in AMPK, therefore favours systems of maintenance, recycling of damaged molecules (a process called “proteostasis”) and repair of damage, increasing resistance to stress and promoting cell survival.Last, but not least, the metabolic system of sirtuins, the “longevity proteins” that perceive energy levels and intervene to ensure cell survival in case of severe stress, such as lack of nutrients or lower temperatures.Perché se mangi meno vivi di piùIl calo del rendimento di queste vie metaboliche è un fenomeno fisiologico del tutto normale, ma gli scienziati si sono accorti che la presenza di mutazioni genetiche – in particolare quelle che riguardano l’IGF-1 (Insulin-like Growth Factor-1) – possono cambiare di molto le cose, con un effetto anche sull’aumento della durata della vita e sulla riduzione del rischio di malattie tipiche dell’età.Why eating less implies living longerThe performance decline of these metabolic pathways is a completely normal physiological phenomenon, but scientists have found that the presence of genetic mutations – particularly those involving IGF-1 (Insulin-like Growth Factor-1) – can change things a lot, with an effect also on increasing lifespan and reducing the risk of age-related diseases.

The effect of mutations that mitigate metabolic imbalances typical of ageing can be simulated with calorie restriction.

An interesting aspect of this discovery was to understand that the effect of such mutations can be simulated with caloric restriction, through intermittent fasting patterns or specific diets. There is, in fact, a close link between ageing and metabolic systems designed to capture nutrients.
The insulin receptor (in blue) is a protein which, activated by insulin (in orange), allows glucose to pass from the blood into the cell.
In essence, starving the body for short periods causes a change in metabolism, which leads to better regulation of glucose levels, increased resistance to oxidative stress and suppression of inflammatory processes.

At the moment, caloric restriction is considered the most effective strategy to combat metabolic changes related to ageing and to prevent the accompanying pathological conditions.

Gli effetti della restrizione calorica variano molto in base al genere e all’età. Tuttavia al momento gli esperti sono concordi nel considerarla la strategia più convincente per contrastare i cambiamenti metabolici connessi all’invecchiamento e prevenire le condizioni patologiche che lo accompagnano, dall’ipertensione alle malattie cardiovascolari ai tumori.Non è un caso che le popolazioni che per tradizione seguono un regime alimentare con poche calorie, come gli abitanti di Okinawa in Giappone, mostrino una longevità fuori dal comune e una bassa incidenza di obesità diabete. ‍ Il digiuno intermittente è l’unica soluzione? No: negli ultimi anni si sono accumulate evidenze scientifiche sugli effetti di alcune molecole di origine naturale che possono “mimare” la restrizione calorica andando ad agire proprio su quei meccanismi molecolari che rallentano l’invecchiamento cellulare. Si chiamano “caloric restriction mimetics” (CMRs) e sono in fase di attenta valutazione da parte dei ricercatori perché, essendo presenti nella nostra alimentazione da sempre, non hanno apparenti rischi di tossicità o effetti collaterali. SoLongevity è impegnata nella ricerca di CMRs attivi sulle tre vie metaboliche dell’invecchiamento.The caloric restriction effects vary greatly according to gender and age. However, experts currently agree that it is the most convincing strategy to counteract the metabolic changes associated with ageing and prevent the pathological conditions that accompany it, from hypertension to cardiovascular diseases and tumours.It is no coincidence that people who traditionally follow a low-calorie diet, such as the inhabitants of Okinawa in Japan, show an uncommon longevity and a low incidence of obesity and diabetes.Is intermittent fasting the only solution? No: in recent years scientific evidence has been collected on the effects of certain molecules of natural origin that can “mimic” caloric restriction by acting on those very molecular mechanisms that slow down cellular aging. They are called “caloric restriction mimetics” (CMRs) and are being carefully evaluated by researchers because, being present in our diet since ever, they have no apparent risk of toxicity or side effects. SoLongevity is engaged in the research of active CMRs on the three metabolic pathways of aging.

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