It’s natural to worry about the effects of aging on our bodies and minds. But there’s hope in recent scientific progress, especially in the area of anti-aging. Scientists have been working on pills that target mitochondria, the tiny powerhouses within our cells, to potentially slow down the aging process.

Understanding aging and mitochondria

Anti-aging pills based on mitochondrial rejuvenation?

Aging involves a gradual decline in both our physical and mental abilities. One important part of this process is the mitochondria, often called the “powerhouse of the cell.” These tiny structures are in charge of making energy in the form of ATP through a process called oxidative phosphorylation. But as we get older, this process becomes less efficient. That means we make less energy and produce more harmful substances called reactive oxygen species (ROS), which can harm cells. Scientists call this the mitochondrial theory of aging.

For instance, studies have found that in diseases like Alzheimer’s and Parkinson’s, which are linked to getting older, there’s a big drop in how well mitochondria work. So, figuring out how mitochondria are involved in aging is really important for finding ways to treat age-related diseases.

The role of mitochondria in aging

As we age, our mitochondria can start to malfunction. This happens because of things like DNA mutations and increased levels of harmful substances called reactive oxygen species. This damage to mitochondria can speed up the aging process. And our body’s defense system, called the immune system, gradually gets weaker. In scientific terms, this natural aging process is referred to as immunosenescence. One reason for this decline is that mitochondria don’t work well.

Research has shown that as people age, their immune cells have fewer mitochondria. This means our immune system then might not work as effectively, which can make us more likely to get sick.

Anti-aging pills based on mitochondrial rejuvenation?
Mitochondrial damage associated molecular patterns (DAMPs). DAMPs derived from mitochondrial components may be released during cellular injury, apoptosis or necrosis. Once these mitochondrial components are released into the extracellular space, they can lead to the activation of innate and adaptive immune cells. The recognition of mitochondrial DAMPs involves toll-like receptors (TLR), formyl peptide receptors (FPR) and purigenic receptors (P2RX7). By binding their cognate ligands or by direct interaction (i.e., reactive oxygen species, ROS), intracellular signaling pathways such as NFkB and the NLRP3 inflammasome become activated resulting in a proinflammatory response. TLR4 = toll-like receptor 4, TLR9 = toll-like receptor 9, P2RX7 = purigenic receptor, FPR1 = formyl peptide receptor 1, NLRP3 = NLR Family Pyrin Domain Containing 3, fMet = N-formylmethionine, mtROS = mitochondrial reactive oxygen species, mtDNA = mitochondrial DNA, Tfam = transcription factor A, mitochondrial, RAGE = receptors for advanced glycation end-products, NFkB = nuclear factor kappa-light-chain-enhancer of activated B cells. Description/Image Credit: National Library of Medicine

So, taking care of our mitochondria could be really important for keeping our immune system strong as we age. That’s where mitochondrial rejuvenation comes in. By boosting the function of our mitochondria, we might be able to improve our immune response, even as we get older.

Mitochondrial rejuvenation as an anti-aging strategy

Mitochondrial rejuvenation is an exciting area of research in anti-aging treatments. The idea behind this is to fix and improve how mitochondria work to fight the effects of getting older.

Scientists, for example, are looking into certain substances that might boost how mitochondria function. One of these is Nicotinamide Adenine Dinucleotide (NAD+), which is important for making energy in mitochondria. As we get older, our bodies have less NAD+, which means our mitochondria work less effectively. Giving NAD+ or things that help make it has been proven to make mitochondria work better and improve overall health in older mice.

Anti-aging pills based on mitochondrial rejuvenation?
Successful NAD+ restoration requires a multitargeted strategy that simultaneously addresses the root causes of NAD+ decline. Therapies must reduce the excessive consumption of NAD+ with approaches such as CD38 inhibition and reduction of DNA damage, while improving the efficiency of NAD+ recycling by promoting upregulation of the rate-limiting salvage pathway enzyme NAMPT and inhibition of NNMT, an enzyme that promotes the removal of NAD+ breakdown products from the cell rather than recycling. Description/Image Credit: NLM

Another possible idea would be to use antioxidants that target mitochondria. These substances can stop harmful chemicals made by mitochondria, which can damage cells and maybe slow down aging.

Also, scientists are studying stem cells for mitochondrial rejuvenation.

Anti-aging pills based on mitochondrial rejuvenation?
Different ways and protective mechanisms of mesenchymal stem cell mitochondrial transfer to damaged cells. Pathways by which healthy mitochondria are transferred from stem cells to mitochondrial dysfunction receptor cells include TNT formation, release of extracellular vesicles, and mitochondrial extrusion. Exosomes may transfer organelle fragments (such as protein complexes of mitochondrial electron transfer chains), mtDNA and ribosomes. Miro, mitochondrial Rho-GTPase1; TNT, tunneling nanotube; Drp 1, dynamin-related protein 1. Description Credit: NLM; Image Credit: BioRender.com

Stem cells can make more of themselves and turn into different types of cells, and their mitochondria seem to work better than those in other cells. So, treatments that involve putting stem cells or their mitochondria into older tissues and organs might make them younger again.

These are just a few examples of what researchers are looking into to rejuvenate mitochondria. Even though we’re still early in this research, the future of anti-aging treatments looks bright with these ideas.

The future of anti-aging pills

Indeed, the outlook for anti-aging treatments focusing on mitochondria appears promising. For example, research indicates that using substances like Coenzyme Q10, an antioxidant supporting mitochondrial function, can enhance the health and lifespan of mice.

Short-term plasticity in the motor cortex was not affected by age or CoQ10 supplementation. (a) Paired pulse ratios (PPRs) at various stimulus intervals (25, 50, 100, 200, and 500 ms) were comparable in the M1 region (young adult, n = 14 slices from 5 mice; middle-aged, n = 27 slices from 9 mice) and the M2 region (young adult, n = 9 slices from 4 mice; middle-aged, n = 24 slices from 10 mice; no significant difference by age). (b) CoQ10 supplementation did not alter the PPRs in the M1 or M2 regions of middle-aged mice compared to those of the age-matched controls (M1: middle-aged + CoQ10, n = 8 slices from 4 mice; middle-aged, n = 27 slices from 9 mice; M2: middle-aged + CoQ10, n = 12 slices from 5 mice; middle-aged, n = 24 slices from 10 mice; no significant differences with supplementation). The middle-aged control data in (b) are identical to those in (a). Values are expressed as the mean ± SEM of independent experimental groups. Statistical analyses were performed using two-way repeated-measures ANOVA. Description/Image Credit: nature.com

Similarly, trials involving humans and supplements like Nicotinamide Riboside, a precursor of NAD+ crucial for mitochondrial energy production, have displayed potential advantages in bolstering mitochondrial health and decelerating aging.

Anti-aging pills based on mitochondrial rejuvenation?
NR promotes muscle satellite cell differentiation in the twins from the BMI-discordant pairs. (A) Muscle gene expression level of satellite cell marker PAX7 before versus after NR (n = 9 twin pairs/18 individuals). (B) Immunostaining of PAX7+ satellite cells in muscle cryosections before versus after NR in one representative study participant. PAX7 (red, satellite cells); Hoechst (blue, nuclei). Scale bars, 10 μm. (C) Muscle PAX7+ satellite cell quantification before versus after NR (n = 10 twin pairs/20 individuals). (D to G) Ratios of PAX7/MYOG (D), PAX3/MYOG (E), MYF5/MYOD (F), and MYMK/MYOD (G) mRNA expression in myoblasts before versus after NR (n = 3 twin pairs/6 individuals). Y axis is on a logarithmic scale. PAX3, paired box 3; MYF5, myogenic factor 5. Lines connect the pre- and post-values of each individual, with black denoting the leaner and red denoting the heavier cotwins. Fold change indicates the mean of the post-NR value divided by the pre-NR value. P values were calculated using paired Wilcoxon signed-rank test. Description/Image Credit: science.org

In addition, technological advancements, such as the creation of nanocarriers for targeted delivery of drugs to mitochondria, are opening doors to more efficient therapies. These innovations have the potential to refine the precision and effectiveness of anti-aging treatments, offering hope not only for slowing down aging but even potentially reversing it.

References:

https://www.nature.com/articles/s41392-023-01343-5
https://www.nature.com/articles/s43587-022-00340-7
https://www.nature.com/articles/s41598-023-31510-1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627503/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773271/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512238/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519729/
https://www.science.org/doi/10.1126/sciadv.add5163
https://pubs.rsc.org/en/content/articlehtml/2024/ma/d3ma00629h

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