LongeCityNews Last Updated: 12 March 2026 - 10:31 AM

Mitochondria are the power plants of the cell, vital to cell and tissue function. Mitochondria become damaged and dysfunctional with age, unfortunately, and this is thought to be a major contribution to age-related degeneration. That cells will take up mitochondria from the surrounding environment and put them to use has been established for some years. It is the basis for the development of mitochondrial transplantation therapies as a way to improve cell function in old tissues, delivering youthful mitochondria to augment the activities of native mitochondria that have been impaired by mechanisms of aging. Meanwhile, the research community continues to explore how exactly cells achieve uptake of mitochondria, as greater knowledge of the details may lead to ways to significantly improve on the coming first generation of mitochondrial transplantation therapies.

In today's open access paper, researchers report results from their study of how exactly the processes of endocytosis can be used to ingest mitochondria while preserving their structure and function. As a mitochondrion comes into contact with the exterior of the cell membrane, a region of the membrane wraps around the mitochondrion and then breaks off to bring it inside the cell, wrapped in an endosome. At some point the endosome is removed and the mitochondrion is fully internalized, intact and able to contribute to cell metabolism. This is a very high level description; there are a number of functionally distinct forms of endocytosis, and it appears that different types of endocytosis are used interchangeably for mitochondrial uptake, making it a more robust behavior.

Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells

Mitochondrial transplantation holds great promise as a therapeutic strategy; however, the mechanisms by which recipient cells interact with and internalize isolated mitochondria remain unclear. Therefore, in this study, we isolated functional mitochondria from mesenchymal stromal cells (MSCs) and characterized their biological activities and physicochemical properties. Additionally, effects of isolated mitochondria on MSC functions were evaluated.

Treatment with isolated mitochondria promoted cell proliferation, improved cellular viability under stress conditions, and increased the oxygen consumption rate, indicating enhanced bioenergetic capacity. Uptake of isolated mitochondria by MSCs was visualized via fluorescence imaging and quantitatively assessed over time, showing progressive internalization within 24 hours. To investigate the mechanism of mitochondrial uptake, endocytosis was chemically inhibited, which revealed that endocytic pathways contributed to the internalization of the isolated mitochondria.

These findings suggest that MSCs incorporate isolated mitochondria via active uptake mechanisms and that the internalized mitochondria retain their functional activity. Collectively, our results provide critical evidence of mitochondrial internalization in MSCs and offer insights into the potential applications of mitochondrial therapy for various diseases.

A recent study published in Geriatrics debunks the assumption that an older chronological age results in an inevitable and universal decline in health. The researchers reported that a significant number of older adults who participated in the study experienced an improvement in cognitive and/or physical functioning [1].

Challenging the status quo

Older age is known as a time of decline in both physical and cognitive health. Surveys have found that the vast majority of the general population, as well as health professionals, wrongly believe that everyone will develop dementia or that, as they age, their cognitive abilities will decline [2]. Even the tools used by the World Health Organization (WHO) to measure later-life cognitive and physical health only show whether there is or isn’t a decline, without the option for improvement [3].

Beyond not considering improvement as a possible outcome, there is also another reason the health improvements at older ages are not widely reported: researchers most often use average values to represent trajectories, and people who experienced improvements, if they are in the minority, do not show up in the results. “What’s striking is that these gains disappear when you only look at averages,” said lead author Becca R. Levy, a professor of social and behavioral sciences at the Yale School of Public Health (YSPH). “If you average everyone together, you see decline. But when you look at individual trajectories, you uncover a very different story.” Additionally, if some individuals show visible improvements, they are often viewed as exceptions rather than as part of a broader pattern [2].

The overall results perpetuates the idea that chronological aging leads to inevitable decline. However, this study challenges that assumption and presents evidence that improvement is possible, even at an older age.

Beyond extraordinary people

To give examples in support of the possibility of late-age improved performance, the authors start their paper with examples of people who achieved their biggest life achievements in later life, such as Diana Nyad, who, despite earlier failed attempts, at the ripe age of 64, set a world record in the 110-mile swim from Cuba to Florida.

Such anecdotes may lead to a conclusion that only very special, gifted individuals can improve with age. Therefore, these researchers analyzed data from a nationally representative Health and Retirement Study (HRS) of participants aged 65 and older to investigate whether improvement is possible even for the average person and “whether positive age beliefs predicted this potential improvement”.

In this study, physical health was assessed in almost 5,000 participants using walking speed, and global performance measures of cognitive health were collected in over 11,000 participants using a test that covers a broad range of cognitive domains, including short-term memory, delayed recall, and mathematical skills. The measures were taken at the beginning of the study and during follow-ups up to 12 years.

The power of belief

When the researchers in this study analyzed the study participants as a single homogeneous group, they observed, on average, declines in cognitive function and walking speed. However, upon closer, more granular examination, the researchers reported that, when analyzing a smaller subset of participants (those who had measurements of both walking speed and cognition), over 45% showed improved levels of cognitive and/or physical functioning beyond baseline, with many showing improvement in both domains. When analyzed separately, almost 32% of participants improved their cognition, and 28% improved their walking speed. A similar pattern of results was seen even with more stringent criteria.

Improvement in cognitive and physical health was predicted by the study participants’ positive age-related beliefs, even after adjusting for various factors and when more stringent criteria were applied to the analysis. Positive age beliefs associated with improvements were observed not only in participants who had some deficits at the beginning of the study (and were recovering from them) but also among people who had normal levels of functioning and improved beyond those levels.

In line with these results are the results of a previous study from this group that showed an association between negative age-related beliefs and biomarkers of Alzheimer’s disease, such as plaque and tangle accumulation, as well as lower hippocampal volume [4]. However, future studies should examine whether such an association exists between positive age-related beliefs and biomarkers of improved brain functioning, such as neurogenesis.

These results also agree with the stereotype embodiment theory (SET). According to this theory, the internalization of beliefs about old age begins at a young age and comes from various environmental sources. Those beliefs, when an individual becomes older, not only apply to others but also to oneself and can be used to predict better or worse cognitive and physical health [5].

Contradicting common views

The results of this study “contradict a dominant belief about aging held by scientists, health care professionals, and the lay public that it is a time of inevitable and universal decline in functioning.” This study provides additional evidence in support of previous studies that show a similar pattern, all suggesting that geroscience studies should go beyond investigating the speed of decline and also consider the possibility of improvements [6-8].

“Many people equate aging with an inevitable and continuous loss of physical and cognitive abilities,” said Levy. “What we found is that improvement in later life is not rare, it’s common, and it should be included in our understanding of the aging process.”

“Our findings suggest there is often a reserve capacity for improvement in later life,” she said. “And because age beliefs are modifiable, this opens the door to interventions at both the individual and societal level.”

Literature

[1] Levy, B. R., & Slade, M. D. (2026). Aging Redefined: Cognitive and Physical Improvement with Positive Age Beliefs. Geriatrics, 11(2), 28.

[2] Mehegan, L., & Rainville, C. (2023). ADULTS’ UNDERSTANDING OF COGNITIVE DECLINE, DEMENTIA, AND ALZHEIMER’S DISEASE. Innovation in Aging, 7(Suppl 1), 130.

[3] World Health Organization. (2004). Integrated Care for Older People (ICOPE): Guidance for Person-Assessment and Pathways in Primary Care; World Health Organization: Geneva, Switzerland

[4] Levy, B. R., Ferrucci, L., Zonderman, A. B., Slade, M. D., Troncoso, J., & Resnick, S. M. (2016). A culture-brain link: Negative age stereotypes predict Alzheimer’s disease biomarkers. Psychology and aging, 31(1), 82–88.

[5] Levy B. (2009). Stereotype Embodiment: A Psychosocial Approach to Aging. Current directions in psychological science, 18(6), 332–336.

[6] Levy, B. R., Pilver, C., Chung, P. H., & Slade, M. D. (2014). Subliminal Strengthening: Improving Older Individuals’ Physical Function Over Time With an Implicit-Age-Stereotype Intervention: Improving Older Individuals’ Physical Function Over Time With an Implicit-Age-Stereotype Intervention. Psychological Science, 25(12), 2127-2135.

[7] Meisner B. A. (2012). A meta-analysis of positive and negative age stereotype priming effects on behavior among older adults. The journals of gerontology. Series B, Psychological sciences and social sciences, 67(1), 13–17.

[8] Westerhof, G. J., Nehrkorn-Bailey, A. M., Tseng, H.-Y., Brothers, A., Siebert, J. S., Wurm, S., Wahl, H.-W., & Diehl, M. (2023). Longitudinal effects of subjective aging on health and longevity: An updated meta-analysis. Psychology and Aging, 38(3), 147–166.

A number of existing classes of drug are suspected to be geroprotective to some degree, altering metabolism in ways that either reduce ongoing cell and tissue damage or help to resist some of the consequences of that damage. We should expect effects on life span at established doses to be modest at best, but there is always the question of how large an effect on human life span can remain hidden because no-one was looking all that hard for it. Here, researchers present evidence for a commonly used PPARα agonist to slow aging in various mouse model. It remains a question as to whether effects in humans are meaningful in comparison to, say, the established benefits of regular exercise.

Aging poses a growing global health burden, creating an urgent need for effective interventions. This study reveals that fenofibrate, a clinically approved drug for hyperlipidemia, exerts significant anti-aging effects by targeting fundamental aging processes. We demonstrated that fenofibrate treatment delays systemic aging in D galactose-induced aging mice, 18-month-old mice, and SAMP8 mice and reverses cellular senescence. Mechanistically, fenofibrate ameliorates age-related lipid accumulation, as evidenced by lipidomic profiling and histological analyses in both cellular and animal models.

Notably, we identify carnitine palmitoyl transferase 1 C (CPT1C) as a crucial mediator of fenofibrate's ability to restore mitochondrial function in senescent cells, as validated by comprehensive metabolic analyses. Fenofibrate is a specific peroxisome proliferator activated receptor α (PPARα) agonist. These effects are mediated through PPARα activation, upregulating downstream metabolic regulators CPT1C. Fenofibrate cannot reverse aging in Pparα knockout mice, establishing that its anti-aging effects are strictly PPARα-dependent.

Our findings demonstrate that fenofibrate delays aging progression of mice and reverses cellular senescence in the PPARα-dependent way. Fenofibrate attenuates lipid accumulation and mitochondrial dysfunction in senescent cells and aged mice by activating the PPARα-CPT1C axis. This research provided the first evidence that pharmacological PPARα activation can directly modulate natural aging through coordinated improvement of lipid metabolism and mitochondrial function. The clinical relevance is underscored by the safety profile and widespread use of fenofibrate, suggesting its immediate potential as a repurposed anti-aging therapeutic. Furthermore, this work establishes PPARα as a master metabolic regulator of aging processes and reveals CPT1C as a novel therapeutic target for age-related metabolic dysfunction.

Link: https://doi.org/10.1016/j.phrs.2026.108154

Periodontitis, the formal name given to inflammatory gum disease, is known to correlate to risk of a range of age-related conditions, including osteoporosis, the loss of bone mass and strength that occurs with age. A number of different mechanisms may be responsible for these correlations, and it remains a matter for debate as to which is most important. In the context of cardiovascular disease, researchers have focused on leakage of oral bacteria and inflammatory metabolites into the circulation via injured gums. Here, in the context of osteoporosis, researchers suggest that the oral bacteria responsible for periodontitis can alter the composition of the gut microbiome in ways that impair bone tissue maintenance, favoring the destruction of bone extracellular matrix by osteoclasts over matrix deposition by osteoblasts.

Epidemiological studies have highlighted an association between periodontitis and osteoporosis. However, the mechanism underlining this association remains unclear. Here, we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients, with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.

Using an ovariectomized (OVX) mouse model, we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota. Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism. The tryptophan metabolite indole-3-lactic acid (ILA) directly inhibited osteoclast formation and differentiation. In OVX mice treated with periodontitis salivary microbiota, supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.

In summary, our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.

Link: https://doi.org/10.1038/s41368-025-00415-2