Influence of Blood Flow Restriction on Neuromuscular Function and Fatigue During Forearm Flexion in Men.

ABSTRACT: Montgomery, TR Jr, Olmos, A, Sears, KN, Succi, PJ, Hammer, SM, Bergstrom, HC, Hill, EC, Trevino, MA, and Dinyer-McNeely, TK. Influence of blood flow restriction on neuromuscular function and fatigue during forearm flexion in men. J Strength Cond Res 38(7): e349-e358, 2024-To determine the effects of blood flow restriction (BFR) on the mean firing rate (MFR) and motor unit action potential amplitude (MUAPAMP) vs. recruitment threshold (RT) relationships during fatiguing isometric elbow flexions. Ten men (24.5 ± 4.0 years) performed isometric trapezoidal contractions at 50% maximum voluntary contraction to task failure with or without BFR, on 2 separate days. For BFR, a cuff was inflated to 60% of the pressure required for full brachial artery occlusion at rest. During both visits, surface electromyography was recorded from the biceps brachii of the dominant limb and the signal was decomposed. A paired-samples t test was used to determine the number of repetitions completed between BFR and CON. ANOVAs (repetition [first, last] × condition [BFR, CON]) were used to determine differences in MFR vs. RT and MUAPAMP vs. RT relationships. Subjects completed more repetitions during CON (12 ± 4) than BFR (9 ± 2; p = 0.012). There was no significant interaction (p > 0.05) between the slopes and y-intercepts during the repetition × condition interaction for MUAPAMP vs. MFR. However, there was a main effect of repetition for the slopes of the MUAPAMP vs. RT (p = 0.041) but not the y-intercept (p = 0.964). Post hoc analysis (collapsed across condition) indicated that the slopes of the MUAPAMP vs. RT during the first repetition was less than the last repetition (first: 0.022 ± 0.003 mv/%MVC; last: 0.028 ± 0.004 mv/%MVC; p = 0.041). Blood flow restriction resulted in the same amount of higher threshold MU recruitment in approximately 75% of the repetitions. Furthermore, there was no change in MFR for either condition, even when taken to task failure. Thus, BFR training may create similar MU responses with less total work completed than training without BFR.

Does Box Height Matter? A Comparative Analysis of Box Height on Box Jump Performance in Men and Women.

This study aimed to analyze the effect of box height on box jump performance among recreationally active college students. Fourteen males (age = 20.8 ± 4.1 years, height = 178.3 ± 6.3 cm, weight = 82.3 ± 13.0 kg) and seventeen females (age = 20.8 ± 2.1 years, height = 167.1 ± 5.5 cm, weight = 64.5 ± 7.4 kg) completed box jumps at five different box heights that corresponded to 0, 20, 40, 60, and 80% of their maximal box jump height. Variables of interest included peak force, rate of force development, peak rate of force development, peak power, velocity at peak power, jump height, time to take-off, and reactive strength index modified. Peak force at 80% maximal box jump was significantly higher than 0% in the female cohort (p = 0.001). No significant differences for any of the other variables were observed in males, or at any other height lower than the 80% maximal box jump height for females (p > 0.05). Overall, variations in box height did not influence box jump performance in recreationally trained individuals when the intent to perform a maximal-effort jump was emphasized. This is important for strength and conditioning coaches and trainers, as they can utilize boxes of varied heights when teaching proper landing techniques to novice athletes with no decrements in propulsive performance.

Caloric Restriction Improves Spatial Learning Deficits in Tau Mice.

Background: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results: CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions: Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.

Sex differences in muscle contraction-induced limb blood flow limitations.

PURPOSE: To determined sex differences in absolute- and %-reductions in blood flow during intermittent muscular contractions as well as relationships between blood flow reductions and time to task failure (TTF). METHODS: Thirteen males (25 ± 4 years) and 13 females (22 ± 5 years) completed intermittent isometric trapezoidal forearm flexion at 50% maximal voluntary contraction until task failure. Doppler ultrasound was used to measure brachial artery blood flow (BABF) during the 12-s plateau phase and 12-s relaxation phase. RESULTS: Target torque was less in females than males (24 ± 5 vs. 42 ± 7 Nm; p < 0.001); however, TTF was not different between sexes (F: 425 ± 187 vs. M: 401 ± 158 s; p = 0.72). Relaxation-phase BABF at end-exercise was less in females than males (435 ± 161 vs. 937 ± 281 mL/min; p < 0.001) but contraction-phase BABF was not different (127 ± 46 vs. 190 ± 99 mL/min; p = 0.42). Absolute- and %-reductions in BABF by contraction were less in females than males (309 ± 146 vs. 747 ± 210 mL/min and 69 ± 10 vs. 80% ± 6%, respectively; both p < 0.01) and were associated with target torque independent of sex (r = 0.78 and 0.56, respectively; both p < 0.01). Absolute BABF reduction per target torque (mL/min/Nm) and TTF were positively associated in males (r = 0.60; p = 0.031) but negatively associated in females (r = - 0.61; p = 0.029). CONCLUSIONS: This study provides evidence that females incur less proportional reduction in limb blood flow from muscular contraction than males at a matched relative intensity suggesting females may maintain higher levels of muscle oxygen delivery and metabolite removal than males across the contraction-relaxation cycle of intermittent exercise.

Responses to Exercise at the Critical Heart Rate vs. the Power Output Associated With the Critical Heart Rate.

ABSTRACT: Succi, PJ, Dinyer-McNeely, TK, Voskuil, CC, Abel, MG, Clasey, JL, and Bergstrom, HC. Responses to exercise at the critical heart rate vs. the power output associated with the critical heart rate. J Strength Cond Res 37(12): 2362-2372, 2023-This study examined the physiological (volume of oxygen consumption [V̇ o2 ], heart rate [HR], power output [PO], respiration rate [RR], muscle oxygen saturation [%SmO 2 ]), neuromuscular (electromyographic and mechanomyographic amplitude [EMG AMP and MMG AMP] and mean power frequency [EMG MPF and MMG MPF]), and perceptual (rating of perceived exertion [RPE]) responses during exercise anchored at the critical heart rate (CHR) vs. the PO associated with CHR (PCHR). Nine subjects (mean ± SD ; age = 26 ± 3 years) performed a graded exercise test and 4 constant PO trials to exhaustion at 85-100% of peak PO (PP) to derive CHR and PCHR on a cycle ergometer. Responses were recorded during trials at CHR (173 ± 9 b·min -1 , time to exhaustion [T Lim ] = 45.5 ± 20.2 minutes) and PCHR (198 ± 58 W, T Lim = 21.0 ± 17.8 minutes) and normalized to their respective values at PP in 10% intervals. There were significant ( p ≤ 0.05) mode (CHR vs. PCHR) × time (10%-100% T Lim ) interactions for all variables ( p < 0.001-0.036) except MMG AMP ( p > 0.05). Post hoc analyses indicated differences across time for CHR V̇ o2 (%change = -22 ± 16%), PCHR V̇ o2 (19 ± 5%), CHR RR (24 ± 23%), PCHR RR (45 ± 14%), CHR PO (-33 ± 11%), PCHR HR (22 ± 5%), CHR RPE (22 ± 14%), PCHR RPE (39 ± 6%), CHR %SmO 2 (41 ± 33%), PCHR %SmO 2 (-18 ± 40%), CHR EMG AMP (-13 ± 15%), PCHR EMG AMP (13 ± 13%), CHR EMG MPF (9 ± 8%), CHR MMG MPF (7 ± 11%), and PCHR MMG MPF (-3 ± 14%). The critical heart rate was more sustainable than PCHR but required adjustments in PO which traversed intensity domains and caused dissociations of the responses previously observed in exercise anchored to PO. These dissociations indicated the demands to exercise varied with anchoring scheme and provides an important consideration for practitioners prescribing endurance exercise.

Electromyographic and mechanomyographic responses of the biceps brachii during concentric and eccentric muscle actions to failure at high and low relative loads.

PURPOSE: This study examined neuromuscular responses of the biceps brachii (BB) for concentric and eccentric muscle actions during bilateral, dynamic constant external resistance (DCER), reciprocal forearm flexions and extensions to failure at high (80% 1 repetition maximum [1RM]) and low (30% 1RM) relative loads. METHODS: Nine women completed 1RM testing and repetitions to failure (RTF) at 30 and 80% 1RM. Electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF) signals were measured from the BB. Analyses included repeated measures ANOVAs (p < 0.05) and post-hoc pairwise comparisons with Bonferroni corrected alpha of p < 0.008 and p < 0.01 for between and within factor pairwise comparisons, respectively. RESULTS: EMG AMP and MPF were significantly greater for concentric than eccentric muscle actions, regardless of load or time. However, time course of change analysis revealed parallel increases in EMG AMP for concentric and eccentric muscle actions during the RTF trials at 30% 1RM, but no change at 80% 1RM. There were significant increases in MMG AMP during concentric muscle actions, but decreases or no change during eccentric muscle actions. EMG and MMG MPF decreased over time, regardless of muscle action type and loading condition. CONCLUSION: The greater EMG AMP and MPF values during concentric compared to eccentric muscle actions may reflect the difference in the efficiency characteristic of these muscle actions. The neuromuscular responses suggested that fatigue may be mediated by recruitment of additional motor units with lower firing rates during concentric muscle actions, and changes in motor unit synchronization during eccentric muscle actions.

Oxytocin prevents dysregulation of the acute stress response and glucocorticoid-induced oxidative stress in chronically isolated prairie voles.

Chronic social isolation can lead to dysregulation of many physiological and psychological processes, including the ability to respond to acute stressors. Previous work in our lab reported that six weeks of social isolation in prairie voles (Microtus ochrogaster) caused increased glucocorticoid levels, oxidative damage, telomere degradation and anhedonia, and that oxytocin treatment prevented all of these changes. Following these results, we investigated how chronic social isolation with and without oxytocin treatment affected glucocorticoid (CORT) and oxidative stress responses to an acute stressor, a 5-min resident-intruder (R-I) test at the end of the social isolation period. To investigate the effect of a brief acute stressor on CORT and oxidative stress, baseline blood samples were collected following six weeks of social isolation, 24-hrs before the R-I test. Two more blood samples were collected 15-min after the end of the R-I test, and again 25-min later to measure peak and recovery responses, respectively. Isolated animals had higher baseline, peak, recovery, and integrated levels of CORT and reactive oxygen metabolites (ROMs, a measure of oxidative stress), compared to animals that did not experience isolation. Importantly, oxytocin treatment throughout the isolation period prevented these elevations in CORT and ROMs. No significant changes were observed in total antioxidant capacity (TAC). Levels of CORT and ROMs at the peak and recovery time points were positively correlated. These data show that acute stress in chronically isolated prairie voles, then, is associated with increased glucocorticoid-induced oxidative stress (GiOS), and that oxytocin mitigates isolation-induced dysregulation of glucocorticoid and oxidative stress acute stress responses.

The response to stressors in adulthood depends on the interaction between prenatal exposure to glucocorticoids and environmental context.

Maternal stress during reproduction can influence how offspring respond to stress later in life. Greater lifetime exposure to glucocorticoid hormones released during stress is linked to greater risks of behavioral disorders, disease susceptibility, and mortality. The immense variation in individual's stress responses is explained, in part, by prenatal glucocorticoid exposure. To explore the long-term effects of embryonic glucocorticoid exposure, we injected Japanese quail (Coturnix japonica) eggs with corticosterone. We characterized the endocrine stress response in offspring and measured experienced aggression at three different ages. We found that prenatal glucocorticoid exposure affected (1) the speed at which the stress response was terminated suggesting dysregulated negative feedback, (2) baseline corticosterone levels in a manner dependent on current environmental conditions with higher levels of experienced aggression associated with higher levels of baseline corticosterone, (3) the magnitude of an acute stress response based on baseline concentrations. We finish by proposing a framework that can be used to test these findings in future work. Overall, our findings suggest that the potential adaptive nature of prenatal glucocorticoid exposure is likely dependent on environmental context and may also be tempered by the negative effects of longer exposure to glucocorticoids each time an animal faces a stressor.

Load-Specific Performance Fatigability, Coactivation, and Neuromuscular Responses to Fatiguing Forearm Flexion Muscle Actions in Women.

ABSTRACT: Benitez, B, Dinyer-McNeeley, TK, McCallum, L, Kwak, M, Succi, PJ, and Bergstrom, HC. Load-specific performance fatigability, coactivation, and neuromuscular responses to fatiguing forearm flexion muscle actions in women. J Strength Cond Res 37(4): 769-779, 2023-This study examined the effects of fatiguing, bilateral, dynamic constant external resistance (DCER) forearm flexion on performance fatigability, coactivation, and neuromuscular responses of the biceps brachii (BB) and triceps brachii (TB) at high (80% 1 repetition maximum [1RM]) and low (30% 1RM) relative loads in women. Ten women completed 1RM testing and repetitions to failure (RTF) at 30 and 80% 1RM. Maximal voluntary isometric force was measured before and after RTF. Electromyographic (EMG) and mechanomyographic (MMG) amplitude (AMP) and mean power frequency (MPF) signals were measured from the BB and TB. Performance fatigability was greater (p < 0.05) after RTF at 30% (%∆ = 41.56 ± 18.61%) than 80% (%∆ = 19.65 ± 8.47%) 1RM. There was an increase in the coactivation ratio (less coactivation) between the initial and final repetitions at 30%, which may reflect greater increases in agonist muscle excitation (EMG AMP) relative to the antagonist for RTF at 30% than 80% 1RM. The initial repetitions EMG AMP was greater for 80% than 30% 1RM, but there was no difference between loads for the final repetitions. For both loads, there were increases in EMG MPF and MMG AMP and decreases in MMG MPF that may suggest fatigue-dependent recruitment of higher-threshold motor units. Thus, RTF at 30 and 80% 1RM during DCER forearm flexion may not necessitate additional muscle excitation to the antagonist muscle despite greater fatigability after RTF at 30% 1RM. These specific acute performance and neuromuscular responses may provide insight into the unique mechanism underlying adaptations to training performed at varying relative loads.

Differences and Relationships Between Push-up and Sit-up Variations Among Male Law Enforcement Cadets.

ABSTRACT: Lopes dos Santos, M, Thompson, M, Dinyer-McNeely, T, Torrence, T, Lockie, RG, Orr, RM, and Dawes, JJ. Differences and relationships between push-up and sit-up variations among male law enforcement cadets. J Strength Cond Res 37(9): 1865-1869, 2023-The purpose of this study was to explore variation-dependent differences in push-up and sit-up tests, as well as to identify the relationships between push-up and sit-up variations commonly performed among tactical personnel. Data from 41 (age = 21.1 ± 1.8 years, body mass = 89.5 ± 15.5 kg) male police cadets from one US-based training academy who performed the standard push-up (PU Standard ), hand-release push-up (PU Hand-release ), standard sit-up (SU Standard ), and hands behind the head sit-up (SU BehindHead ) were examined. The maximum number of repetitions completed for each exercise was used for analyses with paired-samples t tests used to identify significant differences between outcome measures and effect sizes (ES) to determine change in magnitude. A significant difference, with a large ES, was found in the number of repetitions completed between the push-up variations ( p < 0.001, ES = 0.75) and sit-up variations ( p < 0.001, ES = 1.02). Performance in PU Standard was only able to explain 39% of the variation in PU Hand-release ( r = 0.62, r2 = 0.39, p < 0.001), and performance in the SU Standard was only able to explain 29% of the variation in SU BehindHead ( r = 0.54, r2 = 0.29, p < 0.001). The current study suggests differences in performance capabilities may be dependent on the push-up and sit-up variations chosen for testing. Although it is still unclear whether one variation would be a better predictor of police work performance, agencies must give special attention to the overall construct validity of fitness tests for entry and retention of law enforcement officers.

Untangling senescent and damage-associated microglia in the aging and diseased brain.

Microglial homeostasis has emerged as a critical mediator of health and disease in the central nervous system. In their neuroprotective role as the predominant immune cells of the brain, microglia surveil the microenvironment for debris and pathogens, while also promoting neurogenesis and performing maintenance on synapses. Chronological ageing, disease onset, or traumatic injury promotes irreparable damage or deregulated signaling to reinforce neurotoxic phenotypes in microglia. These insults may include cellular senescence, a stable growth arrest often accompanied by the production of a distinctive pro-inflammatory secretory phenotype, which may contribute to age- or disease-driven decline in neuronal health and cognition and is a potential novel therapeutic target. Despite this increased scrutiny, unanswered questions remain about what distinguishes senescent microglia and non-senescent microglia reacting to insults occurring in ageing, disease, and injury, and how central the development of senescence is in their pivot from guardian to assailant. To intelligently design future studies to untangle senescent microglia from other primed and reactionary states, specific criteria must be developed that define this population and allow for comparisons between different model systems. Comparing microglial activity seen in homeostasis, ageing, disease, and injury allows for a more coherent understanding of when and how senescent and other harmful microglial subpopulations should be targeted.

Affective and Perceptual Responses During an 8-Week Resistance Training to Failure Intervention at Low vs. High Loads in Untrained Women.

ABSTRACT: Anderson, AlOK, Voskuil, CC, Byrd, MT, Garver, MJ, Rickard, AJ, Miller, WM, Bergstrom, HC, and Dinyer McNeely, TK. Affective and perceptual responses during an 8-week resistance training to failure intervention at low vs. high loads in untrained women. J Strength Cond Res 37(3): 546-554, 2023-This study examined the effects of resistance training (RT) to failure on the perceptual and affective responses, intent-to-continue RT to failure in a self-initiated session, and affect-intent relationship. Twenty-three untrained women (mean ± SD : age 21.2 ± 2.2 years; height 167 ± 5.7 cm; body mass, 62.3 ± 16.2 kg) completed an 8-week, full-body RT to failure intervention at a low (30% 1RM; n = 11) or high (80% 1RM; n = 12) load. The Borg's rating of perceived exertion (RPE) scale was used to assess the acute (aRPE) and session (sRPE) RPE immediately after repetition failure and each training session, respectively. Immediately, 15-minute, and 60-minute postsession affective responses were assessed using the feeling scale (FS; -5 to +5), and intent to continue to RT was assessed on a scale of 0-100% intention. During week 4 (W4) and week 8 (W8), aRPE (W4: 18 ± 2, W8: 18 ± 2; p ≤ 0.032) and sRPE (W4: 17 ± 2, W8: 18 ± 1; p ≤ 0.018) were greater than that during week 1 (W1; aRPE: 17 ± 2; sRPE: 16 ± 2). The FS responses increased from immediately to 60-minute postsession during W4 ( p ≤ 0.019) and W8 ( p ≤ 0.049). The correlation between affect and intent-to-continue RT increased from W1 ( r = 0.416) to W8 ( r = 0.777). Regardless of load, untrained women reported similar perceptual, affective, and intention responses. These variables should be considered to improve RT program adoption and adherence in women.

Unilateral Handgrip Holds to Failure Result in Sex-Dependent Contralateral Facilitation.

This study examined changes in maximal voluntary isometric contraction (MVIC) force following dominant (Dm) and nondominant (NDm) unilateral, handgrip isometric holds to failure (HTF) for the exercised ipsilateral (IPS) and non-exercised contralateral (CON) limbs and determined if there are sex- and hand- (Dm vs NDm) dependent responses in the HTF time, performance fatigability (PF) for the exercised IPS limb, and changes in MVIC force for the CON limb after unilateral fatigue. Ten men and 10 women (Age = 22.2 years) completed an isometric HTF at 50% MVIC for the Dm and NDm hand on separate days. Prior to, and immediately after the HTF, an MVIC was performed on the IPS and CON limbs, in a randomized order. The Dm (130.3 ± 36.8 s) HTF (collapsed across sex) was significantly longer (p = 0.002) than the NDm (112.1 ± 34.3 s). The men (collapsed across hand) demonstrated IPS (%Δ = 22.9 ± 10.8%) PF and CON facilitation (%Δ = -6.1 ± 6.9%) following the HTF, while the women demonstrated differences in PF between the Dm and NDm hands for the IPS (%Δ Dm = 28.0 ± 9.4%; NDm = 32.3% ± 10.1%; p = 0.027), but not the CON limb (%Δ Dm = -1.6 ± 5.7%; NDm = 1.7 ± 5.9%). The cross-over facilitation of the CON limb for men, but not women, following a unilateral, isometric handgrip HTF may be related to post-activation potentiation.

Male rat leukocyte population dynamics predict a window for intervention in aging.

Many age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from 3 to 27 months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25+ CD4+ population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions. Importantly, blood parameters and DNA methylation alterations, defined distinct juncture points during aging, supporting a non-linear aging process. Our results suggest these inflection points are important considerations for aging interventions. Overall, we present rat blood aging metrics that can serve as a resource to evaluate health and the effects of interventions in a model system physiologically more reflective of humans.

Our blood contains many types of white blood cells, which play important roles in defending the body against infections and other threats to our health. The number of these cells changes with age, and this in turn contributes to many other alterations that happen in the body as we get older. For example, the immune system generally gets weaker at fighting infections and preventing other cells from developing into cancer. On top of that, the white blood cells themselves can become cancerous, resulting in several types of blood cancer that are more likely to happen in older people. Many previous studies have examined how the number of white blood cells changes with age in humans and mice. However, our understanding of this process in rats is still poor, despite the fact that the way the human body works has more in common with the rat body than the mouse body. Here, Yanai, Dunn et al. have studied samples of blood from rats between three to 27 months old. The experiments found that it is possible to accurately predict the age of healthy rats by measuring the frequency of populations of white blood cells, especially a certain type known as CD25+ CD4+ cells. If the animals had any form of illness, their predicted age deviated from their actual age. Furthermore, while some changes in the blood were gradual and continuous, others displayed distinct shifts when the rats reached specific ages. In the future, these findings may be used as a tool to help researchers diagnose illnesses in rats before the animals develop symptoms, or to more easily establish if a treatment is having a positive effect on the rats' health. The work of Yanai, Dunn et al. also provides new insights into aging that could potentially aid the design of new screening methods to predict cancer and intervene using a model system that is more similar to humans.

DNA damage in aging, the stem cell perspective.

DNA damage is one of the most consistent cellular process proposed to contribute to aging. The maintenance of genomic and epigenomic integrity is critical for proper function of cells and tissues throughout life, and this homeostasis is under constant strain from both extrinsic and intrinsic insults. Considering the relationship between lifespan and genotoxic burden, it is plausible that the longest-lived cellular populations would face an accumulation of DNA damage over time. Tissue-specific stem cells are multipotent populations residing in localized niches and are responsible for maintaining all lineages of their resident tissue/system throughout life. However, many of these stem cells are impacted by genotoxic stress. Several factors may dictate the specific stem cell population response to DNA damage, including the niche location, life history, and fate decisions after damage accrual. This leads to differential handling of DNA damage in different stem cell compartments. Given the importance of adult stem cells in preserving normal tissue function during an individual's lifetime, DNA damage sensitivity and accumulation in these compartments could have crucial implications for aging. Despite this, more support for direct functional effects driven by accumulated DNA damage in adult stem cell compartments is needed. This review will present current evidence for the accumulation and potential influence of DNA damage in adult tissue-specific stem cells and propose inquiry directions that could benefit individual healthspan.